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Upadacitinib shows positive endoscopic outcomes in Crohn’s disease at 1 year
The findings of this subanalysis come from two phase 3 induction trials (U-EXCEL and U-EXCEED) and one maintenance study (U-ENDURE) of upadacitinib in this patient population.
“Upadacitinib shows large differences relative to placebo in endoscopic response and remission ... in a difficult-to-treat population of patients, the majority of whom had failed an advanced therapy,” lead investigator Brian Feagan, MD, senior scientific director of the GI contract research firm Alimentiv in London, Ontario, said in an interview.
“The absolute magnitude of the finding was unanticipated – a greater treatment effect than might be anticipated for these outcomes compared with other advanced treatments for Crohn’s disease in these higher-risk patients,” he said.
Dr. Feagan presented the research at the annual congress of the European Crohn’s and Colitis Organisation.
Research methodology
At baseline, participants had an average daily stool frequency of 4 or more and/or an abdominal pain score of 2 or greater. They also had a Simple Endoscopic Score for Crohn’s disease of 6 or more, excluding a narrowing component, or a score of 4 or more for isolated ileal Crohn’s disease.
In the treatment induction phase, patients were randomly assigned 2:1, with 674 people receiving 45 mg upadacitinib and 347 taking a placebo once daily for 12 weeks.
Participants who experienced at least a 30% decrease in stool frequency and/or daily abdominal pain scores were enrolled in the maintenance phase of the study. For this phase, patients were randomly assigned again, with 168 receiving 30 mg upadacitinib, 169 receiving 15 mg upadacitinib, and 165 taking a placebo once daily for 52 weeks.
In each induction and maintenance cohort, more than 70% of patients had failed one prior biologic therapy, with failure defined as inadequate response or intolerance. Among those who failed a previous biologic in induction, 96% had also failed prior treatment with an anti–tumor necrosis factor (anti-TNF) inhibitor.
Participants’ mean age was 38-40 years, and 52%-55% were men. Patients who had not failed previous therapy had Crohn’s disease for a median of 6-7 years. In contrast, the prior-failure group had Crohn’s disease for a median of 9-10 years.
Key outcomes
At 12 weeks, endoscopic response among patients who had not failed a prior biologic was 52% in the treatment group versus 16% of the placebo group. In the prior-failure group, endoscopic response was observed in 36% and 5%, respectively.
Endoscopic remission at 12 weeks among patients who had not failed a prior biologic was 36% in the treatment group versus 10% in the placebo group. In the prior-failure group, endoscopic remission was 20% in the treatment group versus 3% in those who took placebo.
Participants in the treatment groups of the 52-week maintenance phase of the study experienced higher endoscopic response and endoscopic remission rates compared with those who received placebo.
Endoscopic response in the group without prior biologic failure was 44% in the 30-mg upadacitinib group, 40% in the 15-mg group, and 18% in the placebo group. Among those with prior biologic failure, endoscopic response was seen in 39% of the 30-mg upadacitinib group, 23% of the 15-mg group, and 4% of the placebo group.
There is a “very striking difference in endoscopic response rates between the high dose and placebo,” Dr. Feagan said. “That difference here is in the response rate. You see dose separation.”
Endoscopic remission among those without prior biologic failure was observed in 34% of the 30-mg upadacitinib group, 27% of the 15-mg group, and 16% of the placebo group. Among those with prior biologic failure, endoscopic remission was seen in 27% of the 30-mg upadacitinib group, 16% of the 15-mg group, and 2% of the placebo group.
The results show “a clear advantage for the 30-mg dose versus the 15-mg in the maintenance component, especially in patients who had failed an advanced therapy,” Dr. Feagan said.
Safety signals
Upadacitinib was well tolerated in the induction and maintenance phases, and no new safety risks were observed compared with the known safety profile of the drug, the researchers noted.
For example, during the induction studies, the rate of any adverse event among patients without prior biologic failure was 60% in the 45-mg upadacitinib group and 53% in the placebo group. Among those who failed a prior biologic, the rates were 67% in the 45-mg upadacitinib group and 66% in the placebo group.
The adverse events were “issues that have already been identified with JAK inhibitors, the biochemical abnormalities with CPK [creatine phosphokinase] elevations and transaminase elevations,” Dr. Feagan said.
There were no cases of herpes zoster among patients who received placebo compared with five cases in the 45-mg upadacitinib group without prior biologic failure and 10 cases in the prior biologic failure group.
“The zoster signal is there even at induction with the 45-mg dose versus placebo,” Dr. Feagan said.
‘Encouraging’ results
The study indicates that upadacitinib is effective in improving endoscopic outcomes for patients with Crohn’s disease, regardless of their prior biologic treatments, Robin L. Dalal, MD, assistant professor of medicine at Vanderbilt University in Nashville, Tenn., said when asked to comment on the study.
“This is important because, as the treatment landscape for Crohn’s disease has expanded, sequencing of therapies has become more complex,” added Dr. Dalal, who was not involved in the research. “For upadacitinib in Crohn’s disease, prior biologic use may not be a factor in endoscopic response rates.”
The findings are “very encouraging for physicians and practitioners who treat IBD [inflammatory bowel disease] patients,” Maithili Chitnavis, MD, of the inflammatory bowel disease section at Atrium Health Gastroenterology in Charlotte, N.C., said when asked for comment.
“We clearly care about how patients feel overall, but endoscopic and histologic outcomes are important to investigate because we want to ensure there is internal healing to prevent a lot of the longstanding complications of Crohn’s disease, such as malignancy, strictures, fistulizing/penetrating disease, and need for surgery,” said Dr. Chitnavis, who was not involved with the study.
Upadacitinib is an oral agent, which distinguishes it from the injectable or infusion-based biologic therapies for Crohn’s disease, Dr. Chitnavis noted.
The finding that the medication works in patients with or without prior biologic failure is important, she said.
“With its anticipated ... approval for Crohn’s disease [by the Food and Drug Administration], it is expected that patients will have had to have demonstrated a lack of or loss of response to another biologic, specifically in the anti-TNF category (for example, infliximab, adalimumab, certolizumab) prior to starting upadacitinib due to concerns of potential side effects associated with the class of medications to which it belongs,” Dr. Chitnavis said. “Therefore, it makes it even more relevant to know how patients who have failed a prior biologic respond to this therapy.”
Dr. Feagan has reported serving as a consultant and speaker for AbbVie. Dr. Dalal has reported being a consultant for AbbVie in 2021. Dr. Chitnavis has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The findings of this subanalysis come from two phase 3 induction trials (U-EXCEL and U-EXCEED) and one maintenance study (U-ENDURE) of upadacitinib in this patient population.
“Upadacitinib shows large differences relative to placebo in endoscopic response and remission ... in a difficult-to-treat population of patients, the majority of whom had failed an advanced therapy,” lead investigator Brian Feagan, MD, senior scientific director of the GI contract research firm Alimentiv in London, Ontario, said in an interview.
“The absolute magnitude of the finding was unanticipated – a greater treatment effect than might be anticipated for these outcomes compared with other advanced treatments for Crohn’s disease in these higher-risk patients,” he said.
Dr. Feagan presented the research at the annual congress of the European Crohn’s and Colitis Organisation.
Research methodology
At baseline, participants had an average daily stool frequency of 4 or more and/or an abdominal pain score of 2 or greater. They also had a Simple Endoscopic Score for Crohn’s disease of 6 or more, excluding a narrowing component, or a score of 4 or more for isolated ileal Crohn’s disease.
In the treatment induction phase, patients were randomly assigned 2:1, with 674 people receiving 45 mg upadacitinib and 347 taking a placebo once daily for 12 weeks.
Participants who experienced at least a 30% decrease in stool frequency and/or daily abdominal pain scores were enrolled in the maintenance phase of the study. For this phase, patients were randomly assigned again, with 168 receiving 30 mg upadacitinib, 169 receiving 15 mg upadacitinib, and 165 taking a placebo once daily for 52 weeks.
In each induction and maintenance cohort, more than 70% of patients had failed one prior biologic therapy, with failure defined as inadequate response or intolerance. Among those who failed a previous biologic in induction, 96% had also failed prior treatment with an anti–tumor necrosis factor (anti-TNF) inhibitor.
Participants’ mean age was 38-40 years, and 52%-55% were men. Patients who had not failed previous therapy had Crohn’s disease for a median of 6-7 years. In contrast, the prior-failure group had Crohn’s disease for a median of 9-10 years.
Key outcomes
At 12 weeks, endoscopic response among patients who had not failed a prior biologic was 52% in the treatment group versus 16% of the placebo group. In the prior-failure group, endoscopic response was observed in 36% and 5%, respectively.
Endoscopic remission at 12 weeks among patients who had not failed a prior biologic was 36% in the treatment group versus 10% in the placebo group. In the prior-failure group, endoscopic remission was 20% in the treatment group versus 3% in those who took placebo.
Participants in the treatment groups of the 52-week maintenance phase of the study experienced higher endoscopic response and endoscopic remission rates compared with those who received placebo.
Endoscopic response in the group without prior biologic failure was 44% in the 30-mg upadacitinib group, 40% in the 15-mg group, and 18% in the placebo group. Among those with prior biologic failure, endoscopic response was seen in 39% of the 30-mg upadacitinib group, 23% of the 15-mg group, and 4% of the placebo group.
There is a “very striking difference in endoscopic response rates between the high dose and placebo,” Dr. Feagan said. “That difference here is in the response rate. You see dose separation.”
Endoscopic remission among those without prior biologic failure was observed in 34% of the 30-mg upadacitinib group, 27% of the 15-mg group, and 16% of the placebo group. Among those with prior biologic failure, endoscopic remission was seen in 27% of the 30-mg upadacitinib group, 16% of the 15-mg group, and 2% of the placebo group.
The results show “a clear advantage for the 30-mg dose versus the 15-mg in the maintenance component, especially in patients who had failed an advanced therapy,” Dr. Feagan said.
Safety signals
Upadacitinib was well tolerated in the induction and maintenance phases, and no new safety risks were observed compared with the known safety profile of the drug, the researchers noted.
For example, during the induction studies, the rate of any adverse event among patients without prior biologic failure was 60% in the 45-mg upadacitinib group and 53% in the placebo group. Among those who failed a prior biologic, the rates were 67% in the 45-mg upadacitinib group and 66% in the placebo group.
The adverse events were “issues that have already been identified with JAK inhibitors, the biochemical abnormalities with CPK [creatine phosphokinase] elevations and transaminase elevations,” Dr. Feagan said.
There were no cases of herpes zoster among patients who received placebo compared with five cases in the 45-mg upadacitinib group without prior biologic failure and 10 cases in the prior biologic failure group.
“The zoster signal is there even at induction with the 45-mg dose versus placebo,” Dr. Feagan said.
‘Encouraging’ results
The study indicates that upadacitinib is effective in improving endoscopic outcomes for patients with Crohn’s disease, regardless of their prior biologic treatments, Robin L. Dalal, MD, assistant professor of medicine at Vanderbilt University in Nashville, Tenn., said when asked to comment on the study.
“This is important because, as the treatment landscape for Crohn’s disease has expanded, sequencing of therapies has become more complex,” added Dr. Dalal, who was not involved in the research. “For upadacitinib in Crohn’s disease, prior biologic use may not be a factor in endoscopic response rates.”
The findings are “very encouraging for physicians and practitioners who treat IBD [inflammatory bowel disease] patients,” Maithili Chitnavis, MD, of the inflammatory bowel disease section at Atrium Health Gastroenterology in Charlotte, N.C., said when asked for comment.
“We clearly care about how patients feel overall, but endoscopic and histologic outcomes are important to investigate because we want to ensure there is internal healing to prevent a lot of the longstanding complications of Crohn’s disease, such as malignancy, strictures, fistulizing/penetrating disease, and need for surgery,” said Dr. Chitnavis, who was not involved with the study.
Upadacitinib is an oral agent, which distinguishes it from the injectable or infusion-based biologic therapies for Crohn’s disease, Dr. Chitnavis noted.
The finding that the medication works in patients with or without prior biologic failure is important, she said.
“With its anticipated ... approval for Crohn’s disease [by the Food and Drug Administration], it is expected that patients will have had to have demonstrated a lack of or loss of response to another biologic, specifically in the anti-TNF category (for example, infliximab, adalimumab, certolizumab) prior to starting upadacitinib due to concerns of potential side effects associated with the class of medications to which it belongs,” Dr. Chitnavis said. “Therefore, it makes it even more relevant to know how patients who have failed a prior biologic respond to this therapy.”
Dr. Feagan has reported serving as a consultant and speaker for AbbVie. Dr. Dalal has reported being a consultant for AbbVie in 2021. Dr. Chitnavis has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The findings of this subanalysis come from two phase 3 induction trials (U-EXCEL and U-EXCEED) and one maintenance study (U-ENDURE) of upadacitinib in this patient population.
“Upadacitinib shows large differences relative to placebo in endoscopic response and remission ... in a difficult-to-treat population of patients, the majority of whom had failed an advanced therapy,” lead investigator Brian Feagan, MD, senior scientific director of the GI contract research firm Alimentiv in London, Ontario, said in an interview.
“The absolute magnitude of the finding was unanticipated – a greater treatment effect than might be anticipated for these outcomes compared with other advanced treatments for Crohn’s disease in these higher-risk patients,” he said.
Dr. Feagan presented the research at the annual congress of the European Crohn’s and Colitis Organisation.
Research methodology
At baseline, participants had an average daily stool frequency of 4 or more and/or an abdominal pain score of 2 or greater. They also had a Simple Endoscopic Score for Crohn’s disease of 6 or more, excluding a narrowing component, or a score of 4 or more for isolated ileal Crohn’s disease.
In the treatment induction phase, patients were randomly assigned 2:1, with 674 people receiving 45 mg upadacitinib and 347 taking a placebo once daily for 12 weeks.
Participants who experienced at least a 30% decrease in stool frequency and/or daily abdominal pain scores were enrolled in the maintenance phase of the study. For this phase, patients were randomly assigned again, with 168 receiving 30 mg upadacitinib, 169 receiving 15 mg upadacitinib, and 165 taking a placebo once daily for 52 weeks.
In each induction and maintenance cohort, more than 70% of patients had failed one prior biologic therapy, with failure defined as inadequate response or intolerance. Among those who failed a previous biologic in induction, 96% had also failed prior treatment with an anti–tumor necrosis factor (anti-TNF) inhibitor.
Participants’ mean age was 38-40 years, and 52%-55% were men. Patients who had not failed previous therapy had Crohn’s disease for a median of 6-7 years. In contrast, the prior-failure group had Crohn’s disease for a median of 9-10 years.
Key outcomes
At 12 weeks, endoscopic response among patients who had not failed a prior biologic was 52% in the treatment group versus 16% of the placebo group. In the prior-failure group, endoscopic response was observed in 36% and 5%, respectively.
Endoscopic remission at 12 weeks among patients who had not failed a prior biologic was 36% in the treatment group versus 10% in the placebo group. In the prior-failure group, endoscopic remission was 20% in the treatment group versus 3% in those who took placebo.
Participants in the treatment groups of the 52-week maintenance phase of the study experienced higher endoscopic response and endoscopic remission rates compared with those who received placebo.
Endoscopic response in the group without prior biologic failure was 44% in the 30-mg upadacitinib group, 40% in the 15-mg group, and 18% in the placebo group. Among those with prior biologic failure, endoscopic response was seen in 39% of the 30-mg upadacitinib group, 23% of the 15-mg group, and 4% of the placebo group.
There is a “very striking difference in endoscopic response rates between the high dose and placebo,” Dr. Feagan said. “That difference here is in the response rate. You see dose separation.”
Endoscopic remission among those without prior biologic failure was observed in 34% of the 30-mg upadacitinib group, 27% of the 15-mg group, and 16% of the placebo group. Among those with prior biologic failure, endoscopic remission was seen in 27% of the 30-mg upadacitinib group, 16% of the 15-mg group, and 2% of the placebo group.
The results show “a clear advantage for the 30-mg dose versus the 15-mg in the maintenance component, especially in patients who had failed an advanced therapy,” Dr. Feagan said.
Safety signals
Upadacitinib was well tolerated in the induction and maintenance phases, and no new safety risks were observed compared with the known safety profile of the drug, the researchers noted.
For example, during the induction studies, the rate of any adverse event among patients without prior biologic failure was 60% in the 45-mg upadacitinib group and 53% in the placebo group. Among those who failed a prior biologic, the rates were 67% in the 45-mg upadacitinib group and 66% in the placebo group.
The adverse events were “issues that have already been identified with JAK inhibitors, the biochemical abnormalities with CPK [creatine phosphokinase] elevations and transaminase elevations,” Dr. Feagan said.
There were no cases of herpes zoster among patients who received placebo compared with five cases in the 45-mg upadacitinib group without prior biologic failure and 10 cases in the prior biologic failure group.
“The zoster signal is there even at induction with the 45-mg dose versus placebo,” Dr. Feagan said.
‘Encouraging’ results
The study indicates that upadacitinib is effective in improving endoscopic outcomes for patients with Crohn’s disease, regardless of their prior biologic treatments, Robin L. Dalal, MD, assistant professor of medicine at Vanderbilt University in Nashville, Tenn., said when asked to comment on the study.
“This is important because, as the treatment landscape for Crohn’s disease has expanded, sequencing of therapies has become more complex,” added Dr. Dalal, who was not involved in the research. “For upadacitinib in Crohn’s disease, prior biologic use may not be a factor in endoscopic response rates.”
The findings are “very encouraging for physicians and practitioners who treat IBD [inflammatory bowel disease] patients,” Maithili Chitnavis, MD, of the inflammatory bowel disease section at Atrium Health Gastroenterology in Charlotte, N.C., said when asked for comment.
“We clearly care about how patients feel overall, but endoscopic and histologic outcomes are important to investigate because we want to ensure there is internal healing to prevent a lot of the longstanding complications of Crohn’s disease, such as malignancy, strictures, fistulizing/penetrating disease, and need for surgery,” said Dr. Chitnavis, who was not involved with the study.
Upadacitinib is an oral agent, which distinguishes it from the injectable or infusion-based biologic therapies for Crohn’s disease, Dr. Chitnavis noted.
The finding that the medication works in patients with or without prior biologic failure is important, she said.
“With its anticipated ... approval for Crohn’s disease [by the Food and Drug Administration], it is expected that patients will have had to have demonstrated a lack of or loss of response to another biologic, specifically in the anti-TNF category (for example, infliximab, adalimumab, certolizumab) prior to starting upadacitinib due to concerns of potential side effects associated with the class of medications to which it belongs,” Dr. Chitnavis said. “Therefore, it makes it even more relevant to know how patients who have failed a prior biologic respond to this therapy.”
Dr. Feagan has reported serving as a consultant and speaker for AbbVie. Dr. Dalal has reported being a consultant for AbbVie in 2021. Dr. Chitnavis has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM ECCO 2023
Nearly one in three patients with IBD affected by skin lesions
People with inflammatory bowel disease (IBD) commonly develop skin lesions linked to their condition, but until now few researchers looked at how common they are.
, according to the prospective, single-center study.
“Skin lesions in IBD patients are much more prevalent than it is generally accepted. The lesions may be related to the pathogenesis of IBD, but it is very important to know that the modern biological therapies may also cause skin lesions,” said senior study author Laimas Jonaitis, MD, PhD, professor in the department of gastroenterology at Lithuanian University of Health Sciences in Kaunas.
“If the gastroenterologist is experienced and has enough competence, he or she may establish the diagnosis, but in all other cases it is wise and advisable to refer the patient to the dermatologist,” Dr. Jonaitis said. A referral should include the history and full treatment for IBD.
The results were presented as a poster at the annual congress of the European Crohn’s and Colitis Organisation, held in Copenhagen and virtually.
Dr. Jonaitis and colleagues conducted a literature analysis to determine the prevalence of extra-abdominal manifestations of IBD. The lack of published data prompted them to survey 152 consecutive patients with IBD receiving outpatient treatment at their institution. The patients completed questionnaires from January to October 2022 about any cutaneous lesions.
The mean age of patients was 42 years, and 58% were men. A majority, 72%, had ulcerative colitis, and 28% had Crohn’s disease.
Prevalence of skin lesions
A total of 43% of participants reported skin lesions, but only 30% of patients had lesions considered related to IBD or IBD therapy due to their emergence after the patient’s IBD diagnosis.
By IBD diagnosis, 29% of patients with ulcerative colitis and 33% of patients with Crohn’s disease had lesions related to their condition. The difference in skin lesion prevalence between the two groups was not significant (P > .05), the researchers noted.
The team further investigated the types of skin lesions deemed to be associated with IBD or IBD therapy.
Overall, they found psoriasis in nine patients, eczema in nine, erythema nodosum in six, pyoderma gangrenosum in five, allergic rash in four, and vitiligo in two. They found acne, epidermolysis bullosa acquisita, and hemorrhagic vasculitis in one patient each.
Specifically, among patients with ulcerative colitis, skin lesions were reported in 8 of 27 with left-sided colitis, 2 of 15 with ulcerative colitis proctitis, and 22 of 67 patients with pancolitis. The difference between the groups of proctitis and pancolitis was significant (P = .03).
Within the group with Crohn’s disease, skin lesions were reported in 3 of 15 patients with ileitis, 4 of 10 with colitis, and 7 of 17 with ileocolitis. The difference among these groups was not significant (P > .05).
The most common skin lesions observed in Crohn’s disease were erythema nodosum and eczema, and in ulcerative colitis, psoriasis and eczema, the researchers reported.
They also noted that the cutaneous lesions were significantly more prevalent in extensive ulcerative colitis compared with distal disease.
Skin lesions add to patient misery
“Skin lesions are considered a burden to patients with IBD and add to their suffering,” said Sara Mesilhy, MBBS, a gastroenterologist with the Royal College of Physicians in the United Kingdom, who was not affiliated with the research.
The severity and location of the disease appears to play a role because researchers found extensive ulcerative colitis may carry a higher risk for the development of skin lesions, Dr. Mesilhy noted.
The first step when facing skin lesions is to control the disease activity via the best treatment option, Dr. Mesilhy suggested.
The study was independently supported. Dr. Jonaitis and Dr. Mesilhy have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
People with inflammatory bowel disease (IBD) commonly develop skin lesions linked to their condition, but until now few researchers looked at how common they are.
, according to the prospective, single-center study.
“Skin lesions in IBD patients are much more prevalent than it is generally accepted. The lesions may be related to the pathogenesis of IBD, but it is very important to know that the modern biological therapies may also cause skin lesions,” said senior study author Laimas Jonaitis, MD, PhD, professor in the department of gastroenterology at Lithuanian University of Health Sciences in Kaunas.
“If the gastroenterologist is experienced and has enough competence, he or she may establish the diagnosis, but in all other cases it is wise and advisable to refer the patient to the dermatologist,” Dr. Jonaitis said. A referral should include the history and full treatment for IBD.
The results were presented as a poster at the annual congress of the European Crohn’s and Colitis Organisation, held in Copenhagen and virtually.
Dr. Jonaitis and colleagues conducted a literature analysis to determine the prevalence of extra-abdominal manifestations of IBD. The lack of published data prompted them to survey 152 consecutive patients with IBD receiving outpatient treatment at their institution. The patients completed questionnaires from January to October 2022 about any cutaneous lesions.
The mean age of patients was 42 years, and 58% were men. A majority, 72%, had ulcerative colitis, and 28% had Crohn’s disease.
Prevalence of skin lesions
A total of 43% of participants reported skin lesions, but only 30% of patients had lesions considered related to IBD or IBD therapy due to their emergence after the patient’s IBD diagnosis.
By IBD diagnosis, 29% of patients with ulcerative colitis and 33% of patients with Crohn’s disease had lesions related to their condition. The difference in skin lesion prevalence between the two groups was not significant (P > .05), the researchers noted.
The team further investigated the types of skin lesions deemed to be associated with IBD or IBD therapy.
Overall, they found psoriasis in nine patients, eczema in nine, erythema nodosum in six, pyoderma gangrenosum in five, allergic rash in four, and vitiligo in two. They found acne, epidermolysis bullosa acquisita, and hemorrhagic vasculitis in one patient each.
Specifically, among patients with ulcerative colitis, skin lesions were reported in 8 of 27 with left-sided colitis, 2 of 15 with ulcerative colitis proctitis, and 22 of 67 patients with pancolitis. The difference between the groups of proctitis and pancolitis was significant (P = .03).
Within the group with Crohn’s disease, skin lesions were reported in 3 of 15 patients with ileitis, 4 of 10 with colitis, and 7 of 17 with ileocolitis. The difference among these groups was not significant (P > .05).
The most common skin lesions observed in Crohn’s disease were erythema nodosum and eczema, and in ulcerative colitis, psoriasis and eczema, the researchers reported.
They also noted that the cutaneous lesions were significantly more prevalent in extensive ulcerative colitis compared with distal disease.
Skin lesions add to patient misery
“Skin lesions are considered a burden to patients with IBD and add to their suffering,” said Sara Mesilhy, MBBS, a gastroenterologist with the Royal College of Physicians in the United Kingdom, who was not affiliated with the research.
The severity and location of the disease appears to play a role because researchers found extensive ulcerative colitis may carry a higher risk for the development of skin lesions, Dr. Mesilhy noted.
The first step when facing skin lesions is to control the disease activity via the best treatment option, Dr. Mesilhy suggested.
The study was independently supported. Dr. Jonaitis and Dr. Mesilhy have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
People with inflammatory bowel disease (IBD) commonly develop skin lesions linked to their condition, but until now few researchers looked at how common they are.
, according to the prospective, single-center study.
“Skin lesions in IBD patients are much more prevalent than it is generally accepted. The lesions may be related to the pathogenesis of IBD, but it is very important to know that the modern biological therapies may also cause skin lesions,” said senior study author Laimas Jonaitis, MD, PhD, professor in the department of gastroenterology at Lithuanian University of Health Sciences in Kaunas.
“If the gastroenterologist is experienced and has enough competence, he or she may establish the diagnosis, but in all other cases it is wise and advisable to refer the patient to the dermatologist,” Dr. Jonaitis said. A referral should include the history and full treatment for IBD.
The results were presented as a poster at the annual congress of the European Crohn’s and Colitis Organisation, held in Copenhagen and virtually.
Dr. Jonaitis and colleagues conducted a literature analysis to determine the prevalence of extra-abdominal manifestations of IBD. The lack of published data prompted them to survey 152 consecutive patients with IBD receiving outpatient treatment at their institution. The patients completed questionnaires from January to October 2022 about any cutaneous lesions.
The mean age of patients was 42 years, and 58% were men. A majority, 72%, had ulcerative colitis, and 28% had Crohn’s disease.
Prevalence of skin lesions
A total of 43% of participants reported skin lesions, but only 30% of patients had lesions considered related to IBD or IBD therapy due to their emergence after the patient’s IBD diagnosis.
By IBD diagnosis, 29% of patients with ulcerative colitis and 33% of patients with Crohn’s disease had lesions related to their condition. The difference in skin lesion prevalence between the two groups was not significant (P > .05), the researchers noted.
The team further investigated the types of skin lesions deemed to be associated with IBD or IBD therapy.
Overall, they found psoriasis in nine patients, eczema in nine, erythema nodosum in six, pyoderma gangrenosum in five, allergic rash in four, and vitiligo in two. They found acne, epidermolysis bullosa acquisita, and hemorrhagic vasculitis in one patient each.
Specifically, among patients with ulcerative colitis, skin lesions were reported in 8 of 27 with left-sided colitis, 2 of 15 with ulcerative colitis proctitis, and 22 of 67 patients with pancolitis. The difference between the groups of proctitis and pancolitis was significant (P = .03).
Within the group with Crohn’s disease, skin lesions were reported in 3 of 15 patients with ileitis, 4 of 10 with colitis, and 7 of 17 with ileocolitis. The difference among these groups was not significant (P > .05).
The most common skin lesions observed in Crohn’s disease were erythema nodosum and eczema, and in ulcerative colitis, psoriasis and eczema, the researchers reported.
They also noted that the cutaneous lesions were significantly more prevalent in extensive ulcerative colitis compared with distal disease.
Skin lesions add to patient misery
“Skin lesions are considered a burden to patients with IBD and add to their suffering,” said Sara Mesilhy, MBBS, a gastroenterologist with the Royal College of Physicians in the United Kingdom, who was not affiliated with the research.
The severity and location of the disease appears to play a role because researchers found extensive ulcerative colitis may carry a higher risk for the development of skin lesions, Dr. Mesilhy noted.
The first step when facing skin lesions is to control the disease activity via the best treatment option, Dr. Mesilhy suggested.
The study was independently supported. Dr. Jonaitis and Dr. Mesilhy have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM ECCO 2023
AI-assisted colonoscopy in IBD: Not all it’s cut out to be?
Within the rising tide of studies extolling the benefits of artificial intelligence for improving adenoma detection during colonoscopy comes new research suggesting the contrary, at least among people with inflammatory bowel disease (IBD).
Researchers retrospectively studied almost 1,000 colonoscopies before and after introduction of an AI system (GI Genius, Medtronic) at a tertiary medical center in Israel in which a large volume of endoscopies was performed. , and it was significantly higher for colonoscopies performed by gastroenterologists who had 5 or more years of experience, compared with the ADR for AI-assisted colonoscopies.
The lower ADR rate in AI-assisted procedures could be the result of an overreliance on the AI technology and shorter procedure times, which may have led to an underrecognition of adenomas, lead investigator Asaf Levartovsky, MD, said in an interview.
“AI is an aid to the endoscopist, not a replacement to the endoscopist,” added Dr. Levartovsky, a gastroenterologist at Sheba Medical Center, Tel Aviv.
The results were presented as a poster at the annual congress of the European Crohn’s and Colitis Organisation, held in Copenhagen and virtually.
Key findings
The use of AI has recently been shown to improve colorectal cancer screening overall, the authors note. ADR is a measure of the quality of screening colonoscopies. Detection rates were at least 20% among women and 30% among men, “indicative of adequate performance.”
The ADR for people with IBD can be lower than it is for average-risk patients, however, owing to a difference in age in the two populations and the presence of dysplasia-associated lesions, as opposed to sporadic adenomas, for patients with IBD, the researchers note. There is no consensus on an acceptable ADR target for patients with IBD, and the impact of AI-assisted colonoscopy in this patient population hasn’t been explored, they add.
To learn more, Dr. Levartovsky and colleagues compared 237 screening colonoscopies conducted in the 11 months before AI was introduced at the medical center in July 2021 to 759 colonoscopies performed in the 15 months after its introduction.
The pre-AI patient group and the AI patient group were similar (mean age, 44-45 years; about 55% men in each group). Crohn’s disease was more common than ulcerative colitis (63% in the pre-AI cohort and 57% in the AI-assisted cohort).
The ADR in the pre-AI group was 6.3%, compared with 4% in the AI-assisted group (P = .15). The distinction became significant, at 7.6% versus 3.8% (P = .035), when researchers evaluated colonoscopies performed by gastroenterologists who had 5 or more years of experience.
Total procedure time was longer for the patients in the pre-AI group, at 25 minutes, compared with 21 minutes in the AI-assisted group. This difference was statistically significant (P < .0001).
“I think this poster raises questions regarding the real-world utility of AI for adenoma detection [in patients with IBD],” Dr. Levartovsky said.
Dr. Levartovsky said he was not surprised by their findings, because they are similar to those reported in a recent article from his group, although this earlier study did not focus on patients with IBD.
The research had some limitations. The study was not case-control matched, and the pre-AI group was considerably smaller than the AI group.
Study design a factor
The study design could account for the difference in its findings, compared with research indicating that AI-assisted colonoscopies improve ADR, Cesare Hassan, MD, associate professor of gastroenterology at Humanitas University, Milan, said in an interview.
The study was retrospective, so researchers could not randomly assign people to the AI or the no-AI group. It therefore was not possible to ensure that the prevalence of disease was equivalent between the two groups, he said.
By comparison, the previous studies showing the benefits of AI-assisted colonoscopy with regard to ADR were randomized, controlled clinical trials, Dr. Hassan said.
The study was independently supported. Dr. Levartovsky and Dr. Hassan report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Within the rising tide of studies extolling the benefits of artificial intelligence for improving adenoma detection during colonoscopy comes new research suggesting the contrary, at least among people with inflammatory bowel disease (IBD).
Researchers retrospectively studied almost 1,000 colonoscopies before and after introduction of an AI system (GI Genius, Medtronic) at a tertiary medical center in Israel in which a large volume of endoscopies was performed. , and it was significantly higher for colonoscopies performed by gastroenterologists who had 5 or more years of experience, compared with the ADR for AI-assisted colonoscopies.
The lower ADR rate in AI-assisted procedures could be the result of an overreliance on the AI technology and shorter procedure times, which may have led to an underrecognition of adenomas, lead investigator Asaf Levartovsky, MD, said in an interview.
“AI is an aid to the endoscopist, not a replacement to the endoscopist,” added Dr. Levartovsky, a gastroenterologist at Sheba Medical Center, Tel Aviv.
The results were presented as a poster at the annual congress of the European Crohn’s and Colitis Organisation, held in Copenhagen and virtually.
Key findings
The use of AI has recently been shown to improve colorectal cancer screening overall, the authors note. ADR is a measure of the quality of screening colonoscopies. Detection rates were at least 20% among women and 30% among men, “indicative of adequate performance.”
The ADR for people with IBD can be lower than it is for average-risk patients, however, owing to a difference in age in the two populations and the presence of dysplasia-associated lesions, as opposed to sporadic adenomas, for patients with IBD, the researchers note. There is no consensus on an acceptable ADR target for patients with IBD, and the impact of AI-assisted colonoscopy in this patient population hasn’t been explored, they add.
To learn more, Dr. Levartovsky and colleagues compared 237 screening colonoscopies conducted in the 11 months before AI was introduced at the medical center in July 2021 to 759 colonoscopies performed in the 15 months after its introduction.
The pre-AI patient group and the AI patient group were similar (mean age, 44-45 years; about 55% men in each group). Crohn’s disease was more common than ulcerative colitis (63% in the pre-AI cohort and 57% in the AI-assisted cohort).
The ADR in the pre-AI group was 6.3%, compared with 4% in the AI-assisted group (P = .15). The distinction became significant, at 7.6% versus 3.8% (P = .035), when researchers evaluated colonoscopies performed by gastroenterologists who had 5 or more years of experience.
Total procedure time was longer for the patients in the pre-AI group, at 25 minutes, compared with 21 minutes in the AI-assisted group. This difference was statistically significant (P < .0001).
“I think this poster raises questions regarding the real-world utility of AI for adenoma detection [in patients with IBD],” Dr. Levartovsky said.
Dr. Levartovsky said he was not surprised by their findings, because they are similar to those reported in a recent article from his group, although this earlier study did not focus on patients with IBD.
The research had some limitations. The study was not case-control matched, and the pre-AI group was considerably smaller than the AI group.
Study design a factor
The study design could account for the difference in its findings, compared with research indicating that AI-assisted colonoscopies improve ADR, Cesare Hassan, MD, associate professor of gastroenterology at Humanitas University, Milan, said in an interview.
The study was retrospective, so researchers could not randomly assign people to the AI or the no-AI group. It therefore was not possible to ensure that the prevalence of disease was equivalent between the two groups, he said.
By comparison, the previous studies showing the benefits of AI-assisted colonoscopy with regard to ADR were randomized, controlled clinical trials, Dr. Hassan said.
The study was independently supported. Dr. Levartovsky and Dr. Hassan report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Within the rising tide of studies extolling the benefits of artificial intelligence for improving adenoma detection during colonoscopy comes new research suggesting the contrary, at least among people with inflammatory bowel disease (IBD).
Researchers retrospectively studied almost 1,000 colonoscopies before and after introduction of an AI system (GI Genius, Medtronic) at a tertiary medical center in Israel in which a large volume of endoscopies was performed. , and it was significantly higher for colonoscopies performed by gastroenterologists who had 5 or more years of experience, compared with the ADR for AI-assisted colonoscopies.
The lower ADR rate in AI-assisted procedures could be the result of an overreliance on the AI technology and shorter procedure times, which may have led to an underrecognition of adenomas, lead investigator Asaf Levartovsky, MD, said in an interview.
“AI is an aid to the endoscopist, not a replacement to the endoscopist,” added Dr. Levartovsky, a gastroenterologist at Sheba Medical Center, Tel Aviv.
The results were presented as a poster at the annual congress of the European Crohn’s and Colitis Organisation, held in Copenhagen and virtually.
Key findings
The use of AI has recently been shown to improve colorectal cancer screening overall, the authors note. ADR is a measure of the quality of screening colonoscopies. Detection rates were at least 20% among women and 30% among men, “indicative of adequate performance.”
The ADR for people with IBD can be lower than it is for average-risk patients, however, owing to a difference in age in the two populations and the presence of dysplasia-associated lesions, as opposed to sporadic adenomas, for patients with IBD, the researchers note. There is no consensus on an acceptable ADR target for patients with IBD, and the impact of AI-assisted colonoscopy in this patient population hasn’t been explored, they add.
To learn more, Dr. Levartovsky and colleagues compared 237 screening colonoscopies conducted in the 11 months before AI was introduced at the medical center in July 2021 to 759 colonoscopies performed in the 15 months after its introduction.
The pre-AI patient group and the AI patient group were similar (mean age, 44-45 years; about 55% men in each group). Crohn’s disease was more common than ulcerative colitis (63% in the pre-AI cohort and 57% in the AI-assisted cohort).
The ADR in the pre-AI group was 6.3%, compared with 4% in the AI-assisted group (P = .15). The distinction became significant, at 7.6% versus 3.8% (P = .035), when researchers evaluated colonoscopies performed by gastroenterologists who had 5 or more years of experience.
Total procedure time was longer for the patients in the pre-AI group, at 25 minutes, compared with 21 minutes in the AI-assisted group. This difference was statistically significant (P < .0001).
“I think this poster raises questions regarding the real-world utility of AI for adenoma detection [in patients with IBD],” Dr. Levartovsky said.
Dr. Levartovsky said he was not surprised by their findings, because they are similar to those reported in a recent article from his group, although this earlier study did not focus on patients with IBD.
The research had some limitations. The study was not case-control matched, and the pre-AI group was considerably smaller than the AI group.
Study design a factor
The study design could account for the difference in its findings, compared with research indicating that AI-assisted colonoscopies improve ADR, Cesare Hassan, MD, associate professor of gastroenterology at Humanitas University, Milan, said in an interview.
The study was retrospective, so researchers could not randomly assign people to the AI or the no-AI group. It therefore was not possible to ensure that the prevalence of disease was equivalent between the two groups, he said.
By comparison, the previous studies showing the benefits of AI-assisted colonoscopy with regard to ADR were randomized, controlled clinical trials, Dr. Hassan said.
The study was independently supported. Dr. Levartovsky and Dr. Hassan report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM ECCO 2023
Crohn’s disease remission rates ‘remarkably higher’ with vedolizumab
COPENHAGEN –
The study was presented at the annual congress of the European Crohn’s and Colitis Organization by Wolfgang Mohl, MD, of the Center for Gastroenterology in Saarbrucken, Germany, who suggested this biologic, which is a monoclonal antibody, could possibly be used as a first-line treatment instead of as a second or third choice. Currently, TNF inhibitors are generally prescribed first.
“Compared to previous research clinical trials, this prospective 2-year real-world study comparing vedolizumab with anti-TNF showed that, in biologic-naive Crohn’s disease patients, remission rates at 2 years with vedolizumab were remarkably higher than with anti-TNF [therapy],” Dr. Mohl and colleagues wrote in the study abstract.
“Now we know vedolizumab is a good first-line drug and that patients can stay on it for a long time,” he said in an interview. “These data also suggest that we are wrong in thinking TNF inhibitors should be standard. I don’t think this belief holds true anymore.”
The study included 63 biologic-naive patients who were treated with vedolizumab and 197 patients who were treated with anti-TNF agents adalimumab (58.4%) and infliximab (41.6%).
After 2 years, approximately 83% of patients who were treated with vedolizumab were still receiving treatment, but only 56% of patients who received anti-TNF therapy were still undergoing therapy with either adalimumab or infliximab. After 2 years of treatment, 64.2% of patients who were treated with vedolizumab were in clinical remission, compared with 44.7% of patients who were treated with anti-TNF therapy. And, 62.5% of patients who were treated with vedolizumab were not receiving steroid treatment, compared with 41.6% of patients in the anti-TNF therapy group. This, Dr. Mohl said, was a statistically significant difference (P < .05).
“It is clinically relevant to achieve remission without steroids because this is hard to obtain,” he said. “Patients really don’t want to have to take steroids because they can experience lots of side effects including osteoporosis. It’s good to be in remission, but to be in steroid-free remission is so much better.”
Vedolizumab is a relatively new drug, compared with infliximab and adalimumab, which were approved by the Food and Drug Administration in 1998 and 2008, respectively. “We wanted real-world data to help us understand the pattern of outcomes outside of the clinical trial environment,” Dr. Mohl said.
From 45 treatment centers across Germany, researchers prospectively enrolled 1,200 biologic-naive and biologic-experienced patients with either Crohn’s disease or ulcerative colitis between 2017 and 2020 into the VEDOIBD study. This analysis was limited to 260 patients with Crohn’s disease.
In addition to a higher proportion of patients on vedolizumab continuing on treatment, compared with patients on anti–TNF inhibitor therapy, there was a significantly higher clinical remission rate with vedolizumab (64.2%), compared with anti-TNFi therapy (44.7%) after 2 years (P < .05). Researchers used a statistical method to determine the effect of 2-year maintenance in only those patients who responded to a 3-month induction, and they found a significantly better response in terms of clinical remission in patients on vedolizumab (88.6%), compared with anti-TNF inhibitors (45.8%) (P = .0001), and likewise in steroid-free remission with 86.8% for vedolizumab, compared with 44.1% for anti-TNF inhibitors (P < .001).
Dr. Mohl described his experience with vedolizumab in clinical practice. “Vedolizumab may take a little longer to work but then we don’t lose patients due to side effects, which we see more often with anti-TNF therapy,” he said, adding that around 60% of patients experience side effects but around 10% actually stop anti-TNF because of side effects.
“We often lose patients because they develop antidrug antibodies, but also due to escape mechanisms, as well as dermatological side effects including psoriasis which is really annoying for patients. We also find that anti-TNF drugs just stop working after 12-18 months, and then we need to use steroids which patients dislike,” he said.
Andreas Stallmach, MD, director of gastroenterology, Friedrich Schiller University Jena (Germany), described the findings as important.
“I see this as a really important real-world data study and to summarize, vedolizumab in Crohn’s disease is better than expected. The main explanation for the difference is due to loss of response in the anti-TNF group and this could be explained by the development of autoantibodies against anti-TNF drugs. Now, vedolizumab could be a first-line treatment in patients with Crohn’s disease, especially patients with risk factors for, or history of infections, of comorbidities,” he said.
As a modern monoclonal antibody, vedolizumab uses fewer autoantibodies, compared with infliximab, which is much older, Dr. Stallmach said. “If we combine infliximab with an immunosuppressant agent, such as azathioprine, then we can prevent autoantibody development and increase the efficacy and adherence rate, but with this comes the increased risk of infections and malignancies.”
Dr. Mohl receives research support from companies involved in making biologics for inflammatory bowel disease. Dr. Stallmach is on the advisory boards of most companies that make biologics, including Takeda, which sponsored this study.
* This article was updated March 10, 2023.
COPENHAGEN –
The study was presented at the annual congress of the European Crohn’s and Colitis Organization by Wolfgang Mohl, MD, of the Center for Gastroenterology in Saarbrucken, Germany, who suggested this biologic, which is a monoclonal antibody, could possibly be used as a first-line treatment instead of as a second or third choice. Currently, TNF inhibitors are generally prescribed first.
“Compared to previous research clinical trials, this prospective 2-year real-world study comparing vedolizumab with anti-TNF showed that, in biologic-naive Crohn’s disease patients, remission rates at 2 years with vedolizumab were remarkably higher than with anti-TNF [therapy],” Dr. Mohl and colleagues wrote in the study abstract.
“Now we know vedolizumab is a good first-line drug and that patients can stay on it for a long time,” he said in an interview. “These data also suggest that we are wrong in thinking TNF inhibitors should be standard. I don’t think this belief holds true anymore.”
The study included 63 biologic-naive patients who were treated with vedolizumab and 197 patients who were treated with anti-TNF agents adalimumab (58.4%) and infliximab (41.6%).
After 2 years, approximately 83% of patients who were treated with vedolizumab were still receiving treatment, but only 56% of patients who received anti-TNF therapy were still undergoing therapy with either adalimumab or infliximab. After 2 years of treatment, 64.2% of patients who were treated with vedolizumab were in clinical remission, compared with 44.7% of patients who were treated with anti-TNF therapy. And, 62.5% of patients who were treated with vedolizumab were not receiving steroid treatment, compared with 41.6% of patients in the anti-TNF therapy group. This, Dr. Mohl said, was a statistically significant difference (P < .05).
“It is clinically relevant to achieve remission without steroids because this is hard to obtain,” he said. “Patients really don’t want to have to take steroids because they can experience lots of side effects including osteoporosis. It’s good to be in remission, but to be in steroid-free remission is so much better.”
Vedolizumab is a relatively new drug, compared with infliximab and adalimumab, which were approved by the Food and Drug Administration in 1998 and 2008, respectively. “We wanted real-world data to help us understand the pattern of outcomes outside of the clinical trial environment,” Dr. Mohl said.
From 45 treatment centers across Germany, researchers prospectively enrolled 1,200 biologic-naive and biologic-experienced patients with either Crohn’s disease or ulcerative colitis between 2017 and 2020 into the VEDOIBD study. This analysis was limited to 260 patients with Crohn’s disease.
In addition to a higher proportion of patients on vedolizumab continuing on treatment, compared with patients on anti–TNF inhibitor therapy, there was a significantly higher clinical remission rate with vedolizumab (64.2%), compared with anti-TNFi therapy (44.7%) after 2 years (P < .05). Researchers used a statistical method to determine the effect of 2-year maintenance in only those patients who responded to a 3-month induction, and they found a significantly better response in terms of clinical remission in patients on vedolizumab (88.6%), compared with anti-TNF inhibitors (45.8%) (P = .0001), and likewise in steroid-free remission with 86.8% for vedolizumab, compared with 44.1% for anti-TNF inhibitors (P < .001).
Dr. Mohl described his experience with vedolizumab in clinical practice. “Vedolizumab may take a little longer to work but then we don’t lose patients due to side effects, which we see more often with anti-TNF therapy,” he said, adding that around 60% of patients experience side effects but around 10% actually stop anti-TNF because of side effects.
“We often lose patients because they develop antidrug antibodies, but also due to escape mechanisms, as well as dermatological side effects including psoriasis which is really annoying for patients. We also find that anti-TNF drugs just stop working after 12-18 months, and then we need to use steroids which patients dislike,” he said.
Andreas Stallmach, MD, director of gastroenterology, Friedrich Schiller University Jena (Germany), described the findings as important.
“I see this as a really important real-world data study and to summarize, vedolizumab in Crohn’s disease is better than expected. The main explanation for the difference is due to loss of response in the anti-TNF group and this could be explained by the development of autoantibodies against anti-TNF drugs. Now, vedolizumab could be a first-line treatment in patients with Crohn’s disease, especially patients with risk factors for, or history of infections, of comorbidities,” he said.
As a modern monoclonal antibody, vedolizumab uses fewer autoantibodies, compared with infliximab, which is much older, Dr. Stallmach said. “If we combine infliximab with an immunosuppressant agent, such as azathioprine, then we can prevent autoantibody development and increase the efficacy and adherence rate, but with this comes the increased risk of infections and malignancies.”
Dr. Mohl receives research support from companies involved in making biologics for inflammatory bowel disease. Dr. Stallmach is on the advisory boards of most companies that make biologics, including Takeda, which sponsored this study.
* This article was updated March 10, 2023.
COPENHAGEN –
The study was presented at the annual congress of the European Crohn’s and Colitis Organization by Wolfgang Mohl, MD, of the Center for Gastroenterology in Saarbrucken, Germany, who suggested this biologic, which is a monoclonal antibody, could possibly be used as a first-line treatment instead of as a second or third choice. Currently, TNF inhibitors are generally prescribed first.
“Compared to previous research clinical trials, this prospective 2-year real-world study comparing vedolizumab with anti-TNF showed that, in biologic-naive Crohn’s disease patients, remission rates at 2 years with vedolizumab were remarkably higher than with anti-TNF [therapy],” Dr. Mohl and colleagues wrote in the study abstract.
“Now we know vedolizumab is a good first-line drug and that patients can stay on it for a long time,” he said in an interview. “These data also suggest that we are wrong in thinking TNF inhibitors should be standard. I don’t think this belief holds true anymore.”
The study included 63 biologic-naive patients who were treated with vedolizumab and 197 patients who were treated with anti-TNF agents adalimumab (58.4%) and infliximab (41.6%).
After 2 years, approximately 83% of patients who were treated with vedolizumab were still receiving treatment, but only 56% of patients who received anti-TNF therapy were still undergoing therapy with either adalimumab or infliximab. After 2 years of treatment, 64.2% of patients who were treated with vedolizumab were in clinical remission, compared with 44.7% of patients who were treated with anti-TNF therapy. And, 62.5% of patients who were treated with vedolizumab were not receiving steroid treatment, compared with 41.6% of patients in the anti-TNF therapy group. This, Dr. Mohl said, was a statistically significant difference (P < .05).
“It is clinically relevant to achieve remission without steroids because this is hard to obtain,” he said. “Patients really don’t want to have to take steroids because they can experience lots of side effects including osteoporosis. It’s good to be in remission, but to be in steroid-free remission is so much better.”
Vedolizumab is a relatively new drug, compared with infliximab and adalimumab, which were approved by the Food and Drug Administration in 1998 and 2008, respectively. “We wanted real-world data to help us understand the pattern of outcomes outside of the clinical trial environment,” Dr. Mohl said.
From 45 treatment centers across Germany, researchers prospectively enrolled 1,200 biologic-naive and biologic-experienced patients with either Crohn’s disease or ulcerative colitis between 2017 and 2020 into the VEDOIBD study. This analysis was limited to 260 patients with Crohn’s disease.
In addition to a higher proportion of patients on vedolizumab continuing on treatment, compared with patients on anti–TNF inhibitor therapy, there was a significantly higher clinical remission rate with vedolizumab (64.2%), compared with anti-TNFi therapy (44.7%) after 2 years (P < .05). Researchers used a statistical method to determine the effect of 2-year maintenance in only those patients who responded to a 3-month induction, and they found a significantly better response in terms of clinical remission in patients on vedolizumab (88.6%), compared with anti-TNF inhibitors (45.8%) (P = .0001), and likewise in steroid-free remission with 86.8% for vedolizumab, compared with 44.1% for anti-TNF inhibitors (P < .001).
Dr. Mohl described his experience with vedolizumab in clinical practice. “Vedolizumab may take a little longer to work but then we don’t lose patients due to side effects, which we see more often with anti-TNF therapy,” he said, adding that around 60% of patients experience side effects but around 10% actually stop anti-TNF because of side effects.
“We often lose patients because they develop antidrug antibodies, but also due to escape mechanisms, as well as dermatological side effects including psoriasis which is really annoying for patients. We also find that anti-TNF drugs just stop working after 12-18 months, and then we need to use steroids which patients dislike,” he said.
Andreas Stallmach, MD, director of gastroenterology, Friedrich Schiller University Jena (Germany), described the findings as important.
“I see this as a really important real-world data study and to summarize, vedolizumab in Crohn’s disease is better than expected. The main explanation for the difference is due to loss of response in the anti-TNF group and this could be explained by the development of autoantibodies against anti-TNF drugs. Now, vedolizumab could be a first-line treatment in patients with Crohn’s disease, especially patients with risk factors for, or history of infections, of comorbidities,” he said.
As a modern monoclonal antibody, vedolizumab uses fewer autoantibodies, compared with infliximab, which is much older, Dr. Stallmach said. “If we combine infliximab with an immunosuppressant agent, such as azathioprine, then we can prevent autoantibody development and increase the efficacy and adherence rate, but with this comes the increased risk of infections and malignancies.”
Dr. Mohl receives research support from companies involved in making biologics for inflammatory bowel disease. Dr. Stallmach is on the advisory boards of most companies that make biologics, including Takeda, which sponsored this study.
* This article was updated March 10, 2023.
AT ECCO 2023
Mental health risks higher among young people with IBD
, a new U.K. study suggests.
The retrospective, observational study of young people with IBD versus those without assessed the incidence of a wide range of mental health conditions in people aged 5-25 years.
“Anxiety and depression will not be a surprise to most of us. But we also saw changes for eating disorders, PTSD, and sleep changes,” said Richard K. Russell, MD, a pediatric gastroenterologist at the Royal Hospital for Sick Children, Edinburgh.
Dr. Russell presented the research at the annual congress of the European Crohn’s and Colitis Organisation, held in Copenhagen and virtually.
The findings indicate an unmet need for mental health care for young patients with IBD, he said. “All of us at ECCO need to address this gap.”
Key findings
Dr. Russell and colleagues identified 3,898 young people diagnosed with IBD in the 10-year period Jan. 1, 2010, through Jan. 1, 2020, using the Optimum Patient Care Research Database, which includes de-identified data from more than 1,000 general practices across the United Kingdom. They used propensity score matching to create a control group of 15,571 people without IBD, controlling for age, sex, socioeconomic status, ethnicity, and health conditions other than IBD.
Median follow-up was about 3 years.
The cumulative lifetime risk for developing any mental health condition by age 25 was 31.1% in the IBD group versus 25.1% in controls, a statistically significant difference.
Compared with the control group, the people with incident IBD were significantly more likely to develop the following:
- PTSD.
- Eating disorders.
- Self-harm.
- Sleep disturbance.
- Depression.
- Anxiety disorder.
- ‘Any mental health condition.’
Those most are risk included males overall, and specifically boys aged 12-17 years. Those with Crohn’s disease versus other types of IBD were also most at risk.
In a subgroup analysis, presented as a poster at the meeting, Dr. Russell and colleagues also found that mental health comorbidity in children and young adults with IBD is associated with increased IBD symptoms and health care utilization, as well as time off work.
Children and young adults with both IBD and mental health conditions should be monitored and receive appropriate mental health support as part of their multidisciplinary care, Dr. Russell said.
Dr. Russell added that the study period ended a few months before the COVID-19 pandemic began, so the research does not reflect its impact on mental health in the study population.
“The number of children and young adults we’re seeing in our clinic with mental health issues has rocketed through the roof because of the pandemic,” he said.
Dr. Russell suggested that the organization create a psychology subgroup called Proactive Psychologists of ECCO, or Prosecco for short.
Clinical implications
The study is important for highlighting the increased burden of mental health problems in young people with IBD, said session comoderator Nick Kennedy, MD, a consultant gastroenterologist and chief research information officer with the Royal Devon University Healthcare NHS Foundation Trust in England.
Dr. Kennedy, who was not affiliated with the research, is also supportive of the idea of a psychological subgroup within ECCO.
The peak age for developing mental health disorders found by the study (12-17 years) “is a unique and very sensitive time,” said Sara Mesilhy, MBBS, a gastroenterologist with the Royal College of Physicians in London.
“These results highlight the need for development of early screening psychiatric programs starting from time of diagnosis and continuing on periodic intervals to offer the best management plan for IBD patients, especially those with childhood-onset IBD,” said Dr. Mesilhy, who was not affiliated with the research.
Such programs would “improve the patient’s quality of life, protecting them from a lot of suffering and preventing the bad sequelae for these disorders,” said Dr. Mesilhy. “Moreover, we still need further studies to identify the most efficient monitoring and treatment protocols.”
Dr. Kennedy applauded the researchers for conducting a population-based study because it ensured an adequate cohort size and maximized identification of mental health disorders.
“It was interesting to see that there were a range of conditions where risk was increased, and that males with IBD were at particularly increased risk,” he added.
Researchers’ use of coded primary care data was a study limitation, but it was “appropriately acknowledged by the presenter,” Dr. Kennedy said.
The study was supported by Pfizer. Dr. Russell disclosed he is a consultant and member of a speakers’ bureau for Pfizer outside the submitted work. Dr. Kennedy and Dr. Mesilhy report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new U.K. study suggests.
The retrospective, observational study of young people with IBD versus those without assessed the incidence of a wide range of mental health conditions in people aged 5-25 years.
“Anxiety and depression will not be a surprise to most of us. But we also saw changes for eating disorders, PTSD, and sleep changes,” said Richard K. Russell, MD, a pediatric gastroenterologist at the Royal Hospital for Sick Children, Edinburgh.
Dr. Russell presented the research at the annual congress of the European Crohn’s and Colitis Organisation, held in Copenhagen and virtually.
The findings indicate an unmet need for mental health care for young patients with IBD, he said. “All of us at ECCO need to address this gap.”
Key findings
Dr. Russell and colleagues identified 3,898 young people diagnosed with IBD in the 10-year period Jan. 1, 2010, through Jan. 1, 2020, using the Optimum Patient Care Research Database, which includes de-identified data from more than 1,000 general practices across the United Kingdom. They used propensity score matching to create a control group of 15,571 people without IBD, controlling for age, sex, socioeconomic status, ethnicity, and health conditions other than IBD.
Median follow-up was about 3 years.
The cumulative lifetime risk for developing any mental health condition by age 25 was 31.1% in the IBD group versus 25.1% in controls, a statistically significant difference.
Compared with the control group, the people with incident IBD were significantly more likely to develop the following:
- PTSD.
- Eating disorders.
- Self-harm.
- Sleep disturbance.
- Depression.
- Anxiety disorder.
- ‘Any mental health condition.’
Those most are risk included males overall, and specifically boys aged 12-17 years. Those with Crohn’s disease versus other types of IBD were also most at risk.
In a subgroup analysis, presented as a poster at the meeting, Dr. Russell and colleagues also found that mental health comorbidity in children and young adults with IBD is associated with increased IBD symptoms and health care utilization, as well as time off work.
Children and young adults with both IBD and mental health conditions should be monitored and receive appropriate mental health support as part of their multidisciplinary care, Dr. Russell said.
Dr. Russell added that the study period ended a few months before the COVID-19 pandemic began, so the research does not reflect its impact on mental health in the study population.
“The number of children and young adults we’re seeing in our clinic with mental health issues has rocketed through the roof because of the pandemic,” he said.
Dr. Russell suggested that the organization create a psychology subgroup called Proactive Psychologists of ECCO, or Prosecco for short.
Clinical implications
The study is important for highlighting the increased burden of mental health problems in young people with IBD, said session comoderator Nick Kennedy, MD, a consultant gastroenterologist and chief research information officer with the Royal Devon University Healthcare NHS Foundation Trust in England.
Dr. Kennedy, who was not affiliated with the research, is also supportive of the idea of a psychological subgroup within ECCO.
The peak age for developing mental health disorders found by the study (12-17 years) “is a unique and very sensitive time,” said Sara Mesilhy, MBBS, a gastroenterologist with the Royal College of Physicians in London.
“These results highlight the need for development of early screening psychiatric programs starting from time of diagnosis and continuing on periodic intervals to offer the best management plan for IBD patients, especially those with childhood-onset IBD,” said Dr. Mesilhy, who was not affiliated with the research.
Such programs would “improve the patient’s quality of life, protecting them from a lot of suffering and preventing the bad sequelae for these disorders,” said Dr. Mesilhy. “Moreover, we still need further studies to identify the most efficient monitoring and treatment protocols.”
Dr. Kennedy applauded the researchers for conducting a population-based study because it ensured an adequate cohort size and maximized identification of mental health disorders.
“It was interesting to see that there were a range of conditions where risk was increased, and that males with IBD were at particularly increased risk,” he added.
Researchers’ use of coded primary care data was a study limitation, but it was “appropriately acknowledged by the presenter,” Dr. Kennedy said.
The study was supported by Pfizer. Dr. Russell disclosed he is a consultant and member of a speakers’ bureau for Pfizer outside the submitted work. Dr. Kennedy and Dr. Mesilhy report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new U.K. study suggests.
The retrospective, observational study of young people with IBD versus those without assessed the incidence of a wide range of mental health conditions in people aged 5-25 years.
“Anxiety and depression will not be a surprise to most of us. But we also saw changes for eating disorders, PTSD, and sleep changes,” said Richard K. Russell, MD, a pediatric gastroenterologist at the Royal Hospital for Sick Children, Edinburgh.
Dr. Russell presented the research at the annual congress of the European Crohn’s and Colitis Organisation, held in Copenhagen and virtually.
The findings indicate an unmet need for mental health care for young patients with IBD, he said. “All of us at ECCO need to address this gap.”
Key findings
Dr. Russell and colleagues identified 3,898 young people diagnosed with IBD in the 10-year period Jan. 1, 2010, through Jan. 1, 2020, using the Optimum Patient Care Research Database, which includes de-identified data from more than 1,000 general practices across the United Kingdom. They used propensity score matching to create a control group of 15,571 people without IBD, controlling for age, sex, socioeconomic status, ethnicity, and health conditions other than IBD.
Median follow-up was about 3 years.
The cumulative lifetime risk for developing any mental health condition by age 25 was 31.1% in the IBD group versus 25.1% in controls, a statistically significant difference.
Compared with the control group, the people with incident IBD were significantly more likely to develop the following:
- PTSD.
- Eating disorders.
- Self-harm.
- Sleep disturbance.
- Depression.
- Anxiety disorder.
- ‘Any mental health condition.’
Those most are risk included males overall, and specifically boys aged 12-17 years. Those with Crohn’s disease versus other types of IBD were also most at risk.
In a subgroup analysis, presented as a poster at the meeting, Dr. Russell and colleagues also found that mental health comorbidity in children and young adults with IBD is associated with increased IBD symptoms and health care utilization, as well as time off work.
Children and young adults with both IBD and mental health conditions should be monitored and receive appropriate mental health support as part of their multidisciplinary care, Dr. Russell said.
Dr. Russell added that the study period ended a few months before the COVID-19 pandemic began, so the research does not reflect its impact on mental health in the study population.
“The number of children and young adults we’re seeing in our clinic with mental health issues has rocketed through the roof because of the pandemic,” he said.
Dr. Russell suggested that the organization create a psychology subgroup called Proactive Psychologists of ECCO, or Prosecco for short.
Clinical implications
The study is important for highlighting the increased burden of mental health problems in young people with IBD, said session comoderator Nick Kennedy, MD, a consultant gastroenterologist and chief research information officer with the Royal Devon University Healthcare NHS Foundation Trust in England.
Dr. Kennedy, who was not affiliated with the research, is also supportive of the idea of a psychological subgroup within ECCO.
The peak age for developing mental health disorders found by the study (12-17 years) “is a unique and very sensitive time,” said Sara Mesilhy, MBBS, a gastroenterologist with the Royal College of Physicians in London.
“These results highlight the need for development of early screening psychiatric programs starting from time of diagnosis and continuing on periodic intervals to offer the best management plan for IBD patients, especially those with childhood-onset IBD,” said Dr. Mesilhy, who was not affiliated with the research.
Such programs would “improve the patient’s quality of life, protecting them from a lot of suffering and preventing the bad sequelae for these disorders,” said Dr. Mesilhy. “Moreover, we still need further studies to identify the most efficient monitoring and treatment protocols.”
Dr. Kennedy applauded the researchers for conducting a population-based study because it ensured an adequate cohort size and maximized identification of mental health disorders.
“It was interesting to see that there were a range of conditions where risk was increased, and that males with IBD were at particularly increased risk,” he added.
Researchers’ use of coded primary care data was a study limitation, but it was “appropriately acknowledged by the presenter,” Dr. Kennedy said.
The study was supported by Pfizer. Dr. Russell disclosed he is a consultant and member of a speakers’ bureau for Pfizer outside the submitted work. Dr. Kennedy and Dr. Mesilhy report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECCO 2023
DNA panels could predict endoscopic response to biologics in Crohn’s disease
Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.
Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.
“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.
After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.
DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.
Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.
Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
Methylation methodology
Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).
Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.
Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.
Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.
Key findings
One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.
The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.
“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.
A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.
“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
Promising start
“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.
“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.
Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.
The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.
Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.
A version of this article first appeared on Medscape.com.
Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.
Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.
“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.
After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.
DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.
Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.
Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
Methylation methodology
Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).
Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.
Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.
Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.
Key findings
One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.
The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.
“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.
A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.
“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
Promising start
“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.
“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.
Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.
The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.
Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.
A version of this article first appeared on Medscape.com.
Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.
Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.
“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.
After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.
DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.
Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.
Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
Methylation methodology
Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).
Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.
Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.
Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.
Key findings
One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.
The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.
“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.
A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.
“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
Promising start
“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.
“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.
Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.
The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.
Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.
A version of this article first appeared on Medscape.com.
FROM ECCO 2023
Ileocecal resection possible first-line option in early Crohn’s disease
COPENHAGEN – Half of patients with ileocecal Crohn’s disease who undergo ileocecal resection within a year of diagnosis remain off drug treatment 5 years post procedure, challenging the current paradigm of reserving surgery for complicated Crohn’s disease, show real-world data comparing outcomes of surgery with anti–tumor necrosis factor inhibitor (TNFi) therapy.
“These data show that resection of inflamed bowel in early ileocecal Crohn’s disease effectively resets the clock,” said Manasi Agrawal, MD, of the department of gastroenterology at the Icahn School of Medicine at Mount Sinai, New York, and a research associate with the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen, who presented the findings at the annual congress of the European Crohn’s and Colitis Organisation. “These data are in accordance with the LIR!C study data and suggest that ileocecal resection could be a first-line therapeutic option in early ileal or ileocecal Crohn’s disease that could be discussed with our patients.”
While ileocecal resection is accepted as a therapeutic option in early Crohn’s disease, most clinicians reserve it for complicated disease that is refractory or intolerant to medication.
A radical shift in approach might be justified, said Jean-Frederic Colombel, MD, a study coinvestigator and gastroenterologist at Mount Sinai Hospital.
“These data can be transforming. It confirms that there may be a subset of patients with limited ileal Crohn’s disease that is uncomplicated and in whom surgery may be almost ‘curative’ because after follow-up there was no need for drug therapy. We need to reposition surgery as one possible option at diagnosis in patients with limited Crohn’s disease,” he said.
The 2017 LIR!C trial demonstrated comparable 1-year outcomes with ileocecal resection and anti-TNFi therapy in limited, nonstricturing ileocecal Crohn’s disease. A retrospective analysis of 5-year data from this trial, further reinforced ileocecal resection as a first-line option for limited Crohn’s disease, such that of those patients who underwent resection, 26% continued on anti-TNFi therapy, compared with 38% in those patients who took anti-TNFi therapy only. In addition, no patient in the resection group underwent subsequent surgery, whereas 48% of patients on anti-TNF underwent surgery.
Dr. Agrawal and coinvestigators decided that more conclusive, real-world data were needed and would help to determine whether ileocecal resection offered better patient outcomes than staying on anti-TNFi therapy.
The new findings are based on an analysis of 16,443 adults living with ileal Crohn’s disease and were diagnosed between 2003 and 2018. The data is based on an analysis of nationwide Danish registries. It included individuals who underwent
Ileocecal resection or received anti-TNF drugs within 1 year of diagnosis. Of the 16,443 patients diagnosed with Crohn’s disease over the study period, 1,279 had ileal or ileocecal disease and were included with 581 (3.5%) undergoing resection and 698 (4.2%) anti-TNFi index therapy.
Outcomes were compared between the two groups, and the proportions of individuals initiated on immunomodulator, anti-TNFi therapy, or no therapy at 5 years after their ileocecal resection were determined.
The primary outcome was CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD diagnosis. Crohn’s disease–related hospitalization, systemic corticosteroid use, Crohn’s disease–related surgery or perianal Crohn’s disease occurred in 273 versus 318 people in the ileocecal resection and anti-TNFi therapy groups respectively, equating to a 33% lower risk in the resection group. Of those patients who underwent ileocecal resection, 50.3% were on no treatment 5 years later; 47.5% and 17.1% were on immunomodulators and on anti-TNFi therapy respectively.
Resection was found to be associated with a statistically significant reduced risk of systemic corticosteroid use with an adjusted hazard ratio of 0.71 (95% confidence interval, 0.54-0.92). No statistically significant reduced risk was found for Crohn’s disease-related hospitalization (aHR, 0.79; 95% CI, 0.61-1.01) or perianal Crohn’s disease diagnosis (aHR, 0.70; 95% CI, 0.38-1.30). Adjustments were made for demographic and clinical variables, for example, age, sex, year of treatment, number of hospital contacts for an indication all in the year prior to index treatment.
In comparison with the proportion of resection patients at 5 years who were on no treatment, immunomodulators or anti-TNFi therapy, there are no data on the 5-year outcomes of those patients who began on anti-TNFi therapy, but patients typically continue unless they become intolerant or response starts to fail, Dr. Agrawal said.
Willem Bemelmen, MD, a colorectal surgeon from the University of Amsterdam who served as a moderator after the presentation said: “These results could lead to a paradigm shift in the management of patients with Crohn’s disease. Prior studies gave us early signals that surgery in Crohn’s disease might benefit the patients, but now with these larger scale data, with many patients, we might finally convince gastroenterologists to send patients in for early surgery.”
Dr. Agrawal, Dr. Bemelmen, and Dr. Colombel declared no relevant conflicts of interest.
This article was updated 3/7/23.
COPENHAGEN – Half of patients with ileocecal Crohn’s disease who undergo ileocecal resection within a year of diagnosis remain off drug treatment 5 years post procedure, challenging the current paradigm of reserving surgery for complicated Crohn’s disease, show real-world data comparing outcomes of surgery with anti–tumor necrosis factor inhibitor (TNFi) therapy.
“These data show that resection of inflamed bowel in early ileocecal Crohn’s disease effectively resets the clock,” said Manasi Agrawal, MD, of the department of gastroenterology at the Icahn School of Medicine at Mount Sinai, New York, and a research associate with the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen, who presented the findings at the annual congress of the European Crohn’s and Colitis Organisation. “These data are in accordance with the LIR!C study data and suggest that ileocecal resection could be a first-line therapeutic option in early ileal or ileocecal Crohn’s disease that could be discussed with our patients.”
While ileocecal resection is accepted as a therapeutic option in early Crohn’s disease, most clinicians reserve it for complicated disease that is refractory or intolerant to medication.
A radical shift in approach might be justified, said Jean-Frederic Colombel, MD, a study coinvestigator and gastroenterologist at Mount Sinai Hospital.
“These data can be transforming. It confirms that there may be a subset of patients with limited ileal Crohn’s disease that is uncomplicated and in whom surgery may be almost ‘curative’ because after follow-up there was no need for drug therapy. We need to reposition surgery as one possible option at diagnosis in patients with limited Crohn’s disease,” he said.
The 2017 LIR!C trial demonstrated comparable 1-year outcomes with ileocecal resection and anti-TNFi therapy in limited, nonstricturing ileocecal Crohn’s disease. A retrospective analysis of 5-year data from this trial, further reinforced ileocecal resection as a first-line option for limited Crohn’s disease, such that of those patients who underwent resection, 26% continued on anti-TNFi therapy, compared with 38% in those patients who took anti-TNFi therapy only. In addition, no patient in the resection group underwent subsequent surgery, whereas 48% of patients on anti-TNF underwent surgery.
Dr. Agrawal and coinvestigators decided that more conclusive, real-world data were needed and would help to determine whether ileocecal resection offered better patient outcomes than staying on anti-TNFi therapy.
The new findings are based on an analysis of 16,443 adults living with ileal Crohn’s disease and were diagnosed between 2003 and 2018. The data is based on an analysis of nationwide Danish registries. It included individuals who underwent
Ileocecal resection or received anti-TNF drugs within 1 year of diagnosis. Of the 16,443 patients diagnosed with Crohn’s disease over the study period, 1,279 had ileal or ileocecal disease and were included with 581 (3.5%) undergoing resection and 698 (4.2%) anti-TNFi index therapy.
Outcomes were compared between the two groups, and the proportions of individuals initiated on immunomodulator, anti-TNFi therapy, or no therapy at 5 years after their ileocecal resection were determined.
The primary outcome was CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD diagnosis. Crohn’s disease–related hospitalization, systemic corticosteroid use, Crohn’s disease–related surgery or perianal Crohn’s disease occurred in 273 versus 318 people in the ileocecal resection and anti-TNFi therapy groups respectively, equating to a 33% lower risk in the resection group. Of those patients who underwent ileocecal resection, 50.3% were on no treatment 5 years later; 47.5% and 17.1% were on immunomodulators and on anti-TNFi therapy respectively.
Resection was found to be associated with a statistically significant reduced risk of systemic corticosteroid use with an adjusted hazard ratio of 0.71 (95% confidence interval, 0.54-0.92). No statistically significant reduced risk was found for Crohn’s disease-related hospitalization (aHR, 0.79; 95% CI, 0.61-1.01) or perianal Crohn’s disease diagnosis (aHR, 0.70; 95% CI, 0.38-1.30). Adjustments were made for demographic and clinical variables, for example, age, sex, year of treatment, number of hospital contacts for an indication all in the year prior to index treatment.
In comparison with the proportion of resection patients at 5 years who were on no treatment, immunomodulators or anti-TNFi therapy, there are no data on the 5-year outcomes of those patients who began on anti-TNFi therapy, but patients typically continue unless they become intolerant or response starts to fail, Dr. Agrawal said.
Willem Bemelmen, MD, a colorectal surgeon from the University of Amsterdam who served as a moderator after the presentation said: “These results could lead to a paradigm shift in the management of patients with Crohn’s disease. Prior studies gave us early signals that surgery in Crohn’s disease might benefit the patients, but now with these larger scale data, with many patients, we might finally convince gastroenterologists to send patients in for early surgery.”
Dr. Agrawal, Dr. Bemelmen, and Dr. Colombel declared no relevant conflicts of interest.
This article was updated 3/7/23.
COPENHAGEN – Half of patients with ileocecal Crohn’s disease who undergo ileocecal resection within a year of diagnosis remain off drug treatment 5 years post procedure, challenging the current paradigm of reserving surgery for complicated Crohn’s disease, show real-world data comparing outcomes of surgery with anti–tumor necrosis factor inhibitor (TNFi) therapy.
“These data show that resection of inflamed bowel in early ileocecal Crohn’s disease effectively resets the clock,” said Manasi Agrawal, MD, of the department of gastroenterology at the Icahn School of Medicine at Mount Sinai, New York, and a research associate with the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen, who presented the findings at the annual congress of the European Crohn’s and Colitis Organisation. “These data are in accordance with the LIR!C study data and suggest that ileocecal resection could be a first-line therapeutic option in early ileal or ileocecal Crohn’s disease that could be discussed with our patients.”
While ileocecal resection is accepted as a therapeutic option in early Crohn’s disease, most clinicians reserve it for complicated disease that is refractory or intolerant to medication.
A radical shift in approach might be justified, said Jean-Frederic Colombel, MD, a study coinvestigator and gastroenterologist at Mount Sinai Hospital.
“These data can be transforming. It confirms that there may be a subset of patients with limited ileal Crohn’s disease that is uncomplicated and in whom surgery may be almost ‘curative’ because after follow-up there was no need for drug therapy. We need to reposition surgery as one possible option at diagnosis in patients with limited Crohn’s disease,” he said.
The 2017 LIR!C trial demonstrated comparable 1-year outcomes with ileocecal resection and anti-TNFi therapy in limited, nonstricturing ileocecal Crohn’s disease. A retrospective analysis of 5-year data from this trial, further reinforced ileocecal resection as a first-line option for limited Crohn’s disease, such that of those patients who underwent resection, 26% continued on anti-TNFi therapy, compared with 38% in those patients who took anti-TNFi therapy only. In addition, no patient in the resection group underwent subsequent surgery, whereas 48% of patients on anti-TNF underwent surgery.
Dr. Agrawal and coinvestigators decided that more conclusive, real-world data were needed and would help to determine whether ileocecal resection offered better patient outcomes than staying on anti-TNFi therapy.
The new findings are based on an analysis of 16,443 adults living with ileal Crohn’s disease and were diagnosed between 2003 and 2018. The data is based on an analysis of nationwide Danish registries. It included individuals who underwent
Ileocecal resection or received anti-TNF drugs within 1 year of diagnosis. Of the 16,443 patients diagnosed with Crohn’s disease over the study period, 1,279 had ileal or ileocecal disease and were included with 581 (3.5%) undergoing resection and 698 (4.2%) anti-TNFi index therapy.
Outcomes were compared between the two groups, and the proportions of individuals initiated on immunomodulator, anti-TNFi therapy, or no therapy at 5 years after their ileocecal resection were determined.
The primary outcome was CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD diagnosis. Crohn’s disease–related hospitalization, systemic corticosteroid use, Crohn’s disease–related surgery or perianal Crohn’s disease occurred in 273 versus 318 people in the ileocecal resection and anti-TNFi therapy groups respectively, equating to a 33% lower risk in the resection group. Of those patients who underwent ileocecal resection, 50.3% were on no treatment 5 years later; 47.5% and 17.1% were on immunomodulators and on anti-TNFi therapy respectively.
Resection was found to be associated with a statistically significant reduced risk of systemic corticosteroid use with an adjusted hazard ratio of 0.71 (95% confidence interval, 0.54-0.92). No statistically significant reduced risk was found for Crohn’s disease-related hospitalization (aHR, 0.79; 95% CI, 0.61-1.01) or perianal Crohn’s disease diagnosis (aHR, 0.70; 95% CI, 0.38-1.30). Adjustments were made for demographic and clinical variables, for example, age, sex, year of treatment, number of hospital contacts for an indication all in the year prior to index treatment.
In comparison with the proportion of resection patients at 5 years who were on no treatment, immunomodulators or anti-TNFi therapy, there are no data on the 5-year outcomes of those patients who began on anti-TNFi therapy, but patients typically continue unless they become intolerant or response starts to fail, Dr. Agrawal said.
Willem Bemelmen, MD, a colorectal surgeon from the University of Amsterdam who served as a moderator after the presentation said: “These results could lead to a paradigm shift in the management of patients with Crohn’s disease. Prior studies gave us early signals that surgery in Crohn’s disease might benefit the patients, but now with these larger scale data, with many patients, we might finally convince gastroenterologists to send patients in for early surgery.”
Dr. Agrawal, Dr. Bemelmen, and Dr. Colombel declared no relevant conflicts of interest.
This article was updated 3/7/23.
AT ECCO 2023
Pediatric IBD patients wrestle with lingering gut pain
COPENHAGEN –
“A major finding of our small study was the impact of chronic pain on well-being and emotional health which was particularly significant in vulnerable children moving through adolescence towards adulthood,” said Dhamyanthi Thangarajah, MD, a consultant pediatric gastroenterologist at Chelsea and Westminster Hospital, London, in a presentation at the annual congress of the European Crohn’s and Colitis Organisation.
In the study of 41 children between 10 and 17 years old, chronic pain was found in 80% of participants who had established and extensive disease. Most participants had markers for fecal calprotectin, a sensitive marker for inflammation in the gastrointestinal tract, and others had Crohn’s disease and were prescribed biologics.
No relationship was found between chronic pain and IBD activity, but quality of life scores were negatively impacted in children with chronic pain.
“Moving forward, strategies should target screening for chronic pain in children with IBD and provide psychosocial interventions early on,” Dr. Thangarajah said. “We also need to understand more about internalizing pain and explore mood disorders.”
Many children with IBD also present with chronic abdominal pain, which was the impetus for conducting the study. “Essentially, we wondered whether this was a symptom of active disease, or were we missing something? In adult patients, chronic pain is prevalent, but in children we don’t necessarily screen for chronic pain, although it is part of active disease,” she said.
There is considerable patient and parental anxiety around the nature and origins of the chronic pain, Dr. Thangarajah said.
“We need to understand the prevalence and impact of chronic pain in children and adolescents, and as such we wanted to understand and characterize our cohort,” she said.
Dr. Thangarajah said clinicians tend to be very focused on disease activity and that screening for chronic pain is not usually carried out. “When we look at their clinical indices, the patients seem better, but the fact that it affects emotional health, and we don’t screen for it, means we need psychological help for these pediatric patients,” she said. “Patients need to be able to talk about their pain, and we need to understand if these children are having IBD-type symptoms, and this just isn’t asked about. It would be good to extend this study with a psychologist to understand more about this pain.”
How the study was conducted
The findings are based on the IMPACT III quality of life questionnaire for IBD. Chronic pain was defined as mild, moderate, or severe according to the van Korff scale.
“Patients had extensive and established disease, as expected in a pediatric cohort, the majority of whom were on immunosuppressant biologic drugs [64%-89%]. Among these patients, analgesic use was low, which is part of the education we give parents, and there was no opiate use in children, which differs from adults with IBD,” Dr. Thangarajah said.
A total of 33/41 (80%) of patients had chronic pain, and of these, abdominal chronic pain was most common in 30/33 (90%), joint pain was present in 2/33 (6%), and headache in 1/33, (3%). The majority 26/33 (79%) were on biologic agents, and analgesia use was low at 15/33 (45%). A total of 42% of children across the spectrum of chronic pain severity were on immunomodulators. Comorbidities were present in 42%-57% of patients with mild, and moderate-severe chronic pain respectively.
IBD disease activity in children with chronic pain was compared with those without chronic pain, as defined by Pediatric Crohn’s Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), C-reactive protein (CRP), and faecal calprotectin. No difference was found.
Dr. Thangarajah highlighted the significantly lower quality of life score in children with chronic pain (69 and 51 in mild, and moderate-severe pain subgroups respectively, compared with 81 in those children without chronic pain, P < .05). Specifically, body image showed no difference between children with and without chronic pain (59-65 points across no pain, mild, moderate and severe chronic pain).
Chronic pain patients also commonly reported sleep disturbance with around 66% of patients with chronic pain, compared with around 11% in those without. Anemia was reported in 30% versus 21% respectively. However, nearly half of children with chronic pain had comorbidities 16/33 (48%), and 5/16 (31%) had diagnoses that may be associated with comorbid pain.
Psychosocial support within gastroenterology unavailable
Christine Norton, PhD, professor of nursing at Kings College London, also spoke at the conference on abdominal pain and the well-being of patients with IBD. She said that pain can still be a problem for some patients in remission from IBD.
“In adults we find pain is related to disease activity, however, 40%-50% of patients with IBD remission still report pain. Abdominal pain is dominant but it can be anywhere in the body. This is really poorly addressed in clinical consultations. It’s a ‘don’t ask, don’t tell’ situation where the nurse or doctor would do something if they could, but they just don’t ask the patients,” she said.
If patients volunteer the information that they still have pain during remission, it might get dismissed as irritable bowel syndrome (IBS), Dr. Norton said. “Some patients do fulfill these criteria for IBS, but it still needs to be managed. Here at ECCO, the focus is on getting patients into deep remission and inflammation under tight control, but what do we do with the jangling pain nerves although there’s nothing apparently triggering them, the gut-brain sensitivity – it’s so hard to live with it. They need support,” she said.
Dr. Norton said clinicians need a better way to validate chronic pain. “Sometimes people don’t feel believed, but even if the doctor believes them, they don’t know what to do anyway. There’s very few places with psychological support within the field of gastroenterology. Do we educate the gastroenterologist in this aspect? Do we develop the skills of IBD nurses?”
Dr. Thangarajah and Dr. Norton have no disclosures to declare.
COPENHAGEN –
“A major finding of our small study was the impact of chronic pain on well-being and emotional health which was particularly significant in vulnerable children moving through adolescence towards adulthood,” said Dhamyanthi Thangarajah, MD, a consultant pediatric gastroenterologist at Chelsea and Westminster Hospital, London, in a presentation at the annual congress of the European Crohn’s and Colitis Organisation.
In the study of 41 children between 10 and 17 years old, chronic pain was found in 80% of participants who had established and extensive disease. Most participants had markers for fecal calprotectin, a sensitive marker for inflammation in the gastrointestinal tract, and others had Crohn’s disease and were prescribed biologics.
No relationship was found between chronic pain and IBD activity, but quality of life scores were negatively impacted in children with chronic pain.
“Moving forward, strategies should target screening for chronic pain in children with IBD and provide psychosocial interventions early on,” Dr. Thangarajah said. “We also need to understand more about internalizing pain and explore mood disorders.”
Many children with IBD also present with chronic abdominal pain, which was the impetus for conducting the study. “Essentially, we wondered whether this was a symptom of active disease, or were we missing something? In adult patients, chronic pain is prevalent, but in children we don’t necessarily screen for chronic pain, although it is part of active disease,” she said.
There is considerable patient and parental anxiety around the nature and origins of the chronic pain, Dr. Thangarajah said.
“We need to understand the prevalence and impact of chronic pain in children and adolescents, and as such we wanted to understand and characterize our cohort,” she said.
Dr. Thangarajah said clinicians tend to be very focused on disease activity and that screening for chronic pain is not usually carried out. “When we look at their clinical indices, the patients seem better, but the fact that it affects emotional health, and we don’t screen for it, means we need psychological help for these pediatric patients,” she said. “Patients need to be able to talk about their pain, and we need to understand if these children are having IBD-type symptoms, and this just isn’t asked about. It would be good to extend this study with a psychologist to understand more about this pain.”
How the study was conducted
The findings are based on the IMPACT III quality of life questionnaire for IBD. Chronic pain was defined as mild, moderate, or severe according to the van Korff scale.
“Patients had extensive and established disease, as expected in a pediatric cohort, the majority of whom were on immunosuppressant biologic drugs [64%-89%]. Among these patients, analgesic use was low, which is part of the education we give parents, and there was no opiate use in children, which differs from adults with IBD,” Dr. Thangarajah said.
A total of 33/41 (80%) of patients had chronic pain, and of these, abdominal chronic pain was most common in 30/33 (90%), joint pain was present in 2/33 (6%), and headache in 1/33, (3%). The majority 26/33 (79%) were on biologic agents, and analgesia use was low at 15/33 (45%). A total of 42% of children across the spectrum of chronic pain severity were on immunomodulators. Comorbidities were present in 42%-57% of patients with mild, and moderate-severe chronic pain respectively.
IBD disease activity in children with chronic pain was compared with those without chronic pain, as defined by Pediatric Crohn’s Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), C-reactive protein (CRP), and faecal calprotectin. No difference was found.
Dr. Thangarajah highlighted the significantly lower quality of life score in children with chronic pain (69 and 51 in mild, and moderate-severe pain subgroups respectively, compared with 81 in those children without chronic pain, P < .05). Specifically, body image showed no difference between children with and without chronic pain (59-65 points across no pain, mild, moderate and severe chronic pain).
Chronic pain patients also commonly reported sleep disturbance with around 66% of patients with chronic pain, compared with around 11% in those without. Anemia was reported in 30% versus 21% respectively. However, nearly half of children with chronic pain had comorbidities 16/33 (48%), and 5/16 (31%) had diagnoses that may be associated with comorbid pain.
Psychosocial support within gastroenterology unavailable
Christine Norton, PhD, professor of nursing at Kings College London, also spoke at the conference on abdominal pain and the well-being of patients with IBD. She said that pain can still be a problem for some patients in remission from IBD.
“In adults we find pain is related to disease activity, however, 40%-50% of patients with IBD remission still report pain. Abdominal pain is dominant but it can be anywhere in the body. This is really poorly addressed in clinical consultations. It’s a ‘don’t ask, don’t tell’ situation where the nurse or doctor would do something if they could, but they just don’t ask the patients,” she said.
If patients volunteer the information that they still have pain during remission, it might get dismissed as irritable bowel syndrome (IBS), Dr. Norton said. “Some patients do fulfill these criteria for IBS, but it still needs to be managed. Here at ECCO, the focus is on getting patients into deep remission and inflammation under tight control, but what do we do with the jangling pain nerves although there’s nothing apparently triggering them, the gut-brain sensitivity – it’s so hard to live with it. They need support,” she said.
Dr. Norton said clinicians need a better way to validate chronic pain. “Sometimes people don’t feel believed, but even if the doctor believes them, they don’t know what to do anyway. There’s very few places with psychological support within the field of gastroenterology. Do we educate the gastroenterologist in this aspect? Do we develop the skills of IBD nurses?”
Dr. Thangarajah and Dr. Norton have no disclosures to declare.
COPENHAGEN –
“A major finding of our small study was the impact of chronic pain on well-being and emotional health which was particularly significant in vulnerable children moving through adolescence towards adulthood,” said Dhamyanthi Thangarajah, MD, a consultant pediatric gastroenterologist at Chelsea and Westminster Hospital, London, in a presentation at the annual congress of the European Crohn’s and Colitis Organisation.
In the study of 41 children between 10 and 17 years old, chronic pain was found in 80% of participants who had established and extensive disease. Most participants had markers for fecal calprotectin, a sensitive marker for inflammation in the gastrointestinal tract, and others had Crohn’s disease and were prescribed biologics.
No relationship was found between chronic pain and IBD activity, but quality of life scores were negatively impacted in children with chronic pain.
“Moving forward, strategies should target screening for chronic pain in children with IBD and provide psychosocial interventions early on,” Dr. Thangarajah said. “We also need to understand more about internalizing pain and explore mood disorders.”
Many children with IBD also present with chronic abdominal pain, which was the impetus for conducting the study. “Essentially, we wondered whether this was a symptom of active disease, or were we missing something? In adult patients, chronic pain is prevalent, but in children we don’t necessarily screen for chronic pain, although it is part of active disease,” she said.
There is considerable patient and parental anxiety around the nature and origins of the chronic pain, Dr. Thangarajah said.
“We need to understand the prevalence and impact of chronic pain in children and adolescents, and as such we wanted to understand and characterize our cohort,” she said.
Dr. Thangarajah said clinicians tend to be very focused on disease activity and that screening for chronic pain is not usually carried out. “When we look at their clinical indices, the patients seem better, but the fact that it affects emotional health, and we don’t screen for it, means we need psychological help for these pediatric patients,” she said. “Patients need to be able to talk about their pain, and we need to understand if these children are having IBD-type symptoms, and this just isn’t asked about. It would be good to extend this study with a psychologist to understand more about this pain.”
How the study was conducted
The findings are based on the IMPACT III quality of life questionnaire for IBD. Chronic pain was defined as mild, moderate, or severe according to the van Korff scale.
“Patients had extensive and established disease, as expected in a pediatric cohort, the majority of whom were on immunosuppressant biologic drugs [64%-89%]. Among these patients, analgesic use was low, which is part of the education we give parents, and there was no opiate use in children, which differs from adults with IBD,” Dr. Thangarajah said.
A total of 33/41 (80%) of patients had chronic pain, and of these, abdominal chronic pain was most common in 30/33 (90%), joint pain was present in 2/33 (6%), and headache in 1/33, (3%). The majority 26/33 (79%) were on biologic agents, and analgesia use was low at 15/33 (45%). A total of 42% of children across the spectrum of chronic pain severity were on immunomodulators. Comorbidities were present in 42%-57% of patients with mild, and moderate-severe chronic pain respectively.
IBD disease activity in children with chronic pain was compared with those without chronic pain, as defined by Pediatric Crohn’s Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), C-reactive protein (CRP), and faecal calprotectin. No difference was found.
Dr. Thangarajah highlighted the significantly lower quality of life score in children with chronic pain (69 and 51 in mild, and moderate-severe pain subgroups respectively, compared with 81 in those children without chronic pain, P < .05). Specifically, body image showed no difference between children with and without chronic pain (59-65 points across no pain, mild, moderate and severe chronic pain).
Chronic pain patients also commonly reported sleep disturbance with around 66% of patients with chronic pain, compared with around 11% in those without. Anemia was reported in 30% versus 21% respectively. However, nearly half of children with chronic pain had comorbidities 16/33 (48%), and 5/16 (31%) had diagnoses that may be associated with comorbid pain.
Psychosocial support within gastroenterology unavailable
Christine Norton, PhD, professor of nursing at Kings College London, also spoke at the conference on abdominal pain and the well-being of patients with IBD. She said that pain can still be a problem for some patients in remission from IBD.
“In adults we find pain is related to disease activity, however, 40%-50% of patients with IBD remission still report pain. Abdominal pain is dominant but it can be anywhere in the body. This is really poorly addressed in clinical consultations. It’s a ‘don’t ask, don’t tell’ situation where the nurse or doctor would do something if they could, but they just don’t ask the patients,” she said.
If patients volunteer the information that they still have pain during remission, it might get dismissed as irritable bowel syndrome (IBS), Dr. Norton said. “Some patients do fulfill these criteria for IBS, but it still needs to be managed. Here at ECCO, the focus is on getting patients into deep remission and inflammation under tight control, but what do we do with the jangling pain nerves although there’s nothing apparently triggering them, the gut-brain sensitivity – it’s so hard to live with it. They need support,” she said.
Dr. Norton said clinicians need a better way to validate chronic pain. “Sometimes people don’t feel believed, but even if the doctor believes them, they don’t know what to do anyway. There’s very few places with psychological support within the field of gastroenterology. Do we educate the gastroenterologist in this aspect? Do we develop the skills of IBD nurses?”
Dr. Thangarajah and Dr. Norton have no disclosures to declare.
AT ECCO 2023
DNA panels could predict endoscopic response to biologics in Crohn’s disease
Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.
Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.
“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.
After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.
DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.
Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.
Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
Methylation methodology
Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).
Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.
Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.
Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.
Key findings
One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.
The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.
“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.
A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.
“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
Promising start
“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.
“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.
Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.
The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.
Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.
“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.
After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.
DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.
Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.
Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
Methylation methodology
Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).
Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.
Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.
Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.
Key findings
One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.
The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.
“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.
A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.
“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
Promising start
“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.
“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.
Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.
The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.
Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.
“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.
After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.
DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.
Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.
Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
Methylation methodology
Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).
Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.
Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.
Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.
Key findings
One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.
The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.
“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.
A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.
“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
Promising start
“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.
“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.
Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.
The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECCO 2023
IBD: More patients on vedolizumab vs. anti-TNFs at 2 years
COPENHAGEN – , according to the first meta-analysis of their real-world effectiveness.
The results mostly applied to bionaive subjects, and the benefit of vedolizumab over both TNFi’s – infliximab (Remicade) and adalimumab (Humira), was more evident in ulcerative colitis, compared with Crohn’s disease, noted the researchers, led by Tsz Hong Yiu, MD, a clinician and researcher at the University of Sydney.
“It appears that patients are more likely to stay on vedolizumab than either infliximab or adalimumab, especially in bionaive patients, which could suggest either a better tolerance to the treatment or a better response,” Dr. Yiu said in an interview at the annual Congress of the European Crohn’s and Colitis Organisation.
The 2-year follow up data were particularly encouraging, noted Dr. Yiu, with more patients persisting on vedolizumab than both anti-TNF alpha drugs overall with respect to both ulcerative colitis and Crohn’s disease.
In a head-to-head comparison, 15% more patients stayed on vedolizumab than anti-TNF alpha drugs overall, at 1-year follow-up for both ulcerative colitis and Crohn’s disease (risk ratio, 1.15). At 2 years of follow-up, 12% more patients remained on vedolizumab in comparison with anti-TNF alpha drugs overall (RR, 1.12), again for both forms of inflammatory bowel disease (IBD).
“This may provide early evidence that supports vedolizumab as a first-line biologic agent for inpatients with inflammatory bowel disease,” said Dr. Yiu, noting that further research was required to validate the correlation of persistence with clinical effectiveness.
Adding comment on the motivation for the study, senior author Rupert Leong, MD, a gastroenterologist at Concord RepatriaKon General Hospital, Sydney, said, “We wanted to identify the drug with the highest effectiveness, which is the real-world benefit of the drug to patients, rather than efficacy, which refers to clinical trial data.”
“Importantly, clinical trial data are usually only 1 year, whereas persistence collects data often for several years. This is relevant in chronic diseases that can affect patients over several decades, because the true benefit of a drug cannot be implied from a short-term clinical trial,” he explained.
Persistence was chosen as the primary end-point because it is a measure that incorporates a drug’s efficacy and side-effect profile but also the patient’s perspective, added Dr. Yiu. “So, a patient may value mild side effects over treatment effectiveness and decide to cease treatment.”
A prior meta-analysis looking at loss of response found that 33% of people taking infliximab and 41% of people taking adalimumab became resistant to the biologics after a median follow up of 1 year. “The most common cause of loss of response to anti-TNF inhibitors is due to immunogenicity,” remarked Dr. Yiu. “These findings suggested that alternative biologics with high effectiveness should be considered.”
Data from the 2019 VARSITY study also informed the researchers’ decision to conduct a real-world study. VARSITY investigators found vedolizumab had increased efficacy over adalimumab in ulcerative colitis, however, data on the real-world effectiveness of vedolizumab, compared with adalimumab and infliximab, in both ulcerative colitis and Crohn’s disease remained unknown.
Dr. Leong pointed out the difficulty in selecting the correct treatment given the increasing numbers of biological agents available. “The paucity of head-to-head studies meant use of cohort studies is considered both relevant and informative, not least because long-term follow-up data can reveal secondary loss of response of these monoclonal antibodies, while pooling data further increases the statistical power and determines consistency.”
As such, the researchers conducted a systematic review and meta-analysis of six observational studies evaluating persistence, as a surrogate marker for clinical response, of vedolizumab versus infliximab and adalimumab among participants aged over 18 years with a diagnosis of either ulcerative colitis or Crohn’s disease from 2017 to July 2022.
Overall, the study found that 1-year persistence of vedolizumab was 71.2% in ulcerative colitis and 76% in Crohn’s disease, which was significantly higher than with infliximab (56.4% in ulcerative colitis, 53.7% in Crohn’s disease), and likewise with adalimumab (53.7% in ulcerative colitis, 55.6% in Crohn’s disease).
Results of 2-year persistence were pooled from four studies and found that vedolizumab had a 2-year persistence of 66% in ulcerative colitis and 61% in Crohn’s disease. By comparison, infliximab had a persistence of 49.7% for ulcerative colitis and 59.1% for Crohn’s disease, and adalimumab had a persistence of 31.4% for ulcerative colitis and 56% for Crohn’s disease).
In ulcerative colitis specifically, vedolizumab performed better than both adalimumab and infliximab with an RR of 1.41 (95% confidence interval, 1.14-1.74) and 1.15 (95% CI, 1.06-1.25) respectively, and an RR of 1.23 (95% CI, 1.14-1.33) was generated when adalimumab and infliximab results were combined after 1 year of follow-up.
In Crohn’s disease specifically, vedolizumab had a slightly higher 1-year persistence over anti-TNF inhibitors combined (RR, 1.10; 95% CI, 1.02-1.19), but there were insufficient data to support individual analysis.
In a subgroup of bionaive patients, vedolizumab had a higher 1-year persistence (RR, 1.14; 95% CI, 1.07-1.22) but did not show a statistically significant advantage in bioexperienced patients (RR, 1.04; 95% CI, 0.80-1.35), compared with anti-TNF inhibitors.
Dr. Yiu remarked that they were unable to identify any randomized controlled trials (RCTs) directly comparing infliximab versus vedolizumab in IBD at the time of their systematic review. However, he drew attention to a recent research article that compared the effectiveness, persistence, and side-effect profile of vedolizumab and infliximab in a small cohort of ulcerative colitis patients. “ In this study, vedolizumab showed overall superiority over infliximab, which is in keeping with our study’s findings.”
Commenting on the study, Viraj Kariyawasam, MD, gastroenterologist and head of IBD at Blacktown and Mount Druitt hospital in Sydney, said the findings were “very important in defining the place of vedolizumab in the treatment of ulcerative colitis, and more so in Crohn’s disease.”
“Despite vedolizumab being considered a lower-efficacy drug, compared to infliximab, in Crohn’s disease by most practicing clinicians, and still favoring anti-TNF in the treatment of Crohn’s disease, the study highlights the superior persistence of vedolizumab,” he said in an interview.
“This is likely associated with efficacy over the two most used anti-TNF agents. With the knowledge we have about reduced efficacy of vedolizumab after the use of anti-TNF, or as a second- or third-line agent, and its superior persistence as a first-line biologic with already published safety data, vedolizumab should be considered and preferred as a first-line agent in the treatment of both ulcerative colitis and Crohn’s disease.”
Dr. Yiu has declared no conflicts of interest. Dr. Leong declares he is an advisory board member of AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda; research grant recipient of Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant University of Sydney. One coauthor is an advisory board member of AbbVie and has received speaker fees from AbbVie and Takeda. Dr. Kariyawasam has educational grants and/or speaker fees from Janssen, AbbVie, and Takeda.
COPENHAGEN – , according to the first meta-analysis of their real-world effectiveness.
The results mostly applied to bionaive subjects, and the benefit of vedolizumab over both TNFi’s – infliximab (Remicade) and adalimumab (Humira), was more evident in ulcerative colitis, compared with Crohn’s disease, noted the researchers, led by Tsz Hong Yiu, MD, a clinician and researcher at the University of Sydney.
“It appears that patients are more likely to stay on vedolizumab than either infliximab or adalimumab, especially in bionaive patients, which could suggest either a better tolerance to the treatment or a better response,” Dr. Yiu said in an interview at the annual Congress of the European Crohn’s and Colitis Organisation.
The 2-year follow up data were particularly encouraging, noted Dr. Yiu, with more patients persisting on vedolizumab than both anti-TNF alpha drugs overall with respect to both ulcerative colitis and Crohn’s disease.
In a head-to-head comparison, 15% more patients stayed on vedolizumab than anti-TNF alpha drugs overall, at 1-year follow-up for both ulcerative colitis and Crohn’s disease (risk ratio, 1.15). At 2 years of follow-up, 12% more patients remained on vedolizumab in comparison with anti-TNF alpha drugs overall (RR, 1.12), again for both forms of inflammatory bowel disease (IBD).
“This may provide early evidence that supports vedolizumab as a first-line biologic agent for inpatients with inflammatory bowel disease,” said Dr. Yiu, noting that further research was required to validate the correlation of persistence with clinical effectiveness.
Adding comment on the motivation for the study, senior author Rupert Leong, MD, a gastroenterologist at Concord RepatriaKon General Hospital, Sydney, said, “We wanted to identify the drug with the highest effectiveness, which is the real-world benefit of the drug to patients, rather than efficacy, which refers to clinical trial data.”
“Importantly, clinical trial data are usually only 1 year, whereas persistence collects data often for several years. This is relevant in chronic diseases that can affect patients over several decades, because the true benefit of a drug cannot be implied from a short-term clinical trial,” he explained.
Persistence was chosen as the primary end-point because it is a measure that incorporates a drug’s efficacy and side-effect profile but also the patient’s perspective, added Dr. Yiu. “So, a patient may value mild side effects over treatment effectiveness and decide to cease treatment.”
A prior meta-analysis looking at loss of response found that 33% of people taking infliximab and 41% of people taking adalimumab became resistant to the biologics after a median follow up of 1 year. “The most common cause of loss of response to anti-TNF inhibitors is due to immunogenicity,” remarked Dr. Yiu. “These findings suggested that alternative biologics with high effectiveness should be considered.”
Data from the 2019 VARSITY study also informed the researchers’ decision to conduct a real-world study. VARSITY investigators found vedolizumab had increased efficacy over adalimumab in ulcerative colitis, however, data on the real-world effectiveness of vedolizumab, compared with adalimumab and infliximab, in both ulcerative colitis and Crohn’s disease remained unknown.
Dr. Leong pointed out the difficulty in selecting the correct treatment given the increasing numbers of biological agents available. “The paucity of head-to-head studies meant use of cohort studies is considered both relevant and informative, not least because long-term follow-up data can reveal secondary loss of response of these monoclonal antibodies, while pooling data further increases the statistical power and determines consistency.”
As such, the researchers conducted a systematic review and meta-analysis of six observational studies evaluating persistence, as a surrogate marker for clinical response, of vedolizumab versus infliximab and adalimumab among participants aged over 18 years with a diagnosis of either ulcerative colitis or Crohn’s disease from 2017 to July 2022.
Overall, the study found that 1-year persistence of vedolizumab was 71.2% in ulcerative colitis and 76% in Crohn’s disease, which was significantly higher than with infliximab (56.4% in ulcerative colitis, 53.7% in Crohn’s disease), and likewise with adalimumab (53.7% in ulcerative colitis, 55.6% in Crohn’s disease).
Results of 2-year persistence were pooled from four studies and found that vedolizumab had a 2-year persistence of 66% in ulcerative colitis and 61% in Crohn’s disease. By comparison, infliximab had a persistence of 49.7% for ulcerative colitis and 59.1% for Crohn’s disease, and adalimumab had a persistence of 31.4% for ulcerative colitis and 56% for Crohn’s disease).
In ulcerative colitis specifically, vedolizumab performed better than both adalimumab and infliximab with an RR of 1.41 (95% confidence interval, 1.14-1.74) and 1.15 (95% CI, 1.06-1.25) respectively, and an RR of 1.23 (95% CI, 1.14-1.33) was generated when adalimumab and infliximab results were combined after 1 year of follow-up.
In Crohn’s disease specifically, vedolizumab had a slightly higher 1-year persistence over anti-TNF inhibitors combined (RR, 1.10; 95% CI, 1.02-1.19), but there were insufficient data to support individual analysis.
In a subgroup of bionaive patients, vedolizumab had a higher 1-year persistence (RR, 1.14; 95% CI, 1.07-1.22) but did not show a statistically significant advantage in bioexperienced patients (RR, 1.04; 95% CI, 0.80-1.35), compared with anti-TNF inhibitors.
Dr. Yiu remarked that they were unable to identify any randomized controlled trials (RCTs) directly comparing infliximab versus vedolizumab in IBD at the time of their systematic review. However, he drew attention to a recent research article that compared the effectiveness, persistence, and side-effect profile of vedolizumab and infliximab in a small cohort of ulcerative colitis patients. “ In this study, vedolizumab showed overall superiority over infliximab, which is in keeping with our study’s findings.”
Commenting on the study, Viraj Kariyawasam, MD, gastroenterologist and head of IBD at Blacktown and Mount Druitt hospital in Sydney, said the findings were “very important in defining the place of vedolizumab in the treatment of ulcerative colitis, and more so in Crohn’s disease.”
“Despite vedolizumab being considered a lower-efficacy drug, compared to infliximab, in Crohn’s disease by most practicing clinicians, and still favoring anti-TNF in the treatment of Crohn’s disease, the study highlights the superior persistence of vedolizumab,” he said in an interview.
“This is likely associated with efficacy over the two most used anti-TNF agents. With the knowledge we have about reduced efficacy of vedolizumab after the use of anti-TNF, or as a second- or third-line agent, and its superior persistence as a first-line biologic with already published safety data, vedolizumab should be considered and preferred as a first-line agent in the treatment of both ulcerative colitis and Crohn’s disease.”
Dr. Yiu has declared no conflicts of interest. Dr. Leong declares he is an advisory board member of AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda; research grant recipient of Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant University of Sydney. One coauthor is an advisory board member of AbbVie and has received speaker fees from AbbVie and Takeda. Dr. Kariyawasam has educational grants and/or speaker fees from Janssen, AbbVie, and Takeda.
COPENHAGEN – , according to the first meta-analysis of their real-world effectiveness.
The results mostly applied to bionaive subjects, and the benefit of vedolizumab over both TNFi’s – infliximab (Remicade) and adalimumab (Humira), was more evident in ulcerative colitis, compared with Crohn’s disease, noted the researchers, led by Tsz Hong Yiu, MD, a clinician and researcher at the University of Sydney.
“It appears that patients are more likely to stay on vedolizumab than either infliximab or adalimumab, especially in bionaive patients, which could suggest either a better tolerance to the treatment or a better response,” Dr. Yiu said in an interview at the annual Congress of the European Crohn’s and Colitis Organisation.
The 2-year follow up data were particularly encouraging, noted Dr. Yiu, with more patients persisting on vedolizumab than both anti-TNF alpha drugs overall with respect to both ulcerative colitis and Crohn’s disease.
In a head-to-head comparison, 15% more patients stayed on vedolizumab than anti-TNF alpha drugs overall, at 1-year follow-up for both ulcerative colitis and Crohn’s disease (risk ratio, 1.15). At 2 years of follow-up, 12% more patients remained on vedolizumab in comparison with anti-TNF alpha drugs overall (RR, 1.12), again for both forms of inflammatory bowel disease (IBD).
“This may provide early evidence that supports vedolizumab as a first-line biologic agent for inpatients with inflammatory bowel disease,” said Dr. Yiu, noting that further research was required to validate the correlation of persistence with clinical effectiveness.
Adding comment on the motivation for the study, senior author Rupert Leong, MD, a gastroenterologist at Concord RepatriaKon General Hospital, Sydney, said, “We wanted to identify the drug with the highest effectiveness, which is the real-world benefit of the drug to patients, rather than efficacy, which refers to clinical trial data.”
“Importantly, clinical trial data are usually only 1 year, whereas persistence collects data often for several years. This is relevant in chronic diseases that can affect patients over several decades, because the true benefit of a drug cannot be implied from a short-term clinical trial,” he explained.
Persistence was chosen as the primary end-point because it is a measure that incorporates a drug’s efficacy and side-effect profile but also the patient’s perspective, added Dr. Yiu. “So, a patient may value mild side effects over treatment effectiveness and decide to cease treatment.”
A prior meta-analysis looking at loss of response found that 33% of people taking infliximab and 41% of people taking adalimumab became resistant to the biologics after a median follow up of 1 year. “The most common cause of loss of response to anti-TNF inhibitors is due to immunogenicity,” remarked Dr. Yiu. “These findings suggested that alternative biologics with high effectiveness should be considered.”
Data from the 2019 VARSITY study also informed the researchers’ decision to conduct a real-world study. VARSITY investigators found vedolizumab had increased efficacy over adalimumab in ulcerative colitis, however, data on the real-world effectiveness of vedolizumab, compared with adalimumab and infliximab, in both ulcerative colitis and Crohn’s disease remained unknown.
Dr. Leong pointed out the difficulty in selecting the correct treatment given the increasing numbers of biological agents available. “The paucity of head-to-head studies meant use of cohort studies is considered both relevant and informative, not least because long-term follow-up data can reveal secondary loss of response of these monoclonal antibodies, while pooling data further increases the statistical power and determines consistency.”
As such, the researchers conducted a systematic review and meta-analysis of six observational studies evaluating persistence, as a surrogate marker for clinical response, of vedolizumab versus infliximab and adalimumab among participants aged over 18 years with a diagnosis of either ulcerative colitis or Crohn’s disease from 2017 to July 2022.
Overall, the study found that 1-year persistence of vedolizumab was 71.2% in ulcerative colitis and 76% in Crohn’s disease, which was significantly higher than with infliximab (56.4% in ulcerative colitis, 53.7% in Crohn’s disease), and likewise with adalimumab (53.7% in ulcerative colitis, 55.6% in Crohn’s disease).
Results of 2-year persistence were pooled from four studies and found that vedolizumab had a 2-year persistence of 66% in ulcerative colitis and 61% in Crohn’s disease. By comparison, infliximab had a persistence of 49.7% for ulcerative colitis and 59.1% for Crohn’s disease, and adalimumab had a persistence of 31.4% for ulcerative colitis and 56% for Crohn’s disease).
In ulcerative colitis specifically, vedolizumab performed better than both adalimumab and infliximab with an RR of 1.41 (95% confidence interval, 1.14-1.74) and 1.15 (95% CI, 1.06-1.25) respectively, and an RR of 1.23 (95% CI, 1.14-1.33) was generated when adalimumab and infliximab results were combined after 1 year of follow-up.
In Crohn’s disease specifically, vedolizumab had a slightly higher 1-year persistence over anti-TNF inhibitors combined (RR, 1.10; 95% CI, 1.02-1.19), but there were insufficient data to support individual analysis.
In a subgroup of bionaive patients, vedolizumab had a higher 1-year persistence (RR, 1.14; 95% CI, 1.07-1.22) but did not show a statistically significant advantage in bioexperienced patients (RR, 1.04; 95% CI, 0.80-1.35), compared with anti-TNF inhibitors.
Dr. Yiu remarked that they were unable to identify any randomized controlled trials (RCTs) directly comparing infliximab versus vedolizumab in IBD at the time of their systematic review. However, he drew attention to a recent research article that compared the effectiveness, persistence, and side-effect profile of vedolizumab and infliximab in a small cohort of ulcerative colitis patients. “ In this study, vedolizumab showed overall superiority over infliximab, which is in keeping with our study’s findings.”
Commenting on the study, Viraj Kariyawasam, MD, gastroenterologist and head of IBD at Blacktown and Mount Druitt hospital in Sydney, said the findings were “very important in defining the place of vedolizumab in the treatment of ulcerative colitis, and more so in Crohn’s disease.”
“Despite vedolizumab being considered a lower-efficacy drug, compared to infliximab, in Crohn’s disease by most practicing clinicians, and still favoring anti-TNF in the treatment of Crohn’s disease, the study highlights the superior persistence of vedolizumab,” he said in an interview.
“This is likely associated with efficacy over the two most used anti-TNF agents. With the knowledge we have about reduced efficacy of vedolizumab after the use of anti-TNF, or as a second- or third-line agent, and its superior persistence as a first-line biologic with already published safety data, vedolizumab should be considered and preferred as a first-line agent in the treatment of both ulcerative colitis and Crohn’s disease.”
Dr. Yiu has declared no conflicts of interest. Dr. Leong declares he is an advisory board member of AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda; research grant recipient of Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant University of Sydney. One coauthor is an advisory board member of AbbVie and has received speaker fees from AbbVie and Takeda. Dr. Kariyawasam has educational grants and/or speaker fees from Janssen, AbbVie, and Takeda.
AT ECCO 2023