TBD Meeting (3208-22)

PHILADELPHIA – For patients with rheumatoid arthritis who are already at increased risk for major adverse cardiovascular events (MACE), NSAIDs may be safer than opioids, results of a new-user active comparator study suggest.

Among 6,866 patients with RA who started on opioids and 13,698 patients who started on NSAIDs for pain, the use of both weak and strong opioids was associated with a 33% increase in risk for all-cause mortality and a trend toward higher rates of venous thromboembolism (VTE), compared with NSAID use, reported Gulsen Ozen, MD, of the University of Nebraska Medical Center, Omaha.

Neil Osterweil/MDedge News

“Pain in RA is a very complex process, and we know that it’s not solely dependent on the disease activity, but there is no evidence that opioids have any benefit in long-term pain management, and it can even cause hyperalgesia. And as we show, it’s not safer than NSAIDs,” she said in an oral abstract session at the annual meeting of the American College of Rheumatology.

She stressed that patients should be assessed for non-RA causes of pain and should use nonpharmacologic methods when possible.

“If a pharmacological treatment is needed and NSAIDs are contraindicated, the lowest possible dose of weak opioids can be used for a very limited time for acute pain only,” she said.
 

Pain despite disease control

Even when their disease is well controlled, approximately 60% of patients with RA still report pain. NSAIDs are commonly used to treat pain in patients with RA, but they are associated with modest increases in risk for cardiovascular disease (CVD), gastrointestinal bleeding, renal injury, and hypertension.

Some providers are leery of NSAIDs and will instead prescribe either regular or intermittent opioids for pain control in their patients.

Disease-modifying antirheumatic drugs have only minimal pain-relieving benefits, “and even worse, opioids can delay initiation of DMARDs in RA,” Dr. Ozen said.

Opioids have been shown to increase oxidative stress, platelet aggregation, and myocardial fibrosis, as well as hypogonadism, weight gain, and CVD risk factors.

There is little evidence, however, on whether opioids are associated with cardiovascular events in patients with RA. This dearth of data prompted Dr. Ozen and colleagues to study the relative risks for MACE in patients with RA starting on opioids or NSAIDs for pain.

Matched cohorts

They used data from FORWARD, a joint Canadian and U.S. databank for rheumatic diseases, to conduct a new-user active comparator cohort study. The cohort included adults with RA without cancer who participated in FORWARD for a minimum of 1 year between 1998 and 2021.

The patients were followed either from drug initiation until 3 months after the end of treatment, defined as either discontinuation or a switch to a different analgesic, end of study follow-up, or the development of a MACE outcome.

The investigators used propensity score matching to compare each opioid initiator with two NSAID initiators. The participants were matched by age, sex, body mass index, smoking, alcohol, RA duration, disease activity, Health Assessment Questionnaire, visual analog scale for pain, joint surgeries, prior CVD and VTE, hypertension, diabetes, rheumatic diseases comorbidity index, osteoporosis/fractures, thyroid, chronic liver, kidney, lung and mental health diseases, hospitalizations, 36-Item Short Form Health Survey scores, and sleep scores.

The two groups were well matched, except for a slightly higher incidence of VTE in opioid initiators, although incidence rates were low in both groups (0.9% vs. 0.6% of NSAID initiators).
 

Higher death rate in opioid users

The incidence rate of MACE among opioid initiators was 20.6% versus18.9% among NSAID initiators, a difference that was not statistically significant. There were also no significant differences in incidence rates of the individual components of the MACE composite outcome: myocardial infarction, stroke, heart failure, CVD death, or VTE.

There were, however, significantly more deaths from any cause among patients in the opioid group, with an incidence rate of 13.5% versus 10.8% in the NSAID group.

An analysis of the associaion of drug type with outcomes, adjusted for propensity score weight and prior VTE showed that patients on opioids had a statistically significant hazard ratio for death from any cause of 1.33 (95% confidence interval, 1.06-1.67).

The increased risk for all-cause mortality occurred both in patients starting on weak opioids (hydrocodone, tramadol, codeine, pentazocine, and propoxyphene) and on strong opioids (hydromorphone, dihydromorphinone, oxymorphone, butorphanol, methadone, morphine, oxycodone, meperidine, and fentanyl).

As noted before, there was a trend toward an increased risk for VTE among opioid initiators, but this was not statistically significant.

The increase in risk was higher among patients on strong versus weak opioids, suggesting a dose-dependent relationship, Dr. Ozen said.

A comparison of opioid-associated risk for all-cause mortality vs. NSAIDs according to type (nonselective or selective) showed that most of the increase in risk was relative to selective cycloxygenase-2 inhibitors.

‘Beautiful’ analysis

“This is a beautiful piece of analysis on a really difficult question to address because the confounding is really hard to unpick,” commented James Galloway, MBBS, deputy head of the center for rheumatic diseases at King’s College London and consulting rheumatologist at King’s College Hospital, also in London.

“The headline message is that there didn’t appear to be a clear signal that NSAIDs were worse, which is what I thought the preexisting view might have been. And so, people may have paradoxically prescribed opioids in favor of NSAIDs in a person with cardiovascular risk,” he said in an interview. Dr. Galloway attended the oral abstract session but was not involved in the study.

The study was supported by a grant to Dr. Ozen from the Rheumatology Research Foundation. Dr. Galloway reported having no relevant disclosures.

PHILADELPHIA – For patients with rheumatoid arthritis who are already at increased risk for major adverse cardiovascular events (MACE), NSAIDs may be safer than opioids, results of a new-user active comparator study suggest.

Among 6,866 patients with RA who started on opioids and 13,698 patients who started on NSAIDs for pain, the use of both weak and strong opioids was associated with a 33% increase in risk for all-cause mortality and a trend toward higher rates of venous thromboembolism (VTE), compared with NSAID use, reported Gulsen Ozen, MD, of the University of Nebraska Medical Center, Omaha.

Neil Osterweil/MDedge News

“Pain in RA is a very complex process, and we know that it’s not solely dependent on the disease activity, but there is no evidence that opioids have any benefit in long-term pain management, and it can even cause hyperalgesia. And as we show, it’s not safer than NSAIDs,” she said in an oral abstract session at the annual meeting of the American College of Rheumatology.

She stressed that patients should be assessed for non-RA causes of pain and should use nonpharmacologic methods when possible.

“If a pharmacological treatment is needed and NSAIDs are contraindicated, the lowest possible dose of weak opioids can be used for a very limited time for acute pain only,” she said.
 

Pain despite disease control

Even when their disease is well controlled, approximately 60% of patients with RA still report pain. NSAIDs are commonly used to treat pain in patients with RA, but they are associated with modest increases in risk for cardiovascular disease (CVD), gastrointestinal bleeding, renal injury, and hypertension.

Some providers are leery of NSAIDs and will instead prescribe either regular or intermittent opioids for pain control in their patients.

Disease-modifying antirheumatic drugs have only minimal pain-relieving benefits, “and even worse, opioids can delay initiation of DMARDs in RA,” Dr. Ozen said.

Opioids have been shown to increase oxidative stress, platelet aggregation, and myocardial fibrosis, as well as hypogonadism, weight gain, and CVD risk factors.

There is little evidence, however, on whether opioids are associated with cardiovascular events in patients with RA. This dearth of data prompted Dr. Ozen and colleagues to study the relative risks for MACE in patients with RA starting on opioids or NSAIDs for pain.

Matched cohorts

They used data from FORWARD, a joint Canadian and U.S. databank for rheumatic diseases, to conduct a new-user active comparator cohort study. The cohort included adults with RA without cancer who participated in FORWARD for a minimum of 1 year between 1998 and 2021.

The patients were followed either from drug initiation until 3 months after the end of treatment, defined as either discontinuation or a switch to a different analgesic, end of study follow-up, or the development of a MACE outcome.

The investigators used propensity score matching to compare each opioid initiator with two NSAID initiators. The participants were matched by age, sex, body mass index, smoking, alcohol, RA duration, disease activity, Health Assessment Questionnaire, visual analog scale for pain, joint surgeries, prior CVD and VTE, hypertension, diabetes, rheumatic diseases comorbidity index, osteoporosis/fractures, thyroid, chronic liver, kidney, lung and mental health diseases, hospitalizations, 36-Item Short Form Health Survey scores, and sleep scores.

The two groups were well matched, except for a slightly higher incidence of VTE in opioid initiators, although incidence rates were low in both groups (0.9% vs. 0.6% of NSAID initiators).
 

Higher death rate in opioid users

The incidence rate of MACE among opioid initiators was 20.6% versus18.9% among NSAID initiators, a difference that was not statistically significant. There were also no significant differences in incidence rates of the individual components of the MACE composite outcome: myocardial infarction, stroke, heart failure, CVD death, or VTE.

There were, however, significantly more deaths from any cause among patients in the opioid group, with an incidence rate of 13.5% versus 10.8% in the NSAID group.

An analysis of the associaion of drug type with outcomes, adjusted for propensity score weight and prior VTE showed that patients on opioids had a statistically significant hazard ratio for death from any cause of 1.33 (95% confidence interval, 1.06-1.67).

The increased risk for all-cause mortality occurred both in patients starting on weak opioids (hydrocodone, tramadol, codeine, pentazocine, and propoxyphene) and on strong opioids (hydromorphone, dihydromorphinone, oxymorphone, butorphanol, methadone, morphine, oxycodone, meperidine, and fentanyl).

As noted before, there was a trend toward an increased risk for VTE among opioid initiators, but this was not statistically significant.

The increase in risk was higher among patients on strong versus weak opioids, suggesting a dose-dependent relationship, Dr. Ozen said.

A comparison of opioid-associated risk for all-cause mortality vs. NSAIDs according to type (nonselective or selective) showed that most of the increase in risk was relative to selective cycloxygenase-2 inhibitors.

‘Beautiful’ analysis

“This is a beautiful piece of analysis on a really difficult question to address because the confounding is really hard to unpick,” commented James Galloway, MBBS, deputy head of the center for rheumatic diseases at King’s College London and consulting rheumatologist at King’s College Hospital, also in London.

“The headline message is that there didn’t appear to be a clear signal that NSAIDs were worse, which is what I thought the preexisting view might have been. And so, people may have paradoxically prescribed opioids in favor of NSAIDs in a person with cardiovascular risk,” he said in an interview. Dr. Galloway attended the oral abstract session but was not involved in the study.

The study was supported by a grant to Dr. Ozen from the Rheumatology Research Foundation. Dr. Galloway reported having no relevant disclosures.

PHILADELPHIA – For patients with rheumatoid arthritis who are already at increased risk for major adverse cardiovascular events (MACE), NSAIDs may be safer than opioids, results of a new-user active comparator study suggest.

Among 6,866 patients with RA who started on opioids and 13,698 patients who started on NSAIDs for pain, the use of both weak and strong opioids was associated with a 33% increase in risk for all-cause mortality and a trend toward higher rates of venous thromboembolism (VTE), compared with NSAID use, reported Gulsen Ozen, MD, of the University of Nebraska Medical Center, Omaha.

Neil Osterweil/MDedge News

“Pain in RA is a very complex process, and we know that it’s not solely dependent on the disease activity, but there is no evidence that opioids have any benefit in long-term pain management, and it can even cause hyperalgesia. And as we show, it’s not safer than NSAIDs,” she said in an oral abstract session at the annual meeting of the American College of Rheumatology.

She stressed that patients should be assessed for non-RA causes of pain and should use nonpharmacologic methods when possible.

“If a pharmacological treatment is needed and NSAIDs are contraindicated, the lowest possible dose of weak opioids can be used for a very limited time for acute pain only,” she said.
 

Pain despite disease control

Even when their disease is well controlled, approximately 60% of patients with RA still report pain. NSAIDs are commonly used to treat pain in patients with RA, but they are associated with modest increases in risk for cardiovascular disease (CVD), gastrointestinal bleeding, renal injury, and hypertension.

Some providers are leery of NSAIDs and will instead prescribe either regular or intermittent opioids for pain control in their patients.

Disease-modifying antirheumatic drugs have only minimal pain-relieving benefits, “and even worse, opioids can delay initiation of DMARDs in RA,” Dr. Ozen said.

Opioids have been shown to increase oxidative stress, platelet aggregation, and myocardial fibrosis, as well as hypogonadism, weight gain, and CVD risk factors.

There is little evidence, however, on whether opioids are associated with cardiovascular events in patients with RA. This dearth of data prompted Dr. Ozen and colleagues to study the relative risks for MACE in patients with RA starting on opioids or NSAIDs for pain.

Matched cohorts

They used data from FORWARD, a joint Canadian and U.S. databank for rheumatic diseases, to conduct a new-user active comparator cohort study. The cohort included adults with RA without cancer who participated in FORWARD for a minimum of 1 year between 1998 and 2021.

The patients were followed either from drug initiation until 3 months after the end of treatment, defined as either discontinuation or a switch to a different analgesic, end of study follow-up, or the development of a MACE outcome.

The investigators used propensity score matching to compare each opioid initiator with two NSAID initiators. The participants were matched by age, sex, body mass index, smoking, alcohol, RA duration, disease activity, Health Assessment Questionnaire, visual analog scale for pain, joint surgeries, prior CVD and VTE, hypertension, diabetes, rheumatic diseases comorbidity index, osteoporosis/fractures, thyroid, chronic liver, kidney, lung and mental health diseases, hospitalizations, 36-Item Short Form Health Survey scores, and sleep scores.

The two groups were well matched, except for a slightly higher incidence of VTE in opioid initiators, although incidence rates were low in both groups (0.9% vs. 0.6% of NSAID initiators).
 

Higher death rate in opioid users

The incidence rate of MACE among opioid initiators was 20.6% versus18.9% among NSAID initiators, a difference that was not statistically significant. There were also no significant differences in incidence rates of the individual components of the MACE composite outcome: myocardial infarction, stroke, heart failure, CVD death, or VTE.

There were, however, significantly more deaths from any cause among patients in the opioid group, with an incidence rate of 13.5% versus 10.8% in the NSAID group.

An analysis of the associaion of drug type with outcomes, adjusted for propensity score weight and prior VTE showed that patients on opioids had a statistically significant hazard ratio for death from any cause of 1.33 (95% confidence interval, 1.06-1.67).

The increased risk for all-cause mortality occurred both in patients starting on weak opioids (hydrocodone, tramadol, codeine, pentazocine, and propoxyphene) and on strong opioids (hydromorphone, dihydromorphinone, oxymorphone, butorphanol, methadone, morphine, oxycodone, meperidine, and fentanyl).

As noted before, there was a trend toward an increased risk for VTE among opioid initiators, but this was not statistically significant.

The increase in risk was higher among patients on strong versus weak opioids, suggesting a dose-dependent relationship, Dr. Ozen said.

A comparison of opioid-associated risk for all-cause mortality vs. NSAIDs according to type (nonselective or selective) showed that most of the increase in risk was relative to selective cycloxygenase-2 inhibitors.

‘Beautiful’ analysis

“This is a beautiful piece of analysis on a really difficult question to address because the confounding is really hard to unpick,” commented James Galloway, MBBS, deputy head of the center for rheumatic diseases at King’s College London and consulting rheumatologist at King’s College Hospital, also in London.

“The headline message is that there didn’t appear to be a clear signal that NSAIDs were worse, which is what I thought the preexisting view might have been. And so, people may have paradoxically prescribed opioids in favor of NSAIDs in a person with cardiovascular risk,” he said in an interview. Dr. Galloway attended the oral abstract session but was not involved in the study.

The study was supported by a grant to Dr. Ozen from the Rheumatology Research Foundation. Dr. Galloway reported having no relevant disclosures.

PHILADELPHIA – Prednisone appears to have the edge over colchicine for control of pain in patients with acute calcium pyrophosphate (CPP) crystal arthritis, an intensely painful rheumatic disease primarily affecting older patients.

Among 111 patients with acute CPP crystal arthritis randomized to receive either prednisone or colchicine for control of acute pain in a multicenter study, 2 days of therapy with the oral agents provided equivalent pain relief on the second day, and patients generally tolerated each agent well, reported Tristan Pascart, MD, from the Groupement Hospitalier de l’Institut Catholique de Lille (France).

Neil Osterweil/MDedge News

“Almost three-fourths of patients are considered to be good responders to both drugs on day 3, and, maybe, safety is the key issue distinguishing the two treatments: Colchicine was generally well tolerated, but even with this very short time frame of treatment, one patient out of five had diarrhea, which is more of a concern in this elderly population at risk of dehydration,” he said in an oral abstract session at the annual meeting of the American College of Rheumatology.

In contrast, only about 6% of patients assigned to prednisone had diarrhea, and other adverse events that occurred more frequently with the corticosteroid, including hypertension, hyperglycemia, and insomnia all resolved after the therapy was stopped.
 

Common and acutely painful

Acute CPP crystal arthritis is a common complication that often occurs during hospitalization for primarily nonrheumatologic causes, Dr. Pascart said, and “in the absence of clinical trials, the management relies on expert opinion, which stems from extrapolated data from gap studies” primarily with prednisone or colchicine, Dr. Pascart said.

To fill in the knowledge gap, Dr. Pascart and colleagues conducted the COLCHICORT study to evaluate whether the two drugs were comparable in efficacy and safety for control of acute pain in a vulnerable population.

The multicenter, open-label trial included patients older than age 65 years with an estimated glomerular filtration rate above 30 mL/min per 1.73 m² who presented with acute CPP deposition arthritis with symptoms occurring within the previous 36 hours. CPP arthritis was defined by the identification of CPP crystals on synovial fluid analysis or typical clinical presentation with evidence of chondrocalcinosis on x-rays or ultrasound.

Patients with a history of gout, cognitive decline that could impair pain assessment, or contraindications to either of the study drugs were excluded.

The participants were randomized to receive either colchicine 1.5 mg (1 mg to start, then 0.5 mg one hour later) at baseline and then 1 mg on day 1, or oral prednisone 30 mg at baseline and on day 1. The patients also received 1 g of systemic acetaminophen, and three 50-mg doses of tramadol during the first 24 hours.

Of the 111 patients randomized, 54 were assigned to receive prednisone, and 57 were assigned to receive colchicine. Baseline characteristics were similar between the groups, with a mean age of about 86 years, body mass index of around 25 kg/m², and blood pressure in the range of 130/69 mm Hg.

For nearly half of all patients in study each arm the most painful joint was the knee, followed by wrists and ankles.

There was no difference between the groups in the primary efficacy outcome of a change at 24 hours over baseline in visual analog scale (VAS) (0-100 mm) scores, either in a per-protocol analysis or modified intention-to-treat analysis. The mean change in VAS at 24 hours in the colchicine group was –36.6 mm, compared with –37.7 mm in the prednisone group. The investigators had previously determined that any difference between the two drugs of less than 13 mm on pain VAS at 24 hours would meet the definition for equivalent efficacy.

In both groups, a majority of patients had either an improvement greater than 50% in pain VAS scores and/or a pain VAS score less than 40 mm at both 24 and 48 hours.

At 7 days of follow-up, 21.8% of patients assigned to colchicine had diarrhea, compared with 5.6% of those assigned to prednisone. Adverse events occurring more frequently with prednisone included hyperglycemia, hypertension, and insomnia.

Patients who received colchicine and were also on statins had a trend toward a higher risk for diarrhea, but the study was not adequately powered to detect an association, and the trend was not statistically significant, Dr. Pascart said.

“Taken together, safety issues suggest that prednisone should be considered as the first-line therapy in acute CPP crystal arthritis. Future research is warranted to determine factors increasing the risk of colchicine-induced diarrhea,” he concluded.
 

Both drugs are used

Sara K. Tedeschi, MD, from Brigham & Women’s Hospital in Boston, who attended the session where the data were presented, has a special clinical interest in CPP deposition disease. She applauded Dr. Pascart and colleagues for conducting a rare clinical trial in CPP crystal arthritis.

In an interview, she said that the study suggests “we can keep in mind shorter courses of treatment for acute CPP crystal arthritis; I think that’s one big takeaway from this study.”

Asked whether she would change her practice based on the findings, Dr. Tedeschi replied: “I personally am not sure that I would be moved to use prednisone more than colchicine; I actually take away from this that colchicine is equivalent to prednisone for short-term use for CPP arthritis, but I think it’s also really important to note that this is in the context of quite a lot of acetaminophen and quite a lot of tramadol, and frankly I don’t usually use tramadol with my patients, but I might consider doing that, especially as there were no delirium events in this population.”

Dr. Tedeschi was not involved in the study.

Asked the same question, Michael Toprover, MD, from New York University Langone Medical Center, a moderator of the session who was not involved in the study, said: “I usually use a combination of medications. I generally, in someone who is hospitalized in particular and is in such severe pain, use a combination of colchicine and prednisone, unless I’m worried about infection, in which case I’ll start colchicine until we’ve proven that it’s CPPD, and then I’ll add prednisone.”

The study was funded by PHRC-1 GIRCI Nord Ouest, a clinical research program funded by the Ministry of Health in France. Dr. Pascart, Dr. Tedeschi, and Dr. Toprover all reported having no relevant conflicts of interest.

PHILADELPHIA – Prednisone appears to have the edge over colchicine for control of pain in patients with acute calcium pyrophosphate (CPP) crystal arthritis, an intensely painful rheumatic disease primarily affecting older patients.

Among 111 patients with acute CPP crystal arthritis randomized to receive either prednisone or colchicine for control of acute pain in a multicenter study, 2 days of therapy with the oral agents provided equivalent pain relief on the second day, and patients generally tolerated each agent well, reported Tristan Pascart, MD, from the Groupement Hospitalier de l’Institut Catholique de Lille (France).

Neil Osterweil/MDedge News

“Almost three-fourths of patients are considered to be good responders to both drugs on day 3, and, maybe, safety is the key issue distinguishing the two treatments: Colchicine was generally well tolerated, but even with this very short time frame of treatment, one patient out of five had diarrhea, which is more of a concern in this elderly population at risk of dehydration,” he said in an oral abstract session at the annual meeting of the American College of Rheumatology.

In contrast, only about 6% of patients assigned to prednisone had diarrhea, and other adverse events that occurred more frequently with the corticosteroid, including hypertension, hyperglycemia, and insomnia all resolved after the therapy was stopped.
 

Common and acutely painful

Acute CPP crystal arthritis is a common complication that often occurs during hospitalization for primarily nonrheumatologic causes, Dr. Pascart said, and “in the absence of clinical trials, the management relies on expert opinion, which stems from extrapolated data from gap studies” primarily with prednisone or colchicine, Dr. Pascart said.

To fill in the knowledge gap, Dr. Pascart and colleagues conducted the COLCHICORT study to evaluate whether the two drugs were comparable in efficacy and safety for control of acute pain in a vulnerable population.

The multicenter, open-label trial included patients older than age 65 years with an estimated glomerular filtration rate above 30 mL/min per 1.73 m² who presented with acute CPP deposition arthritis with symptoms occurring within the previous 36 hours. CPP arthritis was defined by the identification of CPP crystals on synovial fluid analysis or typical clinical presentation with evidence of chondrocalcinosis on x-rays or ultrasound.

Patients with a history of gout, cognitive decline that could impair pain assessment, or contraindications to either of the study drugs were excluded.

The participants were randomized to receive either colchicine 1.5 mg (1 mg to start, then 0.5 mg one hour later) at baseline and then 1 mg on day 1, or oral prednisone 30 mg at baseline and on day 1. The patients also received 1 g of systemic acetaminophen, and three 50-mg doses of tramadol during the first 24 hours.

Of the 111 patients randomized, 54 were assigned to receive prednisone, and 57 were assigned to receive colchicine. Baseline characteristics were similar between the groups, with a mean age of about 86 years, body mass index of around 25 kg/m², and blood pressure in the range of 130/69 mm Hg.

For nearly half of all patients in study each arm the most painful joint was the knee, followed by wrists and ankles.

There was no difference between the groups in the primary efficacy outcome of a change at 24 hours over baseline in visual analog scale (VAS) (0-100 mm) scores, either in a per-protocol analysis or modified intention-to-treat analysis. The mean change in VAS at 24 hours in the colchicine group was –36.6 mm, compared with –37.7 mm in the prednisone group. The investigators had previously determined that any difference between the two drugs of less than 13 mm on pain VAS at 24 hours would meet the definition for equivalent efficacy.

In both groups, a majority of patients had either an improvement greater than 50% in pain VAS scores and/or a pain VAS score less than 40 mm at both 24 and 48 hours.

At 7 days of follow-up, 21.8% of patients assigned to colchicine had diarrhea, compared with 5.6% of those assigned to prednisone. Adverse events occurring more frequently with prednisone included hyperglycemia, hypertension, and insomnia.

Patients who received colchicine and were also on statins had a trend toward a higher risk for diarrhea, but the study was not adequately powered to detect an association, and the trend was not statistically significant, Dr. Pascart said.

“Taken together, safety issues suggest that prednisone should be considered as the first-line therapy in acute CPP crystal arthritis. Future research is warranted to determine factors increasing the risk of colchicine-induced diarrhea,” he concluded.
 

Both drugs are used

Sara K. Tedeschi, MD, from Brigham & Women’s Hospital in Boston, who attended the session where the data were presented, has a special clinical interest in CPP deposition disease. She applauded Dr. Pascart and colleagues for conducting a rare clinical trial in CPP crystal arthritis.

In an interview, she said that the study suggests “we can keep in mind shorter courses of treatment for acute CPP crystal arthritis; I think that’s one big takeaway from this study.”

Asked whether she would change her practice based on the findings, Dr. Tedeschi replied: “I personally am not sure that I would be moved to use prednisone more than colchicine; I actually take away from this that colchicine is equivalent to prednisone for short-term use for CPP arthritis, but I think it’s also really important to note that this is in the context of quite a lot of acetaminophen and quite a lot of tramadol, and frankly I don’t usually use tramadol with my patients, but I might consider doing that, especially as there were no delirium events in this population.”

Dr. Tedeschi was not involved in the study.

Asked the same question, Michael Toprover, MD, from New York University Langone Medical Center, a moderator of the session who was not involved in the study, said: “I usually use a combination of medications. I generally, in someone who is hospitalized in particular and is in such severe pain, use a combination of colchicine and prednisone, unless I’m worried about infection, in which case I’ll start colchicine until we’ve proven that it’s CPPD, and then I’ll add prednisone.”

The study was funded by PHRC-1 GIRCI Nord Ouest, a clinical research program funded by the Ministry of Health in France. Dr. Pascart, Dr. Tedeschi, and Dr. Toprover all reported having no relevant conflicts of interest.

PHILADELPHIA – Prednisone appears to have the edge over colchicine for control of pain in patients with acute calcium pyrophosphate (CPP) crystal arthritis, an intensely painful rheumatic disease primarily affecting older patients.

Among 111 patients with acute CPP crystal arthritis randomized to receive either prednisone or colchicine for control of acute pain in a multicenter study, 2 days of therapy with the oral agents provided equivalent pain relief on the second day, and patients generally tolerated each agent well, reported Tristan Pascart, MD, from the Groupement Hospitalier de l’Institut Catholique de Lille (France).

Neil Osterweil/MDedge News

“Almost three-fourths of patients are considered to be good responders to both drugs on day 3, and, maybe, safety is the key issue distinguishing the two treatments: Colchicine was generally well tolerated, but even with this very short time frame of treatment, one patient out of five had diarrhea, which is more of a concern in this elderly population at risk of dehydration,” he said in an oral abstract session at the annual meeting of the American College of Rheumatology.

In contrast, only about 6% of patients assigned to prednisone had diarrhea, and other adverse events that occurred more frequently with the corticosteroid, including hypertension, hyperglycemia, and insomnia all resolved after the therapy was stopped.
 

Common and acutely painful

Acute CPP crystal arthritis is a common complication that often occurs during hospitalization for primarily nonrheumatologic causes, Dr. Pascart said, and “in the absence of clinical trials, the management relies on expert opinion, which stems from extrapolated data from gap studies” primarily with prednisone or colchicine, Dr. Pascart said.

To fill in the knowledge gap, Dr. Pascart and colleagues conducted the COLCHICORT study to evaluate whether the two drugs were comparable in efficacy and safety for control of acute pain in a vulnerable population.

The multicenter, open-label trial included patients older than age 65 years with an estimated glomerular filtration rate above 30 mL/min per 1.73 m² who presented with acute CPP deposition arthritis with symptoms occurring within the previous 36 hours. CPP arthritis was defined by the identification of CPP crystals on synovial fluid analysis or typical clinical presentation with evidence of chondrocalcinosis on x-rays or ultrasound.

Patients with a history of gout, cognitive decline that could impair pain assessment, or contraindications to either of the study drugs were excluded.

The participants were randomized to receive either colchicine 1.5 mg (1 mg to start, then 0.5 mg one hour later) at baseline and then 1 mg on day 1, or oral prednisone 30 mg at baseline and on day 1. The patients also received 1 g of systemic acetaminophen, and three 50-mg doses of tramadol during the first 24 hours.

Of the 111 patients randomized, 54 were assigned to receive prednisone, and 57 were assigned to receive colchicine. Baseline characteristics were similar between the groups, with a mean age of about 86 years, body mass index of around 25 kg/m², and blood pressure in the range of 130/69 mm Hg.

For nearly half of all patients in study each arm the most painful joint was the knee, followed by wrists and ankles.

There was no difference between the groups in the primary efficacy outcome of a change at 24 hours over baseline in visual analog scale (VAS) (0-100 mm) scores, either in a per-protocol analysis or modified intention-to-treat analysis. The mean change in VAS at 24 hours in the colchicine group was –36.6 mm, compared with –37.7 mm in the prednisone group. The investigators had previously determined that any difference between the two drugs of less than 13 mm on pain VAS at 24 hours would meet the definition for equivalent efficacy.

In both groups, a majority of patients had either an improvement greater than 50% in pain VAS scores and/or a pain VAS score less than 40 mm at both 24 and 48 hours.

At 7 days of follow-up, 21.8% of patients assigned to colchicine had diarrhea, compared with 5.6% of those assigned to prednisone. Adverse events occurring more frequently with prednisone included hyperglycemia, hypertension, and insomnia.

Patients who received colchicine and were also on statins had a trend toward a higher risk for diarrhea, but the study was not adequately powered to detect an association, and the trend was not statistically significant, Dr. Pascart said.

“Taken together, safety issues suggest that prednisone should be considered as the first-line therapy in acute CPP crystal arthritis. Future research is warranted to determine factors increasing the risk of colchicine-induced diarrhea,” he concluded.
 

Both drugs are used

Sara K. Tedeschi, MD, from Brigham & Women’s Hospital in Boston, who attended the session where the data were presented, has a special clinical interest in CPP deposition disease. She applauded Dr. Pascart and colleagues for conducting a rare clinical trial in CPP crystal arthritis.

In an interview, she said that the study suggests “we can keep in mind shorter courses of treatment for acute CPP crystal arthritis; I think that’s one big takeaway from this study.”

Asked whether she would change her practice based on the findings, Dr. Tedeschi replied: “I personally am not sure that I would be moved to use prednisone more than colchicine; I actually take away from this that colchicine is equivalent to prednisone for short-term use for CPP arthritis, but I think it’s also really important to note that this is in the context of quite a lot of acetaminophen and quite a lot of tramadol, and frankly I don’t usually use tramadol with my patients, but I might consider doing that, especially as there were no delirium events in this population.”

Dr. Tedeschi was not involved in the study.

Asked the same question, Michael Toprover, MD, from New York University Langone Medical Center, a moderator of the session who was not involved in the study, said: “I usually use a combination of medications. I generally, in someone who is hospitalized in particular and is in such severe pain, use a combination of colchicine and prednisone, unless I’m worried about infection, in which case I’ll start colchicine until we’ve proven that it’s CPPD, and then I’ll add prednisone.”

The study was funded by PHRC-1 GIRCI Nord Ouest, a clinical research program funded by the Ministry of Health in France. Dr. Pascart, Dr. Tedeschi, and Dr. Toprover all reported having no relevant conflicts of interest.

PHILADELPHIA – Women with spondyloarthritis (SpA) who are desiring pregnancy may want to consider decreasing use or discontinuing use (with supervision) of nonsteroidal anti-inflammatory drugs before conception, new data suggest.

Researchers have found a connection between NSAID use and age and a significantly longer time to conception among women with spondyloarthritis. Sabrina Hamroun, MMed, with the rheumatology department at the University Hospital Cochin, Paris, presented the findings during a press conference at the annual meeting of the American College of Rheumatology.

Subfertility group took an average of 16 months to get pregnant

Subfertility was observed in 40 (45.4%) of the women, with an average time to conception of 16.1 months. A woman was considered subfertile if her time to conception was more than 12 months or if she did not become pregnant.

The average preconception Bath Ankylosing Spondylitis Disease Activity Index score was 2.9 (+/- 2.1), the authors noted. The average age of the participants was 32 years.

Twenty-three patients were treated with NSAIDs, eight with corticosteroids, 12 with conventional synthetic disease-modifying antirheumatic drugs, and 61 with biologics.

Researchers adjusted for factors including age, body mass index, disease duration and severity, smoking, form of SpA (axial, peripheral, or both), and medication in the preconception period.

They found significant associations between longer time to conception and age (hazard ratio, 1.22; 95% confidence interval, 1.08-1.40; P < .001), and a much higher hazard ratio with the use of NSAIDs during preconception (HR, 3.01; 95% CI, 2.15-3.85; P = .01).

Some data unavailable

Ms. Hamroun acknowledged that no data were available on the frequency of sexual intercourse or quality of life, factors that could affect time to conception. Women were asked when they discontinued contraceptive use and actively began trying to become pregnant.

She stated that information on the dose of NSAIDs used by the patients was incomplete, noting, “We were therefore unable to adjust the results of our statistical analyses on the dose used by patients.”

Additionally, because the study participants were patients at tertiary centers in France and had more severe disease, the results may not be generalizable to all women of childbearing age. Patients with less severe SpA are often managed in outpatient settings in France, she said.

When asked about alternatives to NSAIDs, Ms. Hamroun said that anti–tumor necrosis factor agents with low placental passage may be a good alternative “if a woman with long-standing difficulties to conceive needs a regular use of NSAIDs to control disease activity, in the absence of any other cause of subfertility.”

The patient’s age must also be considered, she noted.

“A therapeutic switch may be favored in a woman over 35 years of age, for example, whose fertility is already impaired by age,” Ms. Hamroun said.

As for the mechanism that might explain the effects of NSAIDs on conception, Ms. Hamroun said that prostaglandins are essential to ovulation and embryo implantation and explained that NSAIDs may work against ovulation and result in poor implantation (miscarriage) by blocking prostaglandins.

She pointed out that her results are in line with the ACR’s recommendation to discontinue NSAID use during the preconception period in women with SpA who are having difficulty conceiving.
 

Control before conception is important

Sinead Maguire, MD, a clinical and research fellow in the Spondylitis Program at Toronto (Ont.) Western Hospital who was not part of the study, said the study highlights the importance of optimizing disease control before conception.

“There are a number of things rheumatologists can do to support our SpA patients when they are trying to conceive,” she told this news organization. “One of the most important issues to address is ensuring their SpA is in remission and continues to remain so. For that reason, if a woman is requiring regular NSAIDs for symptom control, the results of this study might encourage me to consider a biologic agent sooner to ensure remission.”

She urged women who want to become pregnant to discuss medications with their rheumatologist before trying to conceive.

“It is very exciting to see studies such as this so that rheumatologists can provide answers to our patients’ questions with evidence-based advice,” she said.

Ms. Hamroun and several coauthors had no disclosures. Other coauthors disclosed relationships with companies including Merck/MSD, Novartis, Janssen, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Galapagos, Eli Lilly, Novartis, and/or UCB. Dr. Maguire reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Women with spondyloarthritis (SpA) who are desiring pregnancy may want to consider decreasing use or discontinuing use (with supervision) of nonsteroidal anti-inflammatory drugs before conception, new data suggest.

Researchers have found a connection between NSAID use and age and a significantly longer time to conception among women with spondyloarthritis. Sabrina Hamroun, MMed, with the rheumatology department at the University Hospital Cochin, Paris, presented the findings during a press conference at the annual meeting of the American College of Rheumatology.

Subfertility group took an average of 16 months to get pregnant

Subfertility was observed in 40 (45.4%) of the women, with an average time to conception of 16.1 months. A woman was considered subfertile if her time to conception was more than 12 months or if she did not become pregnant.

The average preconception Bath Ankylosing Spondylitis Disease Activity Index score was 2.9 (+/- 2.1), the authors noted. The average age of the participants was 32 years.

Twenty-three patients were treated with NSAIDs, eight with corticosteroids, 12 with conventional synthetic disease-modifying antirheumatic drugs, and 61 with biologics.

Researchers adjusted for factors including age, body mass index, disease duration and severity, smoking, form of SpA (axial, peripheral, or both), and medication in the preconception period.

They found significant associations between longer time to conception and age (hazard ratio, 1.22; 95% confidence interval, 1.08-1.40; P < .001), and a much higher hazard ratio with the use of NSAIDs during preconception (HR, 3.01; 95% CI, 2.15-3.85; P = .01).

Some data unavailable

Ms. Hamroun acknowledged that no data were available on the frequency of sexual intercourse or quality of life, factors that could affect time to conception. Women were asked when they discontinued contraceptive use and actively began trying to become pregnant.

She stated that information on the dose of NSAIDs used by the patients was incomplete, noting, “We were therefore unable to adjust the results of our statistical analyses on the dose used by patients.”

Additionally, because the study participants were patients at tertiary centers in France and had more severe disease, the results may not be generalizable to all women of childbearing age. Patients with less severe SpA are often managed in outpatient settings in France, she said.

When asked about alternatives to NSAIDs, Ms. Hamroun said that anti–tumor necrosis factor agents with low placental passage may be a good alternative “if a woman with long-standing difficulties to conceive needs a regular use of NSAIDs to control disease activity, in the absence of any other cause of subfertility.”

The patient’s age must also be considered, she noted.

“A therapeutic switch may be favored in a woman over 35 years of age, for example, whose fertility is already impaired by age,” Ms. Hamroun said.

As for the mechanism that might explain the effects of NSAIDs on conception, Ms. Hamroun said that prostaglandins are essential to ovulation and embryo implantation and explained that NSAIDs may work against ovulation and result in poor implantation (miscarriage) by blocking prostaglandins.

She pointed out that her results are in line with the ACR’s recommendation to discontinue NSAID use during the preconception period in women with SpA who are having difficulty conceiving.
 

Control before conception is important

Sinead Maguire, MD, a clinical and research fellow in the Spondylitis Program at Toronto (Ont.) Western Hospital who was not part of the study, said the study highlights the importance of optimizing disease control before conception.

“There are a number of things rheumatologists can do to support our SpA patients when they are trying to conceive,” she told this news organization. “One of the most important issues to address is ensuring their SpA is in remission and continues to remain so. For that reason, if a woman is requiring regular NSAIDs for symptom control, the results of this study might encourage me to consider a biologic agent sooner to ensure remission.”

She urged women who want to become pregnant to discuss medications with their rheumatologist before trying to conceive.

“It is very exciting to see studies such as this so that rheumatologists can provide answers to our patients’ questions with evidence-based advice,” she said.

Ms. Hamroun and several coauthors had no disclosures. Other coauthors disclosed relationships with companies including Merck/MSD, Novartis, Janssen, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Galapagos, Eli Lilly, Novartis, and/or UCB. Dr. Maguire reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Women with spondyloarthritis (SpA) who are desiring pregnancy may want to consider decreasing use or discontinuing use (with supervision) of nonsteroidal anti-inflammatory drugs before conception, new data suggest.

Researchers have found a connection between NSAID use and age and a significantly longer time to conception among women with spondyloarthritis. Sabrina Hamroun, MMed, with the rheumatology department at the University Hospital Cochin, Paris, presented the findings during a press conference at the annual meeting of the American College of Rheumatology.

Subfertility group took an average of 16 months to get pregnant

Subfertility was observed in 40 (45.4%) of the women, with an average time to conception of 16.1 months. A woman was considered subfertile if her time to conception was more than 12 months or if she did not become pregnant.

The average preconception Bath Ankylosing Spondylitis Disease Activity Index score was 2.9 (+/- 2.1), the authors noted. The average age of the participants was 32 years.

Twenty-three patients were treated with NSAIDs, eight with corticosteroids, 12 with conventional synthetic disease-modifying antirheumatic drugs, and 61 with biologics.

Researchers adjusted for factors including age, body mass index, disease duration and severity, smoking, form of SpA (axial, peripheral, or both), and medication in the preconception period.

They found significant associations between longer time to conception and age (hazard ratio, 1.22; 95% confidence interval, 1.08-1.40; P < .001), and a much higher hazard ratio with the use of NSAIDs during preconception (HR, 3.01; 95% CI, 2.15-3.85; P = .01).

Some data unavailable

Ms. Hamroun acknowledged that no data were available on the frequency of sexual intercourse or quality of life, factors that could affect time to conception. Women were asked when they discontinued contraceptive use and actively began trying to become pregnant.

She stated that information on the dose of NSAIDs used by the patients was incomplete, noting, “We were therefore unable to adjust the results of our statistical analyses on the dose used by patients.”

Additionally, because the study participants were patients at tertiary centers in France and had more severe disease, the results may not be generalizable to all women of childbearing age. Patients with less severe SpA are often managed in outpatient settings in France, she said.

When asked about alternatives to NSAIDs, Ms. Hamroun said that anti–tumor necrosis factor agents with low placental passage may be a good alternative “if a woman with long-standing difficulties to conceive needs a regular use of NSAIDs to control disease activity, in the absence of any other cause of subfertility.”

The patient’s age must also be considered, she noted.

“A therapeutic switch may be favored in a woman over 35 years of age, for example, whose fertility is already impaired by age,” Ms. Hamroun said.

As for the mechanism that might explain the effects of NSAIDs on conception, Ms. Hamroun said that prostaglandins are essential to ovulation and embryo implantation and explained that NSAIDs may work against ovulation and result in poor implantation (miscarriage) by blocking prostaglandins.

She pointed out that her results are in line with the ACR’s recommendation to discontinue NSAID use during the preconception period in women with SpA who are having difficulty conceiving.
 

Control before conception is important

Sinead Maguire, MD, a clinical and research fellow in the Spondylitis Program at Toronto (Ont.) Western Hospital who was not part of the study, said the study highlights the importance of optimizing disease control before conception.

“There are a number of things rheumatologists can do to support our SpA patients when they are trying to conceive,” she told this news organization. “One of the most important issues to address is ensuring their SpA is in remission and continues to remain so. For that reason, if a woman is requiring regular NSAIDs for symptom control, the results of this study might encourage me to consider a biologic agent sooner to ensure remission.”

She urged women who want to become pregnant to discuss medications with their rheumatologist before trying to conceive.

“It is very exciting to see studies such as this so that rheumatologists can provide answers to our patients’ questions with evidence-based advice,” she said.

Ms. Hamroun and several coauthors had no disclosures. Other coauthors disclosed relationships with companies including Merck/MSD, Novartis, Janssen, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Galapagos, Eli Lilly, Novartis, and/or UCB. Dr. Maguire reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Combining the immunomodulatory agent mycophenolate with the antifibrotic pirfenidone led to more rapid improvement and showed a trend to be more effective than mycophenolate mofetil alone for treating the signs and symptoms of scleroderma-related interstitial lung disease, but the combination therapy came with an increase in side effects, according to results from the Scleroderma Lung Study III.

Dinesh Khanna, MBBS, MSc, of the University of Michigan, Ann Arbor, presented the results at the annual meeting of the American College of Rheumatology. He noted some problems with the study – namely its small size, enrolling only 51 patients, about one-third of its original goal. But he also said it showed a potential signal for efficacy and that the study itself could serve as a “template” for future studies of combination mycophenolate mofetil (MMF) plus pirfenidone therapy for scleroderma-related interstitial lung disease (SSc-ILD).

“The pirfenidone patients had quite a bit more GI side effects and photosensitivity, and those are known side effects,” Dr. Khanna said in an interview. “So the combination therapy had more side effects but trends to higher efficacy.”

The design of SLS-III, a phase 2 clinical trial, was a challenge, Dr. Khanna explained. The goal was to enroll 150 SSc-ILD patients who hadn’t had any previous treatment for their disease. Finding those patients proved difficult. “In fact, if you look at the recent history, 70% of the patients with early diffuse scleroderma are on MMF,” he said in his presentation. Compounding low study enrollment was the intervening COVID-19 pandemic, he added.
 

Testing a faster-acting combination

Nonetheless, the trial managed to enroll 27 patients in the combination therapy group and 24 in the MMF-plus-placebo group and compared their outcomes over 18 months. Study dosing was 1,500 mg MMF twice daily and pirfenidone 801 mg three times daily, titrated to the tolerable dose.

Despite the study’s being underpowered, Dr. Khanna said, it still reported some notable outcomes that merit further investigation. “I think what was intriguing in the study was the long-term benefit in the patient-reported outcomes and the structural changes,” he said in the interview.

Among those notable outcomes was a clinically significant change in forced vital capacity (FVC) percentage for the combination vs. the placebo groups: 2.24% vs. 2.09%. He also noted that the combination group saw a somewhat more robust improvement in FVC at six months: 2.59% (± 0.98%) vs. 0.92% (± 1.1%) in the placebo group.

The combination group showed greater improvements in high-resolution computed tomography-evaluated lung involvement and lung fibrosis and patient-reported outcomes, including a statistically significant 3.67-point greater improvement in PROMIS-29 physical function score (4.42 vs. 0.75).

The patients on combination therapy had higher rates of serious adverse events (SAEs), and seven discontinued one or both study drugs early, all in the combined arm. Four combination therapy patients had six SAEs, compared to two placebo patients with three SAEs. In the combination group, SAEs included chest pain, herpes zoster ophthalmicus, nodular basal cell cancer, marginal zone B cell lymphoma, renal crisis, and dyspnea. SAEs in the placebo group were colitis, COVID-19 and hypoxic respiratory failure.

Study design challenges

Nonetheless, Dr. Khanna said the SLS-III data are consistent with the SLS-II findings, with mean improvements in FVC of 2.24% and 2.1%, respectively.

“The next study may be able to replicate what we tried to do, keeping in mind that there are really no MMF-naive patients who are walking around,” Dr. Khanna said. “So the challenge is about the feasibility of recruiting within a trial vs. trying to show a statistical difference between the drug and placebo.”

This study could serve as a foundation for future studies of MMF in patients with SSc-ILD, Robert Spiera, MD, of the Hospital for Special Surgery in New York, said in an interview. “There are lessons to be learned both from the study but also from prior studies looking at MMF use in the background in patients treated with other drugs in clinical trials,” he said.

Dr. Spiera noted that the study had other challenges besides the difficulty in recruiting patients who hadn’t been on MMF therapy. “A great challenge is that the benefit with regard to the impact on the lungs from MMF seems most prominent in the first 6 months to a year to even 2 years that somebody is on the drug,” he said.

The other challenge with this study is that a large proportion of patients had limited systemic disease and relatively lower levels of skin disease compared with other studies of patients on MMF, Dr. Spiera said.

“The optimal treatment of scleroderma-associated lung disease remains a very important and not-adequately met need,” he said. “Particularly, we’re looking for drugs that are tolerable in a patient population that are very prone to GI side effects in general. This study and others have taught us a lot about trial design, and I think more globally this will allow us to move this field forward.”

Dr. Khanna disclosed relationships with Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Horizon Therapeutics USA, Janssen Global Services, Prometheus Biosciences, Mitsubishi Tanabe Pharma Corp., Genentech/Roche, Theraly, and Pfizer. Genentech provided funding for the study and pirfenidone and placebo drugs at no cost.

Dr. Spiera disclosed relationships with GlaxoSmithKline, Boehringer-Ingelheim, Corbus Pharmaceutical, InflaRx, AbbVie/Abbott, Sanofi, Novartis, Chemocentryx, Roche and Vera.

PHILADELPHIA – Combining the immunomodulatory agent mycophenolate with the antifibrotic pirfenidone led to more rapid improvement and showed a trend to be more effective than mycophenolate mofetil alone for treating the signs and symptoms of scleroderma-related interstitial lung disease, but the combination therapy came with an increase in side effects, according to results from the Scleroderma Lung Study III.

Dinesh Khanna, MBBS, MSc, of the University of Michigan, Ann Arbor, presented the results at the annual meeting of the American College of Rheumatology. He noted some problems with the study – namely its small size, enrolling only 51 patients, about one-third of its original goal. But he also said it showed a potential signal for efficacy and that the study itself could serve as a “template” for future studies of combination mycophenolate mofetil (MMF) plus pirfenidone therapy for scleroderma-related interstitial lung disease (SSc-ILD).

“The pirfenidone patients had quite a bit more GI side effects and photosensitivity, and those are known side effects,” Dr. Khanna said in an interview. “So the combination therapy had more side effects but trends to higher efficacy.”

The design of SLS-III, a phase 2 clinical trial, was a challenge, Dr. Khanna explained. The goal was to enroll 150 SSc-ILD patients who hadn’t had any previous treatment for their disease. Finding those patients proved difficult. “In fact, if you look at the recent history, 70% of the patients with early diffuse scleroderma are on MMF,” he said in his presentation. Compounding low study enrollment was the intervening COVID-19 pandemic, he added.
 

Testing a faster-acting combination

Nonetheless, the trial managed to enroll 27 patients in the combination therapy group and 24 in the MMF-plus-placebo group and compared their outcomes over 18 months. Study dosing was 1,500 mg MMF twice daily and pirfenidone 801 mg three times daily, titrated to the tolerable dose.

Despite the study’s being underpowered, Dr. Khanna said, it still reported some notable outcomes that merit further investigation. “I think what was intriguing in the study was the long-term benefit in the patient-reported outcomes and the structural changes,” he said in the interview.

Among those notable outcomes was a clinically significant change in forced vital capacity (FVC) percentage for the combination vs. the placebo groups: 2.24% vs. 2.09%. He also noted that the combination group saw a somewhat more robust improvement in FVC at six months: 2.59% (± 0.98%) vs. 0.92% (± 1.1%) in the placebo group.

The combination group showed greater improvements in high-resolution computed tomography-evaluated lung involvement and lung fibrosis and patient-reported outcomes, including a statistically significant 3.67-point greater improvement in PROMIS-29 physical function score (4.42 vs. 0.75).

The patients on combination therapy had higher rates of serious adverse events (SAEs), and seven discontinued one or both study drugs early, all in the combined arm. Four combination therapy patients had six SAEs, compared to two placebo patients with three SAEs. In the combination group, SAEs included chest pain, herpes zoster ophthalmicus, nodular basal cell cancer, marginal zone B cell lymphoma, renal crisis, and dyspnea. SAEs in the placebo group were colitis, COVID-19 and hypoxic respiratory failure.

Study design challenges

Nonetheless, Dr. Khanna said the SLS-III data are consistent with the SLS-II findings, with mean improvements in FVC of 2.24% and 2.1%, respectively.

“The next study may be able to replicate what we tried to do, keeping in mind that there are really no MMF-naive patients who are walking around,” Dr. Khanna said. “So the challenge is about the feasibility of recruiting within a trial vs. trying to show a statistical difference between the drug and placebo.”

This study could serve as a foundation for future studies of MMF in patients with SSc-ILD, Robert Spiera, MD, of the Hospital for Special Surgery in New York, said in an interview. “There are lessons to be learned both from the study but also from prior studies looking at MMF use in the background in patients treated with other drugs in clinical trials,” he said.

Dr. Spiera noted that the study had other challenges besides the difficulty in recruiting patients who hadn’t been on MMF therapy. “A great challenge is that the benefit with regard to the impact on the lungs from MMF seems most prominent in the first 6 months to a year to even 2 years that somebody is on the drug,” he said.

The other challenge with this study is that a large proportion of patients had limited systemic disease and relatively lower levels of skin disease compared with other studies of patients on MMF, Dr. Spiera said.

“The optimal treatment of scleroderma-associated lung disease remains a very important and not-adequately met need,” he said. “Particularly, we’re looking for drugs that are tolerable in a patient population that are very prone to GI side effects in general. This study and others have taught us a lot about trial design, and I think more globally this will allow us to move this field forward.”

Dr. Khanna disclosed relationships with Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Horizon Therapeutics USA, Janssen Global Services, Prometheus Biosciences, Mitsubishi Tanabe Pharma Corp., Genentech/Roche, Theraly, and Pfizer. Genentech provided funding for the study and pirfenidone and placebo drugs at no cost.

Dr. Spiera disclosed relationships with GlaxoSmithKline, Boehringer-Ingelheim, Corbus Pharmaceutical, InflaRx, AbbVie/Abbott, Sanofi, Novartis, Chemocentryx, Roche and Vera.

PHILADELPHIA – Combining the immunomodulatory agent mycophenolate with the antifibrotic pirfenidone led to more rapid improvement and showed a trend to be more effective than mycophenolate mofetil alone for treating the signs and symptoms of scleroderma-related interstitial lung disease, but the combination therapy came with an increase in side effects, according to results from the Scleroderma Lung Study III.

Dinesh Khanna, MBBS, MSc, of the University of Michigan, Ann Arbor, presented the results at the annual meeting of the American College of Rheumatology. He noted some problems with the study – namely its small size, enrolling only 51 patients, about one-third of its original goal. But he also said it showed a potential signal for efficacy and that the study itself could serve as a “template” for future studies of combination mycophenolate mofetil (MMF) plus pirfenidone therapy for scleroderma-related interstitial lung disease (SSc-ILD).

“The pirfenidone patients had quite a bit more GI side effects and photosensitivity, and those are known side effects,” Dr. Khanna said in an interview. “So the combination therapy had more side effects but trends to higher efficacy.”

The design of SLS-III, a phase 2 clinical trial, was a challenge, Dr. Khanna explained. The goal was to enroll 150 SSc-ILD patients who hadn’t had any previous treatment for their disease. Finding those patients proved difficult. “In fact, if you look at the recent history, 70% of the patients with early diffuse scleroderma are on MMF,” he said in his presentation. Compounding low study enrollment was the intervening COVID-19 pandemic, he added.
 

Testing a faster-acting combination

Nonetheless, the trial managed to enroll 27 patients in the combination therapy group and 24 in the MMF-plus-placebo group and compared their outcomes over 18 months. Study dosing was 1,500 mg MMF twice daily and pirfenidone 801 mg three times daily, titrated to the tolerable dose.

Despite the study’s being underpowered, Dr. Khanna said, it still reported some notable outcomes that merit further investigation. “I think what was intriguing in the study was the long-term benefit in the patient-reported outcomes and the structural changes,” he said in the interview.

Among those notable outcomes was a clinically significant change in forced vital capacity (FVC) percentage for the combination vs. the placebo groups: 2.24% vs. 2.09%. He also noted that the combination group saw a somewhat more robust improvement in FVC at six months: 2.59% (± 0.98%) vs. 0.92% (± 1.1%) in the placebo group.

The combination group showed greater improvements in high-resolution computed tomography-evaluated lung involvement and lung fibrosis and patient-reported outcomes, including a statistically significant 3.67-point greater improvement in PROMIS-29 physical function score (4.42 vs. 0.75).

The patients on combination therapy had higher rates of serious adverse events (SAEs), and seven discontinued one or both study drugs early, all in the combined arm. Four combination therapy patients had six SAEs, compared to two placebo patients with three SAEs. In the combination group, SAEs included chest pain, herpes zoster ophthalmicus, nodular basal cell cancer, marginal zone B cell lymphoma, renal crisis, and dyspnea. SAEs in the placebo group were colitis, COVID-19 and hypoxic respiratory failure.

Study design challenges

Nonetheless, Dr. Khanna said the SLS-III data are consistent with the SLS-II findings, with mean improvements in FVC of 2.24% and 2.1%, respectively.

“The next study may be able to replicate what we tried to do, keeping in mind that there are really no MMF-naive patients who are walking around,” Dr. Khanna said. “So the challenge is about the feasibility of recruiting within a trial vs. trying to show a statistical difference between the drug and placebo.”

This study could serve as a foundation for future studies of MMF in patients with SSc-ILD, Robert Spiera, MD, of the Hospital for Special Surgery in New York, said in an interview. “There are lessons to be learned both from the study but also from prior studies looking at MMF use in the background in patients treated with other drugs in clinical trials,” he said.

Dr. Spiera noted that the study had other challenges besides the difficulty in recruiting patients who hadn’t been on MMF therapy. “A great challenge is that the benefit with regard to the impact on the lungs from MMF seems most prominent in the first 6 months to a year to even 2 years that somebody is on the drug,” he said.

The other challenge with this study is that a large proportion of patients had limited systemic disease and relatively lower levels of skin disease compared with other studies of patients on MMF, Dr. Spiera said.

“The optimal treatment of scleroderma-associated lung disease remains a very important and not-adequately met need,” he said. “Particularly, we’re looking for drugs that are tolerable in a patient population that are very prone to GI side effects in general. This study and others have taught us a lot about trial design, and I think more globally this will allow us to move this field forward.”

Dr. Khanna disclosed relationships with Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Horizon Therapeutics USA, Janssen Global Services, Prometheus Biosciences, Mitsubishi Tanabe Pharma Corp., Genentech/Roche, Theraly, and Pfizer. Genentech provided funding for the study and pirfenidone and placebo drugs at no cost.

Dr. Spiera disclosed relationships with GlaxoSmithKline, Boehringer-Ingelheim, Corbus Pharmaceutical, InflaRx, AbbVie/Abbott, Sanofi, Novartis, Chemocentryx, Roche and Vera.

PHILADELPHIA – Aggressive therapy using conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in combination with biologic agents early, soon after a child is diagnosed with polyarticular juvenile idiopathic arthritis (pJIA), enabled more patients to achieve clinical remission and longer times in inactive disease than more conventional therapeutic approaches, 3-year results of prospective, observational study demonstrated.

The results of The Childhood Arthritis and Rheumatology Research Alliance STOP-JIA study, which Yukiko Kimura, MD, presented at the annual meeting of the American College of Rheumatology, showed early combination therapy had benefits, compared with other treatment strategies that were more evident at 3 years than at 1 year of study.

“The STOP-JIA study showed that, after 3 years, patients who started a biologic early on in combination with methotrexate spent more time in inactive disease and achieved clinical remission more often when compared to those started on traditional step-up therapy,” Dr. Kimura, chief of pediatric rheumatology at Hackensack (N.J.) Meridian Health and professor of pediatrics at the Hackensack Meridian School of Medicine, said at a press conference. “This study shows that the treatment of poly-JIA patients receive initially very early on in their disease matters even 3 years after that treatment was started.”

The study compared three CARRA consensus treatment plans (CTP) for untreated pediatric pJIA patients: step-up (SU) – starting conventional synthetic DMARD therapy and adding a biologic if needed after 3 or more months; early-combination (EC) therapy – starting synthetic and biologic DMARDs together; and biologic first (BF) therapy – starting biologic DMARD monotherapy.

Dr. Kimura explained the rationale for the study. “Since biologic treatments were introduced more than 20 years ago, the prognosis for JIA significantly improved. These very effective medicines often work wonders, quickly reducing pain and inflammation in joint disease activity,” she said in the press conference. “What is not known, however, is when is the best time to start these very effective treatments.”

The most common approach is to start with a synthetic DMARD, typically methotrexate, and wait before starting a biologic, Dr. Kimura said.

“But even though methotrexate can work very well by itself, it does not work for every patient, and we don’t know whether waiting months for it to work and then starting a biologic might potentially lessen their effectiveness,” Dr. Kimura added. “We don’t know if there’s a window of opportunity that’s lost while waiting to see whether methotrexate will work.”

The study originally enrolled 400 patients, 297 of whom completed the 3-year visit – 190 in SU, 76 in EC and 31 in BF. At 12 months, the study found no statistically significant difference in clinically inactive disease (CID) between the groups, Dr. Kimura said.

Even at the 3-year visit, the percentage of patients in CID off glucocorticoids and clinical Juvenile Arthritis Disease Activity Score based on 10 joints inactive disease (cJADAS 10 ID) did not differ among the three groups, Dr. Kimura said in presenting the results. “But,” she added, “greater proportions of early-combination CTP group were able to achieve clinical remissions and spend more time with inactive disease in both CID and cJADAS 10.”

A closer look at the outcomes showed some separation between early-combination therapy and the other two treatment plans. The incidence of clinical remission (at any time point over 36 months) was 67.1% in the EC group vs. 49.1% and 47.3%, respectively, in the BF and SU groups, Dr. Kimura said. “The difference between the early-combination and step-up groups was highly significant [P = .007],” she added.

EC also had an edge in the percentage of time patients spent in CID (over 36 months): 39.2% versus 32% and 27.4%, respectively, in the BF and SU groups (P = .006 for EV vs. SU), as well as cJADAS 10 ID (50.6% in EC group vs. 42.8% and 37.5%, respectively in the BF and SU groups; P = .005 for EC vs. SU).

Dr. Kimura said that the STOP JIA trial will continue with longer-term analysis and ongoing monitoring of study patients through the CARRA registry. “These longer-term analyses and readouts will be important because even though the results at 12 months didn’t seem as definitive, it seems the longer we go, the more impact we see of the treatments that were started early on in this disease.”

The findings from this study are “significantly important,” Nina T. Washington, MD, MPH, a pediatric rheumatologist at the University of New Mexico Hospital, Albuquerque, and the Mary Bridge Children’s Hospital in Tacoma, Wash., said in an interview. “At least for the past decade we’ve really been advocating towards earlier and aggressive therapy, and that’s what this study shows: the sooner you can treat this disease, the sooner you can attack those joints that are inflamed, the better outcome you give the patient.”

The study also confirms that pediatric rheumatologists are not overtreating patients with pJIA, she added.

“In a sense we’re actually treating and preventing and if you have a child that has arthritis, it’s okay to treat that child,” Dr. Washington said. “For me that’s the most reassuring thing: that I’m not necessarily going overboard. If I have a child with polyarticular JIA and they have multiple inflamed joints and I have the evidence as they’re sitting in front of me, and I treat them. I’m going to give them the best outcome.”

The Patient Centered Outcomes Research Institute provided study funding. Dr. Kimura is chair of the CARRA JIA disease research committee and cochair of the CARRA Registry and Research Oversight Committee. She disclosed a financial relationship with Genentech. Dr. Washington has no relevant relationships to disclose.
 

PHILADELPHIA – Aggressive therapy using conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in combination with biologic agents early, soon after a child is diagnosed with polyarticular juvenile idiopathic arthritis (pJIA), enabled more patients to achieve clinical remission and longer times in inactive disease than more conventional therapeutic approaches, 3-year results of prospective, observational study demonstrated.

The results of The Childhood Arthritis and Rheumatology Research Alliance STOP-JIA study, which Yukiko Kimura, MD, presented at the annual meeting of the American College of Rheumatology, showed early combination therapy had benefits, compared with other treatment strategies that were more evident at 3 years than at 1 year of study.

“The STOP-JIA study showed that, after 3 years, patients who started a biologic early on in combination with methotrexate spent more time in inactive disease and achieved clinical remission more often when compared to those started on traditional step-up therapy,” Dr. Kimura, chief of pediatric rheumatology at Hackensack (N.J.) Meridian Health and professor of pediatrics at the Hackensack Meridian School of Medicine, said at a press conference. “This study shows that the treatment of poly-JIA patients receive initially very early on in their disease matters even 3 years after that treatment was started.”

The study compared three CARRA consensus treatment plans (CTP) for untreated pediatric pJIA patients: step-up (SU) – starting conventional synthetic DMARD therapy and adding a biologic if needed after 3 or more months; early-combination (EC) therapy – starting synthetic and biologic DMARDs together; and biologic first (BF) therapy – starting biologic DMARD monotherapy.

Dr. Kimura explained the rationale for the study. “Since biologic treatments were introduced more than 20 years ago, the prognosis for JIA significantly improved. These very effective medicines often work wonders, quickly reducing pain and inflammation in joint disease activity,” she said in the press conference. “What is not known, however, is when is the best time to start these very effective treatments.”

The most common approach is to start with a synthetic DMARD, typically methotrexate, and wait before starting a biologic, Dr. Kimura said.

“But even though methotrexate can work very well by itself, it does not work for every patient, and we don’t know whether waiting months for it to work and then starting a biologic might potentially lessen their effectiveness,” Dr. Kimura added. “We don’t know if there’s a window of opportunity that’s lost while waiting to see whether methotrexate will work.”

The study originally enrolled 400 patients, 297 of whom completed the 3-year visit – 190 in SU, 76 in EC and 31 in BF. At 12 months, the study found no statistically significant difference in clinically inactive disease (CID) between the groups, Dr. Kimura said.

Even at the 3-year visit, the percentage of patients in CID off glucocorticoids and clinical Juvenile Arthritis Disease Activity Score based on 10 joints inactive disease (cJADAS 10 ID) did not differ among the three groups, Dr. Kimura said in presenting the results. “But,” she added, “greater proportions of early-combination CTP group were able to achieve clinical remissions and spend more time with inactive disease in both CID and cJADAS 10.”

A closer look at the outcomes showed some separation between early-combination therapy and the other two treatment plans. The incidence of clinical remission (at any time point over 36 months) was 67.1% in the EC group vs. 49.1% and 47.3%, respectively, in the BF and SU groups, Dr. Kimura said. “The difference between the early-combination and step-up groups was highly significant [P = .007],” she added.

EC also had an edge in the percentage of time patients spent in CID (over 36 months): 39.2% versus 32% and 27.4%, respectively, in the BF and SU groups (P = .006 for EV vs. SU), as well as cJADAS 10 ID (50.6% in EC group vs. 42.8% and 37.5%, respectively in the BF and SU groups; P = .005 for EC vs. SU).

Dr. Kimura said that the STOP JIA trial will continue with longer-term analysis and ongoing monitoring of study patients through the CARRA registry. “These longer-term analyses and readouts will be important because even though the results at 12 months didn’t seem as definitive, it seems the longer we go, the more impact we see of the treatments that were started early on in this disease.”

The findings from this study are “significantly important,” Nina T. Washington, MD, MPH, a pediatric rheumatologist at the University of New Mexico Hospital, Albuquerque, and the Mary Bridge Children’s Hospital in Tacoma, Wash., said in an interview. “At least for the past decade we’ve really been advocating towards earlier and aggressive therapy, and that’s what this study shows: the sooner you can treat this disease, the sooner you can attack those joints that are inflamed, the better outcome you give the patient.”

The study also confirms that pediatric rheumatologists are not overtreating patients with pJIA, she added.

“In a sense we’re actually treating and preventing and if you have a child that has arthritis, it’s okay to treat that child,” Dr. Washington said. “For me that’s the most reassuring thing: that I’m not necessarily going overboard. If I have a child with polyarticular JIA and they have multiple inflamed joints and I have the evidence as they’re sitting in front of me, and I treat them. I’m going to give them the best outcome.”

The Patient Centered Outcomes Research Institute provided study funding. Dr. Kimura is chair of the CARRA JIA disease research committee and cochair of the CARRA Registry and Research Oversight Committee. She disclosed a financial relationship with Genentech. Dr. Washington has no relevant relationships to disclose.
 

PHILADELPHIA – Aggressive therapy using conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in combination with biologic agents early, soon after a child is diagnosed with polyarticular juvenile idiopathic arthritis (pJIA), enabled more patients to achieve clinical remission and longer times in inactive disease than more conventional therapeutic approaches, 3-year results of prospective, observational study demonstrated.

The results of The Childhood Arthritis and Rheumatology Research Alliance STOP-JIA study, which Yukiko Kimura, MD, presented at the annual meeting of the American College of Rheumatology, showed early combination therapy had benefits, compared with other treatment strategies that were more evident at 3 years than at 1 year of study.

“The STOP-JIA study showed that, after 3 years, patients who started a biologic early on in combination with methotrexate spent more time in inactive disease and achieved clinical remission more often when compared to those started on traditional step-up therapy,” Dr. Kimura, chief of pediatric rheumatology at Hackensack (N.J.) Meridian Health and professor of pediatrics at the Hackensack Meridian School of Medicine, said at a press conference. “This study shows that the treatment of poly-JIA patients receive initially very early on in their disease matters even 3 years after that treatment was started.”

The study compared three CARRA consensus treatment plans (CTP) for untreated pediatric pJIA patients: step-up (SU) – starting conventional synthetic DMARD therapy and adding a biologic if needed after 3 or more months; early-combination (EC) therapy – starting synthetic and biologic DMARDs together; and biologic first (BF) therapy – starting biologic DMARD monotherapy.

Dr. Kimura explained the rationale for the study. “Since biologic treatments were introduced more than 20 years ago, the prognosis for JIA significantly improved. These very effective medicines often work wonders, quickly reducing pain and inflammation in joint disease activity,” she said in the press conference. “What is not known, however, is when is the best time to start these very effective treatments.”

The most common approach is to start with a synthetic DMARD, typically methotrexate, and wait before starting a biologic, Dr. Kimura said.

“But even though methotrexate can work very well by itself, it does not work for every patient, and we don’t know whether waiting months for it to work and then starting a biologic might potentially lessen their effectiveness,” Dr. Kimura added. “We don’t know if there’s a window of opportunity that’s lost while waiting to see whether methotrexate will work.”

The study originally enrolled 400 patients, 297 of whom completed the 3-year visit – 190 in SU, 76 in EC and 31 in BF. At 12 months, the study found no statistically significant difference in clinically inactive disease (CID) between the groups, Dr. Kimura said.

Even at the 3-year visit, the percentage of patients in CID off glucocorticoids and clinical Juvenile Arthritis Disease Activity Score based on 10 joints inactive disease (cJADAS 10 ID) did not differ among the three groups, Dr. Kimura said in presenting the results. “But,” she added, “greater proportions of early-combination CTP group were able to achieve clinical remissions and spend more time with inactive disease in both CID and cJADAS 10.”

A closer look at the outcomes showed some separation between early-combination therapy and the other two treatment plans. The incidence of clinical remission (at any time point over 36 months) was 67.1% in the EC group vs. 49.1% and 47.3%, respectively, in the BF and SU groups, Dr. Kimura said. “The difference between the early-combination and step-up groups was highly significant [P = .007],” she added.

EC also had an edge in the percentage of time patients spent in CID (over 36 months): 39.2% versus 32% and 27.4%, respectively, in the BF and SU groups (P = .006 for EV vs. SU), as well as cJADAS 10 ID (50.6% in EC group vs. 42.8% and 37.5%, respectively in the BF and SU groups; P = .005 for EC vs. SU).

Dr. Kimura said that the STOP JIA trial will continue with longer-term analysis and ongoing monitoring of study patients through the CARRA registry. “These longer-term analyses and readouts will be important because even though the results at 12 months didn’t seem as definitive, it seems the longer we go, the more impact we see of the treatments that were started early on in this disease.”

The findings from this study are “significantly important,” Nina T. Washington, MD, MPH, a pediatric rheumatologist at the University of New Mexico Hospital, Albuquerque, and the Mary Bridge Children’s Hospital in Tacoma, Wash., said in an interview. “At least for the past decade we’ve really been advocating towards earlier and aggressive therapy, and that’s what this study shows: the sooner you can treat this disease, the sooner you can attack those joints that are inflamed, the better outcome you give the patient.”

The study also confirms that pediatric rheumatologists are not overtreating patients with pJIA, she added.

“In a sense we’re actually treating and preventing and if you have a child that has arthritis, it’s okay to treat that child,” Dr. Washington said. “For me that’s the most reassuring thing: that I’m not necessarily going overboard. If I have a child with polyarticular JIA and they have multiple inflamed joints and I have the evidence as they’re sitting in front of me, and I treat them. I’m going to give them the best outcome.”

The Patient Centered Outcomes Research Institute provided study funding. Dr. Kimura is chair of the CARRA JIA disease research committee and cochair of the CARRA Registry and Research Oversight Committee. She disclosed a financial relationship with Genentech. Dr. Washington has no relevant relationships to disclose.
 

PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.

Doses decreased with changing guidelines

Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.

In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.

The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.

The team conducted a case-crossover study within the Mass General Brigham SLE cohort.

Hospitalizations studied over a decade

Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.

They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.

Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.

Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.

Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.

All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
 

Significantly increased hospitalizations

Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).

The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.

In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”

She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.

Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.

Doses decreased with changing guidelines

Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.

In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.

The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.

The team conducted a case-crossover study within the Mass General Brigham SLE cohort.

Hospitalizations studied over a decade

Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.

They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.

Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.

Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.

Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.

All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
 

Significantly increased hospitalizations

Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).

The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.

In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”

She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.

Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.

Doses decreased with changing guidelines

Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.

In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.

The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.

The team conducted a case-crossover study within the Mass General Brigham SLE cohort.

Hospitalizations studied over a decade

Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.

They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.

Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.

Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.

Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.

All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
 

Significantly increased hospitalizations

Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).

The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.

In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”

She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.

Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – When patients with inflammatory rheumatic diseases were switched from one biosimilar agent to another, treatment retention rates were high, investigators in Denmark reported.

The findings suggest patient-related factors rather than drug-related factors appear to determine whether patients will stay on the new drug, the researchers said.

One year after a Danish government-mandated switch from one infliximab (Remicade) biosimilar to another equally efficacious but less costly biosimilar, 83% of patients who had started therapy on a biosimilar (so-called “originator-naive” patients) stayed on the newly assigned therapy. And so did 92% of patients who had started on the original infliximab (“originator experienced”) before they were switched to one biosimilar and then another.

Neil Osterweil/MDedge News

“In regards to potential baseline predictors, we found that treatment withdrawal was more frequent among originator-naive switchers and patients with higher baseline disease activity, especially [in] patient-reported outcomes, which may indicate that treatment-related outcomes may be more affected by patient-related rather than drug-related factors,” said lead author Hafsah Nabi, MD from the Danish biosimilar registry DANBIO and a PhD candidate at the Copenhagen Center for Arthritis Research.

Dr. Nabi reported the results in an oral abstract session at the annual meeting of the American College of Rheumatology.
 

Annual review of biologic agents

In Denmark, health authorities issue annual recommendations for the use of biologic agents. “And since patients receive this treatment free from the hospital, based on the tax system, the switches are made due to these cost considerations,” Dr. Nabi said in an interview.

Neil Osterweil/MDedge News

To get the nod from Danish pharmaceutical regulators, pharmaceutical manufacturers submit drugs that have already been approved by the European Medicines Agency for consideration for treatment of specific indications, explained coauthor Merete Lund Hetland, MD, PhD, DMSc, from Rigshospitalet in Copenhagen.

“Those drugs that are then considered equally safe and effective are invited to this process where they will give their bid, and then the cheapest one will win,” she said.

The winning formulation will be able to capture about 80% of prescriptions for that indication for the coming year.
 

Awake at the switch

Dr. Nabi, Dr. Hetland, and colleagues studied how one such recent government-mandated switch from one biosimilar to another affected efficacy and patterns of care among patients with rheumatoid arthritis, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).

To identify prior comorbidities, they drew data from the DANBIO registry, which is linked to patient specific but anonymous data from other comprehensive birth-to-death patient registries in Denmark.

They looked at all patients with RA, PsA, or axSpA who were switched from CT-P13 (Remsira, Inflectra) to GP1111 (Zessly) from April 1, 2019, to Feb. 1, 2020.

They identified a total of 1,605 patients, including 685 with RA, 314 with PsA, and 606 with axSpa. The median disease duration was 9 years, and 37% of all patients were in remission according to Clinical Disease Activity Index or Ankylosing Spondylitis Disease Activity Scale.

Of this group, 1,171 had started therapy on a biosimilar.

As noted above, 83% of patients who had never received original infliximab, and 92% of those who were originator experienced were still on the new biosimilar 1 year after the switch.

In a multivariate analysis controlling for demographic and clinical factors at baseline, the variables significantly associated with treatment withdrawal from the new biosimilar (GP11110) included previous Remicade exposure (hazard ratio, 0.36), methotrexate use (HR, 0.60), and patient-reported global visual analog scale (HR, 1.02).

Among all patients, disease activity was stable 6 months before and after the switch, Dr. Nabi said, although she did not show data to support it.
 

Patient education benefit

During the session, Jonathan Kay, MD, professor of rheumatology and chair of the division of rheumatology at the University of Massachusetts, Worcester, who was not involved the study, asked Dr. Nabi whether patients were educated about equivalent efficacy and safety of biosimilars prior to the switch. He noted that education prior to switching led to a much lower patient withdrawal rate in a similar switching study conducted in The Netherlands.

“In this study, we haven’t looked more specifically into the education and which strategies have been used prior to switching, and we also conclude in the study that there may be the presence of a nocebo effect, which can be handled by better educating the patients,” she replied.

The nocebo effect refers to the phenomenon in which a patient’s belief that a specific intervention may cause harm actually can lead to negative outcomes – in other words, the opposite of the placebo effect.

In an interview, Dr. Kay said that he is confident about the efficacy, safety, and equivalency of approved biosimilar agents.

“A biosimilar that has been reviewed and approved by a regulatory agency such as the [Food and Drug Administration or the [European Medicines Agency] should be equivalent in efficacy and comparable in safety and immunogenicity. I would be fully confident in switching from the reference product to the biosimilar,” he said.

Dr. Nabi reported that the study was partly funded by a research grant from Sandoz, the maker of GP1111. Dr. Hetland has disclosed grants from various companies, not including Sandoz. Dr. Kay disclosed consulting fees from various companies, not including Sandoz.

PHILADELPHIA – When patients with inflammatory rheumatic diseases were switched from one biosimilar agent to another, treatment retention rates were high, investigators in Denmark reported.

The findings suggest patient-related factors rather than drug-related factors appear to determine whether patients will stay on the new drug, the researchers said.

One year after a Danish government-mandated switch from one infliximab (Remicade) biosimilar to another equally efficacious but less costly biosimilar, 83% of patients who had started therapy on a biosimilar (so-called “originator-naive” patients) stayed on the newly assigned therapy. And so did 92% of patients who had started on the original infliximab (“originator experienced”) before they were switched to one biosimilar and then another.

Neil Osterweil/MDedge News

“In regards to potential baseline predictors, we found that treatment withdrawal was more frequent among originator-naive switchers and patients with higher baseline disease activity, especially [in] patient-reported outcomes, which may indicate that treatment-related outcomes may be more affected by patient-related rather than drug-related factors,” said lead author Hafsah Nabi, MD from the Danish biosimilar registry DANBIO and a PhD candidate at the Copenhagen Center for Arthritis Research.

Dr. Nabi reported the results in an oral abstract session at the annual meeting of the American College of Rheumatology.
 

Annual review of biologic agents

In Denmark, health authorities issue annual recommendations for the use of biologic agents. “And since patients receive this treatment free from the hospital, based on the tax system, the switches are made due to these cost considerations,” Dr. Nabi said in an interview.

Neil Osterweil/MDedge News

To get the nod from Danish pharmaceutical regulators, pharmaceutical manufacturers submit drugs that have already been approved by the European Medicines Agency for consideration for treatment of specific indications, explained coauthor Merete Lund Hetland, MD, PhD, DMSc, from Rigshospitalet in Copenhagen.

“Those drugs that are then considered equally safe and effective are invited to this process where they will give their bid, and then the cheapest one will win,” she said.

The winning formulation will be able to capture about 80% of prescriptions for that indication for the coming year.
 

Awake at the switch

Dr. Nabi, Dr. Hetland, and colleagues studied how one such recent government-mandated switch from one biosimilar to another affected efficacy and patterns of care among patients with rheumatoid arthritis, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).

To identify prior comorbidities, they drew data from the DANBIO registry, which is linked to patient specific but anonymous data from other comprehensive birth-to-death patient registries in Denmark.

They looked at all patients with RA, PsA, or axSpA who were switched from CT-P13 (Remsira, Inflectra) to GP1111 (Zessly) from April 1, 2019, to Feb. 1, 2020.

They identified a total of 1,605 patients, including 685 with RA, 314 with PsA, and 606 with axSpa. The median disease duration was 9 years, and 37% of all patients were in remission according to Clinical Disease Activity Index or Ankylosing Spondylitis Disease Activity Scale.

Of this group, 1,171 had started therapy on a biosimilar.

As noted above, 83% of patients who had never received original infliximab, and 92% of those who were originator experienced were still on the new biosimilar 1 year after the switch.

In a multivariate analysis controlling for demographic and clinical factors at baseline, the variables significantly associated with treatment withdrawal from the new biosimilar (GP11110) included previous Remicade exposure (hazard ratio, 0.36), methotrexate use (HR, 0.60), and patient-reported global visual analog scale (HR, 1.02).

Among all patients, disease activity was stable 6 months before and after the switch, Dr. Nabi said, although she did not show data to support it.
 

Patient education benefit

During the session, Jonathan Kay, MD, professor of rheumatology and chair of the division of rheumatology at the University of Massachusetts, Worcester, who was not involved the study, asked Dr. Nabi whether patients were educated about equivalent efficacy and safety of biosimilars prior to the switch. He noted that education prior to switching led to a much lower patient withdrawal rate in a similar switching study conducted in The Netherlands.

“In this study, we haven’t looked more specifically into the education and which strategies have been used prior to switching, and we also conclude in the study that there may be the presence of a nocebo effect, which can be handled by better educating the patients,” she replied.

The nocebo effect refers to the phenomenon in which a patient’s belief that a specific intervention may cause harm actually can lead to negative outcomes – in other words, the opposite of the placebo effect.

In an interview, Dr. Kay said that he is confident about the efficacy, safety, and equivalency of approved biosimilar agents.

“A biosimilar that has been reviewed and approved by a regulatory agency such as the [Food and Drug Administration or the [European Medicines Agency] should be equivalent in efficacy and comparable in safety and immunogenicity. I would be fully confident in switching from the reference product to the biosimilar,” he said.

Dr. Nabi reported that the study was partly funded by a research grant from Sandoz, the maker of GP1111. Dr. Hetland has disclosed grants from various companies, not including Sandoz. Dr. Kay disclosed consulting fees from various companies, not including Sandoz.

PHILADELPHIA – When patients with inflammatory rheumatic diseases were switched from one biosimilar agent to another, treatment retention rates were high, investigators in Denmark reported.

The findings suggest patient-related factors rather than drug-related factors appear to determine whether patients will stay on the new drug, the researchers said.

One year after a Danish government-mandated switch from one infliximab (Remicade) biosimilar to another equally efficacious but less costly biosimilar, 83% of patients who had started therapy on a biosimilar (so-called “originator-naive” patients) stayed on the newly assigned therapy. And so did 92% of patients who had started on the original infliximab (“originator experienced”) before they were switched to one biosimilar and then another.

Neil Osterweil/MDedge News

“In regards to potential baseline predictors, we found that treatment withdrawal was more frequent among originator-naive switchers and patients with higher baseline disease activity, especially [in] patient-reported outcomes, which may indicate that treatment-related outcomes may be more affected by patient-related rather than drug-related factors,” said lead author Hafsah Nabi, MD from the Danish biosimilar registry DANBIO and a PhD candidate at the Copenhagen Center for Arthritis Research.

Dr. Nabi reported the results in an oral abstract session at the annual meeting of the American College of Rheumatology.
 

Annual review of biologic agents

In Denmark, health authorities issue annual recommendations for the use of biologic agents. “And since patients receive this treatment free from the hospital, based on the tax system, the switches are made due to these cost considerations,” Dr. Nabi said in an interview.

Neil Osterweil/MDedge News

To get the nod from Danish pharmaceutical regulators, pharmaceutical manufacturers submit drugs that have already been approved by the European Medicines Agency for consideration for treatment of specific indications, explained coauthor Merete Lund Hetland, MD, PhD, DMSc, from Rigshospitalet in Copenhagen.

“Those drugs that are then considered equally safe and effective are invited to this process where they will give their bid, and then the cheapest one will win,” she said.

The winning formulation will be able to capture about 80% of prescriptions for that indication for the coming year.
 

Awake at the switch

Dr. Nabi, Dr. Hetland, and colleagues studied how one such recent government-mandated switch from one biosimilar to another affected efficacy and patterns of care among patients with rheumatoid arthritis, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).

To identify prior comorbidities, they drew data from the DANBIO registry, which is linked to patient specific but anonymous data from other comprehensive birth-to-death patient registries in Denmark.

They looked at all patients with RA, PsA, or axSpA who were switched from CT-P13 (Remsira, Inflectra) to GP1111 (Zessly) from April 1, 2019, to Feb. 1, 2020.

They identified a total of 1,605 patients, including 685 with RA, 314 with PsA, and 606 with axSpa. The median disease duration was 9 years, and 37% of all patients were in remission according to Clinical Disease Activity Index or Ankylosing Spondylitis Disease Activity Scale.

Of this group, 1,171 had started therapy on a biosimilar.

As noted above, 83% of patients who had never received original infliximab, and 92% of those who were originator experienced were still on the new biosimilar 1 year after the switch.

In a multivariate analysis controlling for demographic and clinical factors at baseline, the variables significantly associated with treatment withdrawal from the new biosimilar (GP11110) included previous Remicade exposure (hazard ratio, 0.36), methotrexate use (HR, 0.60), and patient-reported global visual analog scale (HR, 1.02).

Among all patients, disease activity was stable 6 months before and after the switch, Dr. Nabi said, although she did not show data to support it.
 

Patient education benefit

During the session, Jonathan Kay, MD, professor of rheumatology and chair of the division of rheumatology at the University of Massachusetts, Worcester, who was not involved the study, asked Dr. Nabi whether patients were educated about equivalent efficacy and safety of biosimilars prior to the switch. He noted that education prior to switching led to a much lower patient withdrawal rate in a similar switching study conducted in The Netherlands.

“In this study, we haven’t looked more specifically into the education and which strategies have been used prior to switching, and we also conclude in the study that there may be the presence of a nocebo effect, which can be handled by better educating the patients,” she replied.

The nocebo effect refers to the phenomenon in which a patient’s belief that a specific intervention may cause harm actually can lead to negative outcomes – in other words, the opposite of the placebo effect.

In an interview, Dr. Kay said that he is confident about the efficacy, safety, and equivalency of approved biosimilar agents.

“A biosimilar that has been reviewed and approved by a regulatory agency such as the [Food and Drug Administration or the [European Medicines Agency] should be equivalent in efficacy and comparable in safety and immunogenicity. I would be fully confident in switching from the reference product to the biosimilar,” he said.

Dr. Nabi reported that the study was partly funded by a research grant from Sandoz, the maker of GP1111. Dr. Hetland has disclosed grants from various companies, not including Sandoz. Dr. Kay disclosed consulting fees from various companies, not including Sandoz.

PHILADELPHIA – In the first controlled clinical trial to compare the two drugs, rituximab and cyclophosphamide were similarly effective in improving lung function in patients with interstitial lung disease (ILD) associated with idiopathic inflammatory myositis and mixed connective tissue disease (CTD). The findings also revealed some nuanced findings that could help clarify which drug to use in specific patients.

“We feel that rituximab is a reasonable alternative to cyclophosphamide as a treatment in patients with these diseases,” said Toby Maher, MD, of the University of Southern California, Los Angeles, who presented results of an analysis of three disease subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease) study at the annual meeting of the American College of Rheumatology.

“We didn’t show it to be better, so I think you can reasonably choose between the two, but rituximab almost certainly has the advantage of being safer and better tolerated than cyclophosphamide,” Dr. Maher said in an interview. The findings were published simultaneously in The Lancet Respiratory Medicine.
 

Double-blind, double-dummy

RECITAL is a phase 2b, randomized, controlled trial to test the hypothesis that intravenous rituximab would be superior to cyclophosphamide for ILD-associated CTD.

The study included adults with three separate diagnoses: myositis (n = 44), mixed CTD (n = 16), and systemic sclerosis (SSc, n = 37). The study was done in the United Kingdom when Dr. Maher was with Imperial College London.

Patients in the rituximab group received 1,000 mg of IV treatment at baseline and 2 weeks, then placebo treatment every 4 weeks to week 20. Cyclophosphamide patients received 600 mg/m² of body surface area intravenously every 4 weeks for six doses.

“When we designed this study there was limited evidence for any treatment for any disease associated with ILD,” Dr. Maher said. “But cyclophosphamide brings with it many challenges. It can be poorly tolerated and carries issues like infertility and risk of bladder cancer.”
 

Improved lung function

While the study failed to meet its primary endpoint – superiority of rituximab versus cyclophosphamide – it did show that both drugs led to improvement in lung function, measured by the rate of change in forced vital capacity (FVC), as well as quality of life measures, Dr. Maher said.

“Overall by week 48, we saw about a 5% improvement in FVC in the cyclophosphamide group and approximately a 4% improvement in FVC from baseline in the rituximab group, suggesting that both drugs almost certainly had a positive benefit in this patient group,” he said.

But secondary outcomes varied somewhat across the different disease groups. Patients with SSc saw a slight deterioration with cyclophosphamide in the modified Rodnan skin score at 24 weeks (1.6 ± 5.7 units) but an improvement with rituximab (–3.4 ± 8.1 units).

“One area where we did see a difference was in the number of adverse events,” Dr. Maher said. “They were fewer in the rituximab arm – namely gastrointestinal disorders [and] nausea, which we saw quite frequently following cyclophosphamide. Also, they had fewer headaches, which we saw quite frequently following cyclophosphamide.”

Rituximab patients also had fewer infusion reactions, but the number of infections was similar between the two treatment groups, he said.

“The patient group that responded best to treatment was the myositis group,” Dr. Maher said in his presentation. “Cyclophosphamide actually appears to be more effective than rituximab in improving their disease. By the end of 48 weeks, the cyclophosphamide group actually gained about 400 mL in FVC, so a close to 20% improvement.”

The rituximab group had “a little bit of a drop-off” in efficacy from weeks 24 to 48, although the trial didn’t repeat dosing at 6 months, “which is what perhaps one might do in clinical practice,” he said.

Oliver Distler, MD, chair of rheumatology at the University Hospital Zürich, raised questions about concurrent corticosteroid use in study patients that may have caused a “spillover” in the study’s efficacy analysis. But Dr. Maher noted that steroid use was balanced in all treatment arms. Patients in the cyclophosphamide arm averaged 42.9 mg of hydrocortisone daily versus 37.6 mg daily in the rituximab arm. That represents a 12.3% reduction in steroid exposure for the latter.

Dr. Distler noted that the myositis population represented the bulk of those study patients on steroids. “So in the myositis subanalysis we do see a combination of high-dose steroid plus cyclophosphamide and rituximab.”

Dr. Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Dr. Distler disclosed relationships with numerous pharmaceutical companies.






 

PHILADELPHIA – In the first controlled clinical trial to compare the two drugs, rituximab and cyclophosphamide were similarly effective in improving lung function in patients with interstitial lung disease (ILD) associated with idiopathic inflammatory myositis and mixed connective tissue disease (CTD). The findings also revealed some nuanced findings that could help clarify which drug to use in specific patients.

“We feel that rituximab is a reasonable alternative to cyclophosphamide as a treatment in patients with these diseases,” said Toby Maher, MD, of the University of Southern California, Los Angeles, who presented results of an analysis of three disease subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease) study at the annual meeting of the American College of Rheumatology.

“We didn’t show it to be better, so I think you can reasonably choose between the two, but rituximab almost certainly has the advantage of being safer and better tolerated than cyclophosphamide,” Dr. Maher said in an interview. The findings were published simultaneously in The Lancet Respiratory Medicine.
 

Double-blind, double-dummy

RECITAL is a phase 2b, randomized, controlled trial to test the hypothesis that intravenous rituximab would be superior to cyclophosphamide for ILD-associated CTD.

The study included adults with three separate diagnoses: myositis (n = 44), mixed CTD (n = 16), and systemic sclerosis (SSc, n = 37). The study was done in the United Kingdom when Dr. Maher was with Imperial College London.

Patients in the rituximab group received 1,000 mg of IV treatment at baseline and 2 weeks, then placebo treatment every 4 weeks to week 20. Cyclophosphamide patients received 600 mg/m² of body surface area intravenously every 4 weeks for six doses.

“When we designed this study there was limited evidence for any treatment for any disease associated with ILD,” Dr. Maher said. “But cyclophosphamide brings with it many challenges. It can be poorly tolerated and carries issues like infertility and risk of bladder cancer.”
 

Improved lung function

While the study failed to meet its primary endpoint – superiority of rituximab versus cyclophosphamide – it did show that both drugs led to improvement in lung function, measured by the rate of change in forced vital capacity (FVC), as well as quality of life measures, Dr. Maher said.

“Overall by week 48, we saw about a 5% improvement in FVC in the cyclophosphamide group and approximately a 4% improvement in FVC from baseline in the rituximab group, suggesting that both drugs almost certainly had a positive benefit in this patient group,” he said.

But secondary outcomes varied somewhat across the different disease groups. Patients with SSc saw a slight deterioration with cyclophosphamide in the modified Rodnan skin score at 24 weeks (1.6 ± 5.7 units) but an improvement with rituximab (–3.4 ± 8.1 units).

“One area where we did see a difference was in the number of adverse events,” Dr. Maher said. “They were fewer in the rituximab arm – namely gastrointestinal disorders [and] nausea, which we saw quite frequently following cyclophosphamide. Also, they had fewer headaches, which we saw quite frequently following cyclophosphamide.”

Rituximab patients also had fewer infusion reactions, but the number of infections was similar between the two treatment groups, he said.

“The patient group that responded best to treatment was the myositis group,” Dr. Maher said in his presentation. “Cyclophosphamide actually appears to be more effective than rituximab in improving their disease. By the end of 48 weeks, the cyclophosphamide group actually gained about 400 mL in FVC, so a close to 20% improvement.”

The rituximab group had “a little bit of a drop-off” in efficacy from weeks 24 to 48, although the trial didn’t repeat dosing at 6 months, “which is what perhaps one might do in clinical practice,” he said.

Oliver Distler, MD, chair of rheumatology at the University Hospital Zürich, raised questions about concurrent corticosteroid use in study patients that may have caused a “spillover” in the study’s efficacy analysis. But Dr. Maher noted that steroid use was balanced in all treatment arms. Patients in the cyclophosphamide arm averaged 42.9 mg of hydrocortisone daily versus 37.6 mg daily in the rituximab arm. That represents a 12.3% reduction in steroid exposure for the latter.

Dr. Distler noted that the myositis population represented the bulk of those study patients on steroids. “So in the myositis subanalysis we do see a combination of high-dose steroid plus cyclophosphamide and rituximab.”

Dr. Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Dr. Distler disclosed relationships with numerous pharmaceutical companies.






 

PHILADELPHIA – In the first controlled clinical trial to compare the two drugs, rituximab and cyclophosphamide were similarly effective in improving lung function in patients with interstitial lung disease (ILD) associated with idiopathic inflammatory myositis and mixed connective tissue disease (CTD). The findings also revealed some nuanced findings that could help clarify which drug to use in specific patients.

“We feel that rituximab is a reasonable alternative to cyclophosphamide as a treatment in patients with these diseases,” said Toby Maher, MD, of the University of Southern California, Los Angeles, who presented results of an analysis of three disease subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease) study at the annual meeting of the American College of Rheumatology.

“We didn’t show it to be better, so I think you can reasonably choose between the two, but rituximab almost certainly has the advantage of being safer and better tolerated than cyclophosphamide,” Dr. Maher said in an interview. The findings were published simultaneously in The Lancet Respiratory Medicine.
 

Double-blind, double-dummy

RECITAL is a phase 2b, randomized, controlled trial to test the hypothesis that intravenous rituximab would be superior to cyclophosphamide for ILD-associated CTD.

The study included adults with three separate diagnoses: myositis (n = 44), mixed CTD (n = 16), and systemic sclerosis (SSc, n = 37). The study was done in the United Kingdom when Dr. Maher was with Imperial College London.

Patients in the rituximab group received 1,000 mg of IV treatment at baseline and 2 weeks, then placebo treatment every 4 weeks to week 20. Cyclophosphamide patients received 600 mg/m² of body surface area intravenously every 4 weeks for six doses.

“When we designed this study there was limited evidence for any treatment for any disease associated with ILD,” Dr. Maher said. “But cyclophosphamide brings with it many challenges. It can be poorly tolerated and carries issues like infertility and risk of bladder cancer.”
 

Improved lung function

While the study failed to meet its primary endpoint – superiority of rituximab versus cyclophosphamide – it did show that both drugs led to improvement in lung function, measured by the rate of change in forced vital capacity (FVC), as well as quality of life measures, Dr. Maher said.

“Overall by week 48, we saw about a 5% improvement in FVC in the cyclophosphamide group and approximately a 4% improvement in FVC from baseline in the rituximab group, suggesting that both drugs almost certainly had a positive benefit in this patient group,” he said.

But secondary outcomes varied somewhat across the different disease groups. Patients with SSc saw a slight deterioration with cyclophosphamide in the modified Rodnan skin score at 24 weeks (1.6 ± 5.7 units) but an improvement with rituximab (–3.4 ± 8.1 units).

“One area where we did see a difference was in the number of adverse events,” Dr. Maher said. “They were fewer in the rituximab arm – namely gastrointestinal disorders [and] nausea, which we saw quite frequently following cyclophosphamide. Also, they had fewer headaches, which we saw quite frequently following cyclophosphamide.”

Rituximab patients also had fewer infusion reactions, but the number of infections was similar between the two treatment groups, he said.

“The patient group that responded best to treatment was the myositis group,” Dr. Maher said in his presentation. “Cyclophosphamide actually appears to be more effective than rituximab in improving their disease. By the end of 48 weeks, the cyclophosphamide group actually gained about 400 mL in FVC, so a close to 20% improvement.”

The rituximab group had “a little bit of a drop-off” in efficacy from weeks 24 to 48, although the trial didn’t repeat dosing at 6 months, “which is what perhaps one might do in clinical practice,” he said.

Oliver Distler, MD, chair of rheumatology at the University Hospital Zürich, raised questions about concurrent corticosteroid use in study patients that may have caused a “spillover” in the study’s efficacy analysis. But Dr. Maher noted that steroid use was balanced in all treatment arms. Patients in the cyclophosphamide arm averaged 42.9 mg of hydrocortisone daily versus 37.6 mg daily in the rituximab arm. That represents a 12.3% reduction in steroid exposure for the latter.

Dr. Distler noted that the myositis population represented the bulk of those study patients on steroids. “So in the myositis subanalysis we do see a combination of high-dose steroid plus cyclophosphamide and rituximab.”

Dr. Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Dr. Distler disclosed relationships with numerous pharmaceutical companies.






 

Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.

AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).

The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
 

Data limited on child vs. adult characteristics

AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.

Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.

Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).

The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
 

More than 1,000 patients included

Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.

They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.

Differences between age groups included:

• Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
• About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood. 
• More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
• Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.

Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.

“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
 

Bringing children into the clinical discussion

Dr. Bloom said in an interview that many pediatric rheumatologists believe kids with vasculitis are like small adults and should be treated similarly, but she said the picture may be more complex than that.

For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.

“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”

Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”

However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”

Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.

AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).

The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
 

Data limited on child vs. adult characteristics

AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.

Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.

Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).

The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
 

More than 1,000 patients included

Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.

They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.

Differences between age groups included:

• Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
• About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood. 
• More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
• Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.

Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.

“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
 

Bringing children into the clinical discussion

Dr. Bloom said in an interview that many pediatric rheumatologists believe kids with vasculitis are like small adults and should be treated similarly, but she said the picture may be more complex than that.

For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.

“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”

Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”

However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”

Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.

AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).

The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
 

Data limited on child vs. adult characteristics

AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.

Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.

Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).

The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
 

More than 1,000 patients included

Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.

They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.

Differences between age groups included:

• Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
• About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood. 
• More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
• Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.

Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.

“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
 

Bringing children into the clinical discussion

Dr. Bloom said in an interview that many pediatric rheumatologists believe kids with vasculitis are like small adults and should be treated similarly, but she said the picture may be more complex than that.

For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.

“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”

Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”

However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”

Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.