Andrew D. Bowser

A 14-day course of hybrid therapy was as effective as 10-day bismuth quadruple therapy, but with fewer side effects, according to results of a randomized trial conducted in Taiwan.

“However, the former had fewer adverse events than the latter,” investigator Ping-I Hsu, MD, of An Nan Hospital, China Medical University, Taiwan said in a virtual presentation at the annual Digestive Disease Week® (DDW). Some patients in the trial received 14-day high-dose dual therapy, which also had a lower rate of adverse events but a lower eradication rate, compared with quadruple therapy, Dr. Hsu added.

This study confirms previous data showing that hybrid therapy has high eradication rates and a lower frequency of adverse events compared with bismuth quadruple therapy, noted Joseph Adrian L. Buensalido, MD, clinical associate professor of medicine in the division of infectious diseases at the University of the Philippines–Philippine General Hospital in Manila. “Clinicians and specialty/guideline groups may need to start looking at moving to first-line hybrid therapy as opposed to the traditional approach,” Dr. Buensalido said in an interview.
 

Current guidelines and data to date

An American College of Gastroenterology clinical guideline published in 2017 strongly recommends bismuth quadruple therapy, with a duration of 10-14 days, as a first-line treatment option. Hybrid therapy is conditionally recommended as a first-line option in the ACG guideline, while high-dose dual therapy is conditionally recommended as a salvage regimen.

In a prospective, randomized comparative study published in 2017, the eradication rates (93.9%) in patients receiving 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole) were comparable with eradication rates (92.8%) with 14-day hybrid therapy (dual therapy with pantoprazole plus amoxicillin for 7 days, followed by quadruple therapy with pantoprazole, amoxicillin, clarithromycin, and metronidazole for 7 days).

Quadruple therapy had a higher frequency of adverse events, at 55%, compared with 15.7% for hybrid therapy (P < .001). “Whether shortening the treatment duration of bismuth quadruple therapy from 14 days to 10 days can reduce the frequency of adverse effects remains unclear,” Dr. Hsu said in introductory comments to his study.
 

Comparing three approaches

In the multicenter, randomized, open-label superiority trial presented at DDW, Dr. Hsu and colleagues randomly assigned 600 Helicobacter pylori–infected participants in equal numbers to receive 14-day hybrid therapy, 14-day high-dose dual therapy, or 10-day bismuth quadruple therapy.

The hybrid therapy regimen consisted of rabeprazole 20 mg twice a day plus amoxicillin 1 g twice a day for 14 days, with clarithromycin 500 mg and metronidazole 500 mg twice a day in the final 7 days. The high-dose dual therapy regimen consisted of rabeprazole 20 mg and amoxicillin 750 mg four times a day for 14 days. The bismuth quadruple therapy regimen consisted of rabeprazole 20 mg twice a day, tripotassium dicitrato bismuthate 300 mg four times a day, tetracycline 500 mg twice a day, and metronidazole 250 mg four times a day for 10 days.

Investigators assessed H. pylori status 6 weeks following the end of therapy. In an intention-to-treat analysis, the hybrid therapy regimen yielded an eradication rate of 96.5%, which was comparable with the 93.5% eradication rate seen with bismuth quadruple therapy and was significantly higher than the 86.0% eradication rate seen with high-dose dual therapy (P < .001), according to Dr. Hsu. Similar efficacy outcomes were seen in per-protocol analysis.

The frequency of adverse events was lowest with high-dose dual therapy, at 13.0%, according to Dr. Hsu. That was significantly lower than the 25.5% frequency of adverse events with hybrid therapy. Bismuth quadruple therapy had a rate of 34.0%.
 

Antibiotic resistance results

Antibiotic resistance was most common for metronidazole, seen in approximately 28% of the quadruple-therapy group, 34% of the hybrid group, and 37% of the high-dose therapy groups. Clarithromycin resistance occurred in about 23% of quadruple therapy recipients, 16% of hybrid recipients, and 16% of high-dose therapy recipients. Amoxicillin and tetracycline resistance was rare, occurring in approximately 0%-3% of groups.

In the quadruple therapy arm, metronidazole resistance was associated with H. pylori eradication failure, according to Dr. Hsu. The eradication rate was about 96% for those subjects with no metronidazole resistance, and 88% for those with resistance (P = .05). Amoxicillin resistance, although rare in the study, independently predicted eradication failure of high-dose dual therapy, Dr. Hsu said. The eradication rate with high-dose dual therapy was 87.6% for individuals without amoxicillin resistance, and 40.0% in individuals with resistance, according to presented data.

The authors reported no financial disclosures related to their research. Dr. Buensalido has been a speaker for Unilab, BSV Bioscience, and Philcare Pharma, and has received sponsorship from Pfizer.

A 14-day course of hybrid therapy was as effective as 10-day bismuth quadruple therapy, but with fewer side effects, according to results of a randomized trial conducted in Taiwan.

“However, the former had fewer adverse events than the latter,” investigator Ping-I Hsu, MD, of An Nan Hospital, China Medical University, Taiwan said in a virtual presentation at the annual Digestive Disease Week® (DDW). Some patients in the trial received 14-day high-dose dual therapy, which also had a lower rate of adverse events but a lower eradication rate, compared with quadruple therapy, Dr. Hsu added.

This study confirms previous data showing that hybrid therapy has high eradication rates and a lower frequency of adverse events compared with bismuth quadruple therapy, noted Joseph Adrian L. Buensalido, MD, clinical associate professor of medicine in the division of infectious diseases at the University of the Philippines–Philippine General Hospital in Manila. “Clinicians and specialty/guideline groups may need to start looking at moving to first-line hybrid therapy as opposed to the traditional approach,” Dr. Buensalido said in an interview.
 

Current guidelines and data to date

An American College of Gastroenterology clinical guideline published in 2017 strongly recommends bismuth quadruple therapy, with a duration of 10-14 days, as a first-line treatment option. Hybrid therapy is conditionally recommended as a first-line option in the ACG guideline, while high-dose dual therapy is conditionally recommended as a salvage regimen.

In a prospective, randomized comparative study published in 2017, the eradication rates (93.9%) in patients receiving 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole) were comparable with eradication rates (92.8%) with 14-day hybrid therapy (dual therapy with pantoprazole plus amoxicillin for 7 days, followed by quadruple therapy with pantoprazole, amoxicillin, clarithromycin, and metronidazole for 7 days).

Quadruple therapy had a higher frequency of adverse events, at 55%, compared with 15.7% for hybrid therapy (P < .001). “Whether shortening the treatment duration of bismuth quadruple therapy from 14 days to 10 days can reduce the frequency of adverse effects remains unclear,” Dr. Hsu said in introductory comments to his study.
 

Comparing three approaches

In the multicenter, randomized, open-label superiority trial presented at DDW, Dr. Hsu and colleagues randomly assigned 600 Helicobacter pylori–infected participants in equal numbers to receive 14-day hybrid therapy, 14-day high-dose dual therapy, or 10-day bismuth quadruple therapy.

The hybrid therapy regimen consisted of rabeprazole 20 mg twice a day plus amoxicillin 1 g twice a day for 14 days, with clarithromycin 500 mg and metronidazole 500 mg twice a day in the final 7 days. The high-dose dual therapy regimen consisted of rabeprazole 20 mg and amoxicillin 750 mg four times a day for 14 days. The bismuth quadruple therapy regimen consisted of rabeprazole 20 mg twice a day, tripotassium dicitrato bismuthate 300 mg four times a day, tetracycline 500 mg twice a day, and metronidazole 250 mg four times a day for 10 days.

Investigators assessed H. pylori status 6 weeks following the end of therapy. In an intention-to-treat analysis, the hybrid therapy regimen yielded an eradication rate of 96.5%, which was comparable with the 93.5% eradication rate seen with bismuth quadruple therapy and was significantly higher than the 86.0% eradication rate seen with high-dose dual therapy (P < .001), according to Dr. Hsu. Similar efficacy outcomes were seen in per-protocol analysis.

The frequency of adverse events was lowest with high-dose dual therapy, at 13.0%, according to Dr. Hsu. That was significantly lower than the 25.5% frequency of adverse events with hybrid therapy. Bismuth quadruple therapy had a rate of 34.0%.
 

Antibiotic resistance results

Antibiotic resistance was most common for metronidazole, seen in approximately 28% of the quadruple-therapy group, 34% of the hybrid group, and 37% of the high-dose therapy groups. Clarithromycin resistance occurred in about 23% of quadruple therapy recipients, 16% of hybrid recipients, and 16% of high-dose therapy recipients. Amoxicillin and tetracycline resistance was rare, occurring in approximately 0%-3% of groups.

In the quadruple therapy arm, metronidazole resistance was associated with H. pylori eradication failure, according to Dr. Hsu. The eradication rate was about 96% for those subjects with no metronidazole resistance, and 88% for those with resistance (P = .05). Amoxicillin resistance, although rare in the study, independently predicted eradication failure of high-dose dual therapy, Dr. Hsu said. The eradication rate with high-dose dual therapy was 87.6% for individuals without amoxicillin resistance, and 40.0% in individuals with resistance, according to presented data.

The authors reported no financial disclosures related to their research. Dr. Buensalido has been a speaker for Unilab, BSV Bioscience, and Philcare Pharma, and has received sponsorship from Pfizer.

A 14-day course of hybrid therapy was as effective as 10-day bismuth quadruple therapy, but with fewer side effects, according to results of a randomized trial conducted in Taiwan.

“However, the former had fewer adverse events than the latter,” investigator Ping-I Hsu, MD, of An Nan Hospital, China Medical University, Taiwan said in a virtual presentation at the annual Digestive Disease Week® (DDW). Some patients in the trial received 14-day high-dose dual therapy, which also had a lower rate of adverse events but a lower eradication rate, compared with quadruple therapy, Dr. Hsu added.

This study confirms previous data showing that hybrid therapy has high eradication rates and a lower frequency of adverse events compared with bismuth quadruple therapy, noted Joseph Adrian L. Buensalido, MD, clinical associate professor of medicine in the division of infectious diseases at the University of the Philippines–Philippine General Hospital in Manila. “Clinicians and specialty/guideline groups may need to start looking at moving to first-line hybrid therapy as opposed to the traditional approach,” Dr. Buensalido said in an interview.
 

Current guidelines and data to date

An American College of Gastroenterology clinical guideline published in 2017 strongly recommends bismuth quadruple therapy, with a duration of 10-14 days, as a first-line treatment option. Hybrid therapy is conditionally recommended as a first-line option in the ACG guideline, while high-dose dual therapy is conditionally recommended as a salvage regimen.

In a prospective, randomized comparative study published in 2017, the eradication rates (93.9%) in patients receiving 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole) were comparable with eradication rates (92.8%) with 14-day hybrid therapy (dual therapy with pantoprazole plus amoxicillin for 7 days, followed by quadruple therapy with pantoprazole, amoxicillin, clarithromycin, and metronidazole for 7 days).

Quadruple therapy had a higher frequency of adverse events, at 55%, compared with 15.7% for hybrid therapy (P < .001). “Whether shortening the treatment duration of bismuth quadruple therapy from 14 days to 10 days can reduce the frequency of adverse effects remains unclear,” Dr. Hsu said in introductory comments to his study.
 

Comparing three approaches

In the multicenter, randomized, open-label superiority trial presented at DDW, Dr. Hsu and colleagues randomly assigned 600 Helicobacter pylori–infected participants in equal numbers to receive 14-day hybrid therapy, 14-day high-dose dual therapy, or 10-day bismuth quadruple therapy.

The hybrid therapy regimen consisted of rabeprazole 20 mg twice a day plus amoxicillin 1 g twice a day for 14 days, with clarithromycin 500 mg and metronidazole 500 mg twice a day in the final 7 days. The high-dose dual therapy regimen consisted of rabeprazole 20 mg and amoxicillin 750 mg four times a day for 14 days. The bismuth quadruple therapy regimen consisted of rabeprazole 20 mg twice a day, tripotassium dicitrato bismuthate 300 mg four times a day, tetracycline 500 mg twice a day, and metronidazole 250 mg four times a day for 10 days.

Investigators assessed H. pylori status 6 weeks following the end of therapy. In an intention-to-treat analysis, the hybrid therapy regimen yielded an eradication rate of 96.5%, which was comparable with the 93.5% eradication rate seen with bismuth quadruple therapy and was significantly higher than the 86.0% eradication rate seen with high-dose dual therapy (P < .001), according to Dr. Hsu. Similar efficacy outcomes were seen in per-protocol analysis.

The frequency of adverse events was lowest with high-dose dual therapy, at 13.0%, according to Dr. Hsu. That was significantly lower than the 25.5% frequency of adverse events with hybrid therapy. Bismuth quadruple therapy had a rate of 34.0%.
 

Antibiotic resistance results

Antibiotic resistance was most common for metronidazole, seen in approximately 28% of the quadruple-therapy group, 34% of the hybrid group, and 37% of the high-dose therapy groups. Clarithromycin resistance occurred in about 23% of quadruple therapy recipients, 16% of hybrid recipients, and 16% of high-dose therapy recipients. Amoxicillin and tetracycline resistance was rare, occurring in approximately 0%-3% of groups.

In the quadruple therapy arm, metronidazole resistance was associated with H. pylori eradication failure, according to Dr. Hsu. The eradication rate was about 96% for those subjects with no metronidazole resistance, and 88% for those with resistance (P = .05). Amoxicillin resistance, although rare in the study, independently predicted eradication failure of high-dose dual therapy, Dr. Hsu said. The eradication rate with high-dose dual therapy was 87.6% for individuals without amoxicillin resistance, and 40.0% in individuals with resistance, according to presented data.

The authors reported no financial disclosures related to their research. Dr. Buensalido has been a speaker for Unilab, BSV Bioscience, and Philcare Pharma, and has received sponsorship from Pfizer.

While liver transplant outcomes were historically poor in people coinfected with HIV and hepatitis C virus (HCV), they have improved significantly in the era of direct-acting antiviral (DAA) therapy, a recent analysis of U.S. organ transplant data showed.

The availability of highly potent DAA therapy should change how transplant specialists view patients coinfected with HIV/HCV who need a liver transplant, according to researcher Jennifer Wang, MD, chief gastroenterology fellow at the University of Chicago, who presented the results of the analysis at the annual Digestive Disease Week® (DDW). Cumulative graft survival rates since the introduction of DAAs are comparable between transplant recipients with HIV/HCV coinfection and recipients who are both HIV and HCV negative, according to the study.

“Having hepatitis C no longer confers worse patient survival in the DAA era, and this is the main takeaway from our study,” Dr. Wang said.

The study also showed that the number of liver transplants among HIV-infected patients has increased over the past 4-5 years. However, the absolute number remains low at 64 cases in 2019, or less than 1% of all liver transplants that year, and only about one-third of those HIV-positive recipients had HCV coinfection, according to Dr. Wang.

Moreover, relatively few centers are performing liver transplants for patients who are HIV/HCV coinfected, and there is significant geographic variation in where the procedures are done, she said in her presentation.
 

Reassuring data that should prompt referral

Taken together, these results should offer reassurance to transplant centers that patients coinfected with HIV/HCV are no longer at increased risk for poor outcomes after transplantation, said Christine M. Durand, MD, associate professor of medicine at Johns Hopkins University, Baltimore.

“The additional call for action should be beyond the transplantation community to ensure that referrals for liver transplant are where they should be,” Dr. Durand said in an interview.

“With a number of only 64 transplants a year, we’re not doing enough, and there are more patients that could benefit from liver transplants,” added Dr. Durand, who is principal investigator of HOPE in Action, a prospective, multicenter, clinical trial evaluating the safety and survival outcomes of HIV-positive deceased donor liver transplants in HIV-positive recipients.
 

Impact of the HOPE Act

Liver transplantation for HIV-positive patients has increased since the signing of the HIV Organ Policy Equity (HOPE) Act in 2013, according to Dr. Wang.

The HOPE act expanded the donor pool to include HIV-positive deceased donors, which not only increased the donor supply overall, but specifically helped HIV-positive individuals, who experience a higher rate of waiting-list mortality, according to a review on the topic authored by Dr. Durand and coauthors.

However, some transplant centers may be reluctant to do liver transplants in HIV-positive patients coinfected with HCV. That’s because, in previous studies that were conducted before the DAA era, outcomes after liver transplant in HIV/HCV-coinfected patients were inferior to those in patients with HIV but no HCV infection, Dr. Wang said.

Accordingly, Dr. Wang and colleagues analyzed Organ Procurement and Transplantation Network (OPTN) data on adult patients who underwent liver transplants between 2008 and 2019 to see if the introduction of DAAs had leveled the playing field for those with HCV coinfection.
 

Progress in a still-underserved population

The practice of liver transplant in the HIV population has been increasing since the HOPE Act, according to Dr. Wang.

Overall, out of 70,125 liver transplant recipients over the 2008-2019 period, 416 (0.6%) were HIV infected, the data show.

In 2014, 28 liver transplants (0.5%) were performed in HIV-infected individuals, which increased to 64 transplants (0.8%) in 2019, data show. Of those 64 HIV-positive liver transplant recipients in 2019, 23 (35.9%) were coinfected with HCV.

Graft survival has greatly improved, from a 3-year survival of only 58% in patients transplanted before the availability of DAAs to 82% in the DAA era, a difference that was statistically significant, Dr. Wang said.

In the DAA era, there was no significant difference in graft failure outcomes when comparing HIV/HCV-coinfected recipients with uninfected recipients, she added.

The largest proportion of liver transplantations in HIV/HCV-coinfected recipients have been done in OPTN Region 9 (New York), both in the pre- and post-DAA eras, according to Dr. Wang. Several regions have very low numbers or have performed no liver transplants in HIV/HCV-coinfected patients in either era.

“The number of transplant centers participating in liver transplant for coinfected patients is still quite low, so this is a very underserved patient population,” Dr. Wang said.

Dr. Wang provided no financial disclosures related to the research. Dr. Durand receives grants to the institution from Abbvie and GlaxoSmithKline and she receives honoraria from Gilead Sciences for serving on a grant review committee.

While liver transplant outcomes were historically poor in people coinfected with HIV and hepatitis C virus (HCV), they have improved significantly in the era of direct-acting antiviral (DAA) therapy, a recent analysis of U.S. organ transplant data showed.

The availability of highly potent DAA therapy should change how transplant specialists view patients coinfected with HIV/HCV who need a liver transplant, according to researcher Jennifer Wang, MD, chief gastroenterology fellow at the University of Chicago, who presented the results of the analysis at the annual Digestive Disease Week® (DDW). Cumulative graft survival rates since the introduction of DAAs are comparable between transplant recipients with HIV/HCV coinfection and recipients who are both HIV and HCV negative, according to the study.

“Having hepatitis C no longer confers worse patient survival in the DAA era, and this is the main takeaway from our study,” Dr. Wang said.

The study also showed that the number of liver transplants among HIV-infected patients has increased over the past 4-5 years. However, the absolute number remains low at 64 cases in 2019, or less than 1% of all liver transplants that year, and only about one-third of those HIV-positive recipients had HCV coinfection, according to Dr. Wang.

Moreover, relatively few centers are performing liver transplants for patients who are HIV/HCV coinfected, and there is significant geographic variation in where the procedures are done, she said in her presentation.
 

Reassuring data that should prompt referral

Taken together, these results should offer reassurance to transplant centers that patients coinfected with HIV/HCV are no longer at increased risk for poor outcomes after transplantation, said Christine M. Durand, MD, associate professor of medicine at Johns Hopkins University, Baltimore.

“The additional call for action should be beyond the transplantation community to ensure that referrals for liver transplant are where they should be,” Dr. Durand said in an interview.

“With a number of only 64 transplants a year, we’re not doing enough, and there are more patients that could benefit from liver transplants,” added Dr. Durand, who is principal investigator of HOPE in Action, a prospective, multicenter, clinical trial evaluating the safety and survival outcomes of HIV-positive deceased donor liver transplants in HIV-positive recipients.
 

Impact of the HOPE Act

Liver transplantation for HIV-positive patients has increased since the signing of the HIV Organ Policy Equity (HOPE) Act in 2013, according to Dr. Wang.

The HOPE act expanded the donor pool to include HIV-positive deceased donors, which not only increased the donor supply overall, but specifically helped HIV-positive individuals, who experience a higher rate of waiting-list mortality, according to a review on the topic authored by Dr. Durand and coauthors.

However, some transplant centers may be reluctant to do liver transplants in HIV-positive patients coinfected with HCV. That’s because, in previous studies that were conducted before the DAA era, outcomes after liver transplant in HIV/HCV-coinfected patients were inferior to those in patients with HIV but no HCV infection, Dr. Wang said.

Accordingly, Dr. Wang and colleagues analyzed Organ Procurement and Transplantation Network (OPTN) data on adult patients who underwent liver transplants between 2008 and 2019 to see if the introduction of DAAs had leveled the playing field for those with HCV coinfection.
 

Progress in a still-underserved population

The practice of liver transplant in the HIV population has been increasing since the HOPE Act, according to Dr. Wang.

Overall, out of 70,125 liver transplant recipients over the 2008-2019 period, 416 (0.6%) were HIV infected, the data show.

In 2014, 28 liver transplants (0.5%) were performed in HIV-infected individuals, which increased to 64 transplants (0.8%) in 2019, data show. Of those 64 HIV-positive liver transplant recipients in 2019, 23 (35.9%) were coinfected with HCV.

Graft survival has greatly improved, from a 3-year survival of only 58% in patients transplanted before the availability of DAAs to 82% in the DAA era, a difference that was statistically significant, Dr. Wang said.

In the DAA era, there was no significant difference in graft failure outcomes when comparing HIV/HCV-coinfected recipients with uninfected recipients, she added.

The largest proportion of liver transplantations in HIV/HCV-coinfected recipients have been done in OPTN Region 9 (New York), both in the pre- and post-DAA eras, according to Dr. Wang. Several regions have very low numbers or have performed no liver transplants in HIV/HCV-coinfected patients in either era.

“The number of transplant centers participating in liver transplant for coinfected patients is still quite low, so this is a very underserved patient population,” Dr. Wang said.

Dr. Wang provided no financial disclosures related to the research. Dr. Durand receives grants to the institution from Abbvie and GlaxoSmithKline and she receives honoraria from Gilead Sciences for serving on a grant review committee.

While liver transplant outcomes were historically poor in people coinfected with HIV and hepatitis C virus (HCV), they have improved significantly in the era of direct-acting antiviral (DAA) therapy, a recent analysis of U.S. organ transplant data showed.

The availability of highly potent DAA therapy should change how transplant specialists view patients coinfected with HIV/HCV who need a liver transplant, according to researcher Jennifer Wang, MD, chief gastroenterology fellow at the University of Chicago, who presented the results of the analysis at the annual Digestive Disease Week® (DDW). Cumulative graft survival rates since the introduction of DAAs are comparable between transplant recipients with HIV/HCV coinfection and recipients who are both HIV and HCV negative, according to the study.

“Having hepatitis C no longer confers worse patient survival in the DAA era, and this is the main takeaway from our study,” Dr. Wang said.

The study also showed that the number of liver transplants among HIV-infected patients has increased over the past 4-5 years. However, the absolute number remains low at 64 cases in 2019, or less than 1% of all liver transplants that year, and only about one-third of those HIV-positive recipients had HCV coinfection, according to Dr. Wang.

Moreover, relatively few centers are performing liver transplants for patients who are HIV/HCV coinfected, and there is significant geographic variation in where the procedures are done, she said in her presentation.
 

Reassuring data that should prompt referral

Taken together, these results should offer reassurance to transplant centers that patients coinfected with HIV/HCV are no longer at increased risk for poor outcomes after transplantation, said Christine M. Durand, MD, associate professor of medicine at Johns Hopkins University, Baltimore.

“The additional call for action should be beyond the transplantation community to ensure that referrals for liver transplant are where they should be,” Dr. Durand said in an interview.

“With a number of only 64 transplants a year, we’re not doing enough, and there are more patients that could benefit from liver transplants,” added Dr. Durand, who is principal investigator of HOPE in Action, a prospective, multicenter, clinical trial evaluating the safety and survival outcomes of HIV-positive deceased donor liver transplants in HIV-positive recipients.
 

Impact of the HOPE Act

Liver transplantation for HIV-positive patients has increased since the signing of the HIV Organ Policy Equity (HOPE) Act in 2013, according to Dr. Wang.

The HOPE act expanded the donor pool to include HIV-positive deceased donors, which not only increased the donor supply overall, but specifically helped HIV-positive individuals, who experience a higher rate of waiting-list mortality, according to a review on the topic authored by Dr. Durand and coauthors.

However, some transplant centers may be reluctant to do liver transplants in HIV-positive patients coinfected with HCV. That’s because, in previous studies that were conducted before the DAA era, outcomes after liver transplant in HIV/HCV-coinfected patients were inferior to those in patients with HIV but no HCV infection, Dr. Wang said.

Accordingly, Dr. Wang and colleagues analyzed Organ Procurement and Transplantation Network (OPTN) data on adult patients who underwent liver transplants between 2008 and 2019 to see if the introduction of DAAs had leveled the playing field for those with HCV coinfection.
 

Progress in a still-underserved population

The practice of liver transplant in the HIV population has been increasing since the HOPE Act, according to Dr. Wang.

Overall, out of 70,125 liver transplant recipients over the 2008-2019 period, 416 (0.6%) were HIV infected, the data show.

In 2014, 28 liver transplants (0.5%) were performed in HIV-infected individuals, which increased to 64 transplants (0.8%) in 2019, data show. Of those 64 HIV-positive liver transplant recipients in 2019, 23 (35.9%) were coinfected with HCV.

Graft survival has greatly improved, from a 3-year survival of only 58% in patients transplanted before the availability of DAAs to 82% in the DAA era, a difference that was statistically significant, Dr. Wang said.

In the DAA era, there was no significant difference in graft failure outcomes when comparing HIV/HCV-coinfected recipients with uninfected recipients, she added.

The largest proportion of liver transplantations in HIV/HCV-coinfected recipients have been done in OPTN Region 9 (New York), both in the pre- and post-DAA eras, according to Dr. Wang. Several regions have very low numbers or have performed no liver transplants in HIV/HCV-coinfected patients in either era.

“The number of transplant centers participating in liver transplant for coinfected patients is still quite low, so this is a very underserved patient population,” Dr. Wang said.

Dr. Wang provided no financial disclosures related to the research. Dr. Durand receives grants to the institution from Abbvie and GlaxoSmithKline and she receives honoraria from Gilead Sciences for serving on a grant review committee.

Pancreatic cancer clinical trials conducted in the United States over the past few decades have not adequately reported or included racial and ethnic minority populations, results of a recent study suggest.

Adequate inclusion of underrepresented minorities in clinical trials is critical to reducing health care disparities and improving patient outcomes, according to investigator Kelly M. Herremans, MD, a surgical research fellow at the University of Florida in Gainesville. For the trials that did report race and ethnicity, Black, Asian/Pacific Islander, American Indian/Alaskan Native, and Hispanic patients were significantly underrepresented, according to the study, which was reported at the annual Digestive Disease Week® (DDW).

“It is unfortunate that we still have not made much headway regarding diversity in clinical trials in order to truly understand the impact that therapeutics may have on the population as a whole,” Dr. Herremans said in a media briefing. “We need to have an accurate representation of the entire population reflected in these studies.”

Only about half of the U.S. pancreatic cancer studies reported the race of participants, and slightly more than one-third reported ethnicity, Dr. Herremans said. She noted that certain racial and ethnic minorities, and in particular Black Americans, have a higher incidence of pancreatic cancer, are diagnosed at younger ages, and die sooner.

Racial and ethnic differences in pancreatic tumor biology have also been reported. Dr. Herremans said patients of African ancestry have both somatic and germline mutations when compared with other subgroups, meaning they may potentially respond differently to specific treatments. “Having diversity in trial participants is critical to ensuring that these differences can be clinically tested,” she said.
 

Objective data on an uncomfortable truth

This review of pancreatic cancer trials is an “excellent and much needed study,” said Antonio H. Mendoza-Ladd, MD, of the division of gastroenterology at Texas Tech University Health Sciences Center, El Paso. “It contributes objective data that brings to the mainstream an unspoken and uncomfortable truth: Systemic racism, bias, and discrimination exist in the medical system,” Dr. Mendoza-Ladd said in an interview.

Pancreatic cancer is one of deadliest malignancies in the world, and underrepresented minorities bear the brunt of its lethality, according to Dr. Mendoza-Ladd. He said researchers should follow the recommendations of the study authors to ensure that underrepresented minorities are enrolled in clinical trials in sufficient numbers. “Pancreatic cancer does not discriminate by ethnicity or socioeconomic status, even if the medical system does,” he said.
 

Pancreatic cancer trial disparities

In their study, Dr. Herremans and colleagues analyzed 207 clinical trials in the United States for pancreatic ductal adenocarcinoma between 2008 and 2020. They identified the studies using ClinicalTrials.gov, a national registry of clinical trial data, then gathered trial data and demographics on 8,429 participants from reported study results and related publications. Using that data, they were able to evaluate the rates at which race, ethnicity, and gender have been reported over the past few decades, as well as the rates of inclusion of racial and ethnic minorities in the studies.

Fewer than half of the trials (49.3%) reported race, and only about one-third (34.7%) reported ethnicity. By comparison, 99% of the studies reported gender. Results did suggest an increase over time in reporting of race and ethnicity, according to Dr. Herremans, particularly since October 2016, when the Food and Drug Administration clarified its expectations on the collection and reporting of race and ethnicity data in clinical trials. However, the clinical trial data suggest minorities were substantially underrepresented in clinical trials during the study period. “Despite this change, we’re not seeing the actual diversity improve in these clinical trials,” Dr Herremans said in an interview.

Black patients represented 8.2% of clinical trial participants despite constituting 12.4% of U.S. incident pancreatic cancer cases (P < .0001), according to data presented by Dr. Herremans. Likewise, the data show that Hispanic patients account for 8.5% of incident cases but made up 6.0% of clinical trial participants; Asian/Pacific Islanders total 3.3% of U.S. incident pancreatic cancer cases but represented 2.4% of trial participants; and American Indian/Alaskan Native patients constitute 0.4% of incident cases versus being 0.3% of participants (P < .0001 for all). Conversely, Dr. Herremans noted that White patients account for 82.3% of the incident cases but made up 84.7% of total trial participants (P = .002).

Dr. Herremans reported no financial disclosures related to the research. Dr. Mendoza-Ladd reported a relationship with ConMed.

Pancreatic cancer clinical trials conducted in the United States over the past few decades have not adequately reported or included racial and ethnic minority populations, results of a recent study suggest.

Adequate inclusion of underrepresented minorities in clinical trials is critical to reducing health care disparities and improving patient outcomes, according to investigator Kelly M. Herremans, MD, a surgical research fellow at the University of Florida in Gainesville. For the trials that did report race and ethnicity, Black, Asian/Pacific Islander, American Indian/Alaskan Native, and Hispanic patients were significantly underrepresented, according to the study, which was reported at the annual Digestive Disease Week® (DDW).

“It is unfortunate that we still have not made much headway regarding diversity in clinical trials in order to truly understand the impact that therapeutics may have on the population as a whole,” Dr. Herremans said in a media briefing. “We need to have an accurate representation of the entire population reflected in these studies.”

Only about half of the U.S. pancreatic cancer studies reported the race of participants, and slightly more than one-third reported ethnicity, Dr. Herremans said. She noted that certain racial and ethnic minorities, and in particular Black Americans, have a higher incidence of pancreatic cancer, are diagnosed at younger ages, and die sooner.

Racial and ethnic differences in pancreatic tumor biology have also been reported. Dr. Herremans said patients of African ancestry have both somatic and germline mutations when compared with other subgroups, meaning they may potentially respond differently to specific treatments. “Having diversity in trial participants is critical to ensuring that these differences can be clinically tested,” she said.
 

Objective data on an uncomfortable truth

This review of pancreatic cancer trials is an “excellent and much needed study,” said Antonio H. Mendoza-Ladd, MD, of the division of gastroenterology at Texas Tech University Health Sciences Center, El Paso. “It contributes objective data that brings to the mainstream an unspoken and uncomfortable truth: Systemic racism, bias, and discrimination exist in the medical system,” Dr. Mendoza-Ladd said in an interview.

Pancreatic cancer is one of deadliest malignancies in the world, and underrepresented minorities bear the brunt of its lethality, according to Dr. Mendoza-Ladd. He said researchers should follow the recommendations of the study authors to ensure that underrepresented minorities are enrolled in clinical trials in sufficient numbers. “Pancreatic cancer does not discriminate by ethnicity or socioeconomic status, even if the medical system does,” he said.
 

Pancreatic cancer trial disparities

In their study, Dr. Herremans and colleagues analyzed 207 clinical trials in the United States for pancreatic ductal adenocarcinoma between 2008 and 2020. They identified the studies using ClinicalTrials.gov, a national registry of clinical trial data, then gathered trial data and demographics on 8,429 participants from reported study results and related publications. Using that data, they were able to evaluate the rates at which race, ethnicity, and gender have been reported over the past few decades, as well as the rates of inclusion of racial and ethnic minorities in the studies.

Fewer than half of the trials (49.3%) reported race, and only about one-third (34.7%) reported ethnicity. By comparison, 99% of the studies reported gender. Results did suggest an increase over time in reporting of race and ethnicity, according to Dr. Herremans, particularly since October 2016, when the Food and Drug Administration clarified its expectations on the collection and reporting of race and ethnicity data in clinical trials. However, the clinical trial data suggest minorities were substantially underrepresented in clinical trials during the study period. “Despite this change, we’re not seeing the actual diversity improve in these clinical trials,” Dr Herremans said in an interview.

Black patients represented 8.2% of clinical trial participants despite constituting 12.4% of U.S. incident pancreatic cancer cases (P < .0001), according to data presented by Dr. Herremans. Likewise, the data show that Hispanic patients account for 8.5% of incident cases but made up 6.0% of clinical trial participants; Asian/Pacific Islanders total 3.3% of U.S. incident pancreatic cancer cases but represented 2.4% of trial participants; and American Indian/Alaskan Native patients constitute 0.4% of incident cases versus being 0.3% of participants (P < .0001 for all). Conversely, Dr. Herremans noted that White patients account for 82.3% of the incident cases but made up 84.7% of total trial participants (P = .002).

Dr. Herremans reported no financial disclosures related to the research. Dr. Mendoza-Ladd reported a relationship with ConMed.

Pancreatic cancer clinical trials conducted in the United States over the past few decades have not adequately reported or included racial and ethnic minority populations, results of a recent study suggest.

Adequate inclusion of underrepresented minorities in clinical trials is critical to reducing health care disparities and improving patient outcomes, according to investigator Kelly M. Herremans, MD, a surgical research fellow at the University of Florida in Gainesville. For the trials that did report race and ethnicity, Black, Asian/Pacific Islander, American Indian/Alaskan Native, and Hispanic patients were significantly underrepresented, according to the study, which was reported at the annual Digestive Disease Week® (DDW).

“It is unfortunate that we still have not made much headway regarding diversity in clinical trials in order to truly understand the impact that therapeutics may have on the population as a whole,” Dr. Herremans said in a media briefing. “We need to have an accurate representation of the entire population reflected in these studies.”

Only about half of the U.S. pancreatic cancer studies reported the race of participants, and slightly more than one-third reported ethnicity, Dr. Herremans said. She noted that certain racial and ethnic minorities, and in particular Black Americans, have a higher incidence of pancreatic cancer, are diagnosed at younger ages, and die sooner.

Racial and ethnic differences in pancreatic tumor biology have also been reported. Dr. Herremans said patients of African ancestry have both somatic and germline mutations when compared with other subgroups, meaning they may potentially respond differently to specific treatments. “Having diversity in trial participants is critical to ensuring that these differences can be clinically tested,” she said.
 

Objective data on an uncomfortable truth

This review of pancreatic cancer trials is an “excellent and much needed study,” said Antonio H. Mendoza-Ladd, MD, of the division of gastroenterology at Texas Tech University Health Sciences Center, El Paso. “It contributes objective data that brings to the mainstream an unspoken and uncomfortable truth: Systemic racism, bias, and discrimination exist in the medical system,” Dr. Mendoza-Ladd said in an interview.

Pancreatic cancer is one of deadliest malignancies in the world, and underrepresented minorities bear the brunt of its lethality, according to Dr. Mendoza-Ladd. He said researchers should follow the recommendations of the study authors to ensure that underrepresented minorities are enrolled in clinical trials in sufficient numbers. “Pancreatic cancer does not discriminate by ethnicity or socioeconomic status, even if the medical system does,” he said.
 

Pancreatic cancer trial disparities

In their study, Dr. Herremans and colleagues analyzed 207 clinical trials in the United States for pancreatic ductal adenocarcinoma between 2008 and 2020. They identified the studies using ClinicalTrials.gov, a national registry of clinical trial data, then gathered trial data and demographics on 8,429 participants from reported study results and related publications. Using that data, they were able to evaluate the rates at which race, ethnicity, and gender have been reported over the past few decades, as well as the rates of inclusion of racial and ethnic minorities in the studies.

Fewer than half of the trials (49.3%) reported race, and only about one-third (34.7%) reported ethnicity. By comparison, 99% of the studies reported gender. Results did suggest an increase over time in reporting of race and ethnicity, according to Dr. Herremans, particularly since October 2016, when the Food and Drug Administration clarified its expectations on the collection and reporting of race and ethnicity data in clinical trials. However, the clinical trial data suggest minorities were substantially underrepresented in clinical trials during the study period. “Despite this change, we’re not seeing the actual diversity improve in these clinical trials,” Dr Herremans said in an interview.

Black patients represented 8.2% of clinical trial participants despite constituting 12.4% of U.S. incident pancreatic cancer cases (P < .0001), according to data presented by Dr. Herremans. Likewise, the data show that Hispanic patients account for 8.5% of incident cases but made up 6.0% of clinical trial participants; Asian/Pacific Islanders total 3.3% of U.S. incident pancreatic cancer cases but represented 2.4% of trial participants; and American Indian/Alaskan Native patients constitute 0.4% of incident cases versus being 0.3% of participants (P < .0001 for all). Conversely, Dr. Herremans noted that White patients account for 82.3% of the incident cases but made up 84.7% of total trial participants (P = .002).

Dr. Herremans reported no financial disclosures related to the research. Dr. Mendoza-Ladd reported a relationship with ConMed.

Irritable bowel syndrome symptoms improved among patients who endured a prolonged COVID-19 lockdown in Argentina, a finding that was unexpected yet reaffirms the gut-brain connection in this gastrointestinal disorder, according to a coauthor of a study presented at the annual Digestive Disease Week® (DDW).

These patients with irritable bowel syndrome (IBS) reported improvements in disease severity and symptoms during the lockdown that were significant in comparison with the prepandemic period, according to Juan Pablo Stefanolo, MD, a lead author on the study.

The proportion of patients with severe IBS dropped from about 50% to 30%, accompanied by decreases in global and individual symptom scores, according to data presented at the meeting.

Investigators had assumed that IBS symptoms would worsen, fueled by new stresses and pressures related to a nationwide lockdown in Argentina that started in March 19, 2020, and didn’t fully end until November.

Now, the hypothesis has changed, according to Dr. Stefanolo, a physician in the neurogastroenterology and motility section at Hospital de Clínicas José de San Martín, Buenos Aires University.

“We think that probably just staying at home in a more relaxed way, and in a more controlled environment, could have improved those symptoms,” Dr. Stefanolo said in an interview.
 

Impact of lifestyle factors?

This reported decrease in overall severity and symptoms associated with IBS during the pandemic lockdown is an “interesting phenomenon” that deserves further study, said Purna C. Kashyap, MBBS, professor of medicine, physiology, and biomedical engineering at the Mayo Medical School, Rochester, Minn.

Diet, exercise, and other lifestyle factors such as spending more time with family could be contributing to the improvement in symptoms, said Dr. Kashyap, who was not involved in the study.

“A follow-up survey which includes these additional factors could help ascertain why there was an improvement in symptoms and could help with developing effective treatment strategies,” Dr. Kashyap said.

A more detailed follow-up survey is definitely warranted, Dr. Stefanolo said, particularly as Argentina faces new and sweeping pandemic-related restrictions caused by a second-wave COVID-19 surge that now includes more than 30,000 new cases per day.

On May 21, Argentina entered a strict 9-day confinement period as President Alberto Fernández said the country was facing its “worst moment” of the pandemic to date.

Although the circumstances are very unfortunate, worsening pandemic conditions in Argentina are nonetheless a “perfect scenario” to explore in more detail how external stress burden impacts IBS symptoms, said Dr. Stefanolo.
 

Study results

To study the impact of the 2020 mandatory lockdown on gut-brain axis symptomatology in IBS patients, Dr. Stefanolo and coauthors assessed a total of 129 patients with IBS-diarrhea or mixed bowel habits subtype. The mean age of participants was 54 years and 78% were female.

Patients were assessed by online survey or phone interview using the Irritable Bowel Syndrome Severity Scale (IBS-SS), Likert scales for IBS symptoms, and the Bristol Stool Scale, along with other measures of mood and comorbidities.

The proportion of patients with severe IBS dropped from 50% (65 patients) in the prepandemic period to 30% (39 patients) during the lockdown, Dr. Stefanolo and coauthors reported at the virtual DDW meeting. Similarly, mean IBS-SS scores dropped from 278.54 to 212.36 during lockdown, translating into a difference of 65.9 points.

Patients reported improvements in global IBS symptoms, pain, and distention. Stool consistency was also improved, with an average decrease on the Bristol scale of 2 points, according to the report.

Similar improvements from the prepandemic period were observed in anxiety and somatization scores, as well as in symptoms of fibromyalgia and chronic fatigue.

By contrast, headache and pyrosis and/or regurgitation symptoms increased from the prepandemic period, possibly because of weight gain, according to Dr. Stefanolo who said that about 60% of patients reported weight gain during the lockdown.
 

Lifestyle advice

The patients in this study were being seen at a tertiary care center, so they tended to have more severe disease than what would be seen in general clinical practice, according to Dr. Stefanolo. Because of that, he advised caution in extrapolating these results to a broader patient population.

Nevertheless, this study does suggest the potential for lifestyle interventions that could make a difference for the average IBS patient, he said.

“It reinforces that outside stress has something to do with it, and that food maybe has something to do with it,” he said. “I think that giving that advice – try to be more relaxed, and maybe control the quality or the type of food you have – could be great to improve ... those symptoms, maybe.”

The study authors reported no financial disclosures related to the research. Dr. Kashyap reported relationships with Novome Biotechnologies, Otsuka Pharmaceuticals, and Pendulum.

Help your patients better understand IBS and symptoms by sharing AGA patient education at www.gastro.org/IBS.

This article was update May 27, 2021.

Irritable bowel syndrome symptoms improved among patients who endured a prolonged COVID-19 lockdown in Argentina, a finding that was unexpected yet reaffirms the gut-brain connection in this gastrointestinal disorder, according to a coauthor of a study presented at the annual Digestive Disease Week® (DDW).

These patients with irritable bowel syndrome (IBS) reported improvements in disease severity and symptoms during the lockdown that were significant in comparison with the prepandemic period, according to Juan Pablo Stefanolo, MD, a lead author on the study.

The proportion of patients with severe IBS dropped from about 50% to 30%, accompanied by decreases in global and individual symptom scores, according to data presented at the meeting.

Investigators had assumed that IBS symptoms would worsen, fueled by new stresses and pressures related to a nationwide lockdown in Argentina that started in March 19, 2020, and didn’t fully end until November.

Now, the hypothesis has changed, according to Dr. Stefanolo, a physician in the neurogastroenterology and motility section at Hospital de Clínicas José de San Martín, Buenos Aires University.

“We think that probably just staying at home in a more relaxed way, and in a more controlled environment, could have improved those symptoms,” Dr. Stefanolo said in an interview.
 

Impact of lifestyle factors?

This reported decrease in overall severity and symptoms associated with IBS during the pandemic lockdown is an “interesting phenomenon” that deserves further study, said Purna C. Kashyap, MBBS, professor of medicine, physiology, and biomedical engineering at the Mayo Medical School, Rochester, Minn.

Diet, exercise, and other lifestyle factors such as spending more time with family could be contributing to the improvement in symptoms, said Dr. Kashyap, who was not involved in the study.

“A follow-up survey which includes these additional factors could help ascertain why there was an improvement in symptoms and could help with developing effective treatment strategies,” Dr. Kashyap said.

A more detailed follow-up survey is definitely warranted, Dr. Stefanolo said, particularly as Argentina faces new and sweeping pandemic-related restrictions caused by a second-wave COVID-19 surge that now includes more than 30,000 new cases per day.

On May 21, Argentina entered a strict 9-day confinement period as President Alberto Fernández said the country was facing its “worst moment” of the pandemic to date.

Although the circumstances are very unfortunate, worsening pandemic conditions in Argentina are nonetheless a “perfect scenario” to explore in more detail how external stress burden impacts IBS symptoms, said Dr. Stefanolo.
 

Study results

To study the impact of the 2020 mandatory lockdown on gut-brain axis symptomatology in IBS patients, Dr. Stefanolo and coauthors assessed a total of 129 patients with IBS-diarrhea or mixed bowel habits subtype. The mean age of participants was 54 years and 78% were female.

Patients were assessed by online survey or phone interview using the Irritable Bowel Syndrome Severity Scale (IBS-SS), Likert scales for IBS symptoms, and the Bristol Stool Scale, along with other measures of mood and comorbidities.

The proportion of patients with severe IBS dropped from 50% (65 patients) in the prepandemic period to 30% (39 patients) during the lockdown, Dr. Stefanolo and coauthors reported at the virtual DDW meeting. Similarly, mean IBS-SS scores dropped from 278.54 to 212.36 during lockdown, translating into a difference of 65.9 points.

Patients reported improvements in global IBS symptoms, pain, and distention. Stool consistency was also improved, with an average decrease on the Bristol scale of 2 points, according to the report.

Similar improvements from the prepandemic period were observed in anxiety and somatization scores, as well as in symptoms of fibromyalgia and chronic fatigue.

By contrast, headache and pyrosis and/or regurgitation symptoms increased from the prepandemic period, possibly because of weight gain, according to Dr. Stefanolo who said that about 60% of patients reported weight gain during the lockdown.
 

Lifestyle advice

The patients in this study were being seen at a tertiary care center, so they tended to have more severe disease than what would be seen in general clinical practice, according to Dr. Stefanolo. Because of that, he advised caution in extrapolating these results to a broader patient population.

Nevertheless, this study does suggest the potential for lifestyle interventions that could make a difference for the average IBS patient, he said.

“It reinforces that outside stress has something to do with it, and that food maybe has something to do with it,” he said. “I think that giving that advice – try to be more relaxed, and maybe control the quality or the type of food you have – could be great to improve ... those symptoms, maybe.”

The study authors reported no financial disclosures related to the research. Dr. Kashyap reported relationships with Novome Biotechnologies, Otsuka Pharmaceuticals, and Pendulum.

Help your patients better understand IBS and symptoms by sharing AGA patient education at www.gastro.org/IBS.

This article was update May 27, 2021.

Irritable bowel syndrome symptoms improved among patients who endured a prolonged COVID-19 lockdown in Argentina, a finding that was unexpected yet reaffirms the gut-brain connection in this gastrointestinal disorder, according to a coauthor of a study presented at the annual Digestive Disease Week® (DDW).

These patients with irritable bowel syndrome (IBS) reported improvements in disease severity and symptoms during the lockdown that were significant in comparison with the prepandemic period, according to Juan Pablo Stefanolo, MD, a lead author on the study.

The proportion of patients with severe IBS dropped from about 50% to 30%, accompanied by decreases in global and individual symptom scores, according to data presented at the meeting.

Investigators had assumed that IBS symptoms would worsen, fueled by new stresses and pressures related to a nationwide lockdown in Argentina that started in March 19, 2020, and didn’t fully end until November.

Now, the hypothesis has changed, according to Dr. Stefanolo, a physician in the neurogastroenterology and motility section at Hospital de Clínicas José de San Martín, Buenos Aires University.

“We think that probably just staying at home in a more relaxed way, and in a more controlled environment, could have improved those symptoms,” Dr. Stefanolo said in an interview.
 

Impact of lifestyle factors?

This reported decrease in overall severity and symptoms associated with IBS during the pandemic lockdown is an “interesting phenomenon” that deserves further study, said Purna C. Kashyap, MBBS, professor of medicine, physiology, and biomedical engineering at the Mayo Medical School, Rochester, Minn.

Diet, exercise, and other lifestyle factors such as spending more time with family could be contributing to the improvement in symptoms, said Dr. Kashyap, who was not involved in the study.

“A follow-up survey which includes these additional factors could help ascertain why there was an improvement in symptoms and could help with developing effective treatment strategies,” Dr. Kashyap said.

A more detailed follow-up survey is definitely warranted, Dr. Stefanolo said, particularly as Argentina faces new and sweeping pandemic-related restrictions caused by a second-wave COVID-19 surge that now includes more than 30,000 new cases per day.

On May 21, Argentina entered a strict 9-day confinement period as President Alberto Fernández said the country was facing its “worst moment” of the pandemic to date.

Although the circumstances are very unfortunate, worsening pandemic conditions in Argentina are nonetheless a “perfect scenario” to explore in more detail how external stress burden impacts IBS symptoms, said Dr. Stefanolo.
 

Study results

To study the impact of the 2020 mandatory lockdown on gut-brain axis symptomatology in IBS patients, Dr. Stefanolo and coauthors assessed a total of 129 patients with IBS-diarrhea or mixed bowel habits subtype. The mean age of participants was 54 years and 78% were female.

Patients were assessed by online survey or phone interview using the Irritable Bowel Syndrome Severity Scale (IBS-SS), Likert scales for IBS symptoms, and the Bristol Stool Scale, along with other measures of mood and comorbidities.

The proportion of patients with severe IBS dropped from 50% (65 patients) in the prepandemic period to 30% (39 patients) during the lockdown, Dr. Stefanolo and coauthors reported at the virtual DDW meeting. Similarly, mean IBS-SS scores dropped from 278.54 to 212.36 during lockdown, translating into a difference of 65.9 points.

Patients reported improvements in global IBS symptoms, pain, and distention. Stool consistency was also improved, with an average decrease on the Bristol scale of 2 points, according to the report.

Similar improvements from the prepandemic period were observed in anxiety and somatization scores, as well as in symptoms of fibromyalgia and chronic fatigue.

By contrast, headache and pyrosis and/or regurgitation symptoms increased from the prepandemic period, possibly because of weight gain, according to Dr. Stefanolo who said that about 60% of patients reported weight gain during the lockdown.
 

Lifestyle advice

The patients in this study were being seen at a tertiary care center, so they tended to have more severe disease than what would be seen in general clinical practice, according to Dr. Stefanolo. Because of that, he advised caution in extrapolating these results to a broader patient population.

Nevertheless, this study does suggest the potential for lifestyle interventions that could make a difference for the average IBS patient, he said.

“It reinforces that outside stress has something to do with it, and that food maybe has something to do with it,” he said. “I think that giving that advice – try to be more relaxed, and maybe control the quality or the type of food you have – could be great to improve ... those symptoms, maybe.”

The study authors reported no financial disclosures related to the research. Dr. Kashyap reported relationships with Novome Biotechnologies, Otsuka Pharmaceuticals, and Pendulum.

Help your patients better understand IBS and symptoms by sharing AGA patient education at www.gastro.org/IBS.

This article was update May 27, 2021.

Irritable bowel syndrome symptoms improved among patients who endured a prolonged COVID-19 lockdown in Argentina, a finding that was unexpected yet reaffirms the gut-brain connection in this gastrointestinal disorder, according to a coauthor of a study presented at the annual Digestive Disease Week® (DDW).

These patients with irritable bowel syndrome (IBS) reported improvements in disease severity and symptoms during the lockdown that were significant in comparison with the prepandemic period, according to Juan Pablo Stefanolo, MD, a lead author on the study.

The proportion of patients with severe IBS dropped from about 50% to 30%, accompanied by decreases in global and individual symptom scores, according to data presented at the meeting.

Investigators had assumed that IBS symptoms would worsen, fueled by new stresses and pressures related to a nationwide lockdown in Argentina that started in March 19, 2020, and didn’t fully end until November.

Now, the hypothesis has changed, according to Dr. Stefanolo, a physician in the neurogastroenterology and motility section at Hospital de Clínicas José de San Martín, Buenos Aires University.

“We think that probably just staying at home in a more relaxed way, and in a more controlled environment, could have improved those symptoms,” Dr. Stefanolo said in an interview.
 

Impact of lifestyle factors?

This reported decrease in overall severity and symptoms associated with IBS during the pandemic lockdown is an “interesting phenomenon” that deserves further study, said Purna C. Kashyap, MBBS, professor of medicine, physiology, and biomedical engineering at the Mayo Medical School, Rochester, Minn.

Diet, exercise, and other lifestyle factors such as spending more time with family could be contributing to the improvement in symptoms, said Dr. Kashyap, who was not involved in the study.

“A follow-up survey which includes these additional factors could help ascertain why there was an improvement in symptoms and could help with developing effective treatment strategies,” Dr. Kashyap said.

A more detailed follow-up survey is definitely warranted, Dr. Stefanolo said, particularly as Argentina faces new and sweeping pandemic-related restrictions caused by a second-wave COVID-19 surge that now includes more than 30,000 new cases per day.

On May 21, Argentina entered a strict 9-day confinement period as President Alberto Fernández said the country was facing its “worst moment” of the pandemic to date.

Although the circumstances are very unfortunate, worsening pandemic conditions in Argentina are nonetheless a “perfect scenario” to explore in more detail how external stress burden impacts IBS symptoms, said Dr. Stefanolo.
 

Study results

To study the impact of the 2020 mandatory lockdown on gut-brain axis symptomatology in IBS patients, Dr. Stefanolo and coauthors assessed a total of 129 patients with IBS-diarrhea or mixed bowel habits subtype. The mean age of participants was 54 years and 78% were female.

Patients were assessed by online survey or phone interview using the Irritable Bowel Syndrome Severity Scale (IBS-SS), Likert scales for IBS symptoms, and the Bristol Stool Scale, along with other measures of mood and comorbidities.

The proportion of patients with severe IBS dropped from 50% (65 patients) in the prepandemic period to 30% (39 patients) during the lockdown, Dr. Stefanolo and coauthors reported at the virtual DDW meeting. Similarly, mean IBS-SS scores dropped from 278.54 to 212.36 during lockdown, translating into a difference of 65.9 points.

Patients reported improvements in global IBS symptoms, pain, and distention. Stool consistency was also improved, with an average decrease on the Bristol scale of 2 points, according to the report.

Similar improvements from the prepandemic period were observed in anxiety and somatization scores, as well as in symptoms of fibromyalgia and chronic fatigue.

By contrast, headache and pyrosis and/or regurgitation symptoms increased from the prepandemic period, possibly because of weight gain, according to Dr. Stefanolo who said that about 60% of patients reported weight gain during the lockdown.
 

Lifestyle advice

The patients in this study were being seen at a tertiary care center, so they tended to have more severe disease than what would be seen in general clinical practice, according to Dr. Stefanolo. Because of that, he advised caution in extrapolating these results to a broader patient population.

Nevertheless, this study does suggest the potential for lifestyle interventions that could make a difference for the average IBS patient, he said.

“It reinforces that outside stress has something to do with it, and that food maybe has something to do with it,” he said. “I think that giving that advice – try to be more relaxed, and maybe control the quality or the type of food you have – could be great to improve ... those symptoms, maybe.”

The study authors reported no financial disclosures related to the research. Dr. Kashyap reported relationships with Novome Biotechnologies, Otsuka Pharmaceuticals, and Pendulum.

Irritable bowel syndrome symptoms improved among patients who endured a prolonged COVID-19 lockdown in Argentina, a finding that was unexpected yet reaffirms the gut-brain connection in this gastrointestinal disorder, according to a coauthor of a study presented at the annual Digestive Disease Week® (DDW).

These patients with irritable bowel syndrome (IBS) reported improvements in disease severity and symptoms during the lockdown that were significant in comparison with the prepandemic period, according to Juan Pablo Stefanolo, MD, a lead author on the study.

The proportion of patients with severe IBS dropped from about 50% to 30%, accompanied by decreases in global and individual symptom scores, according to data presented at the meeting.

Investigators had assumed that IBS symptoms would worsen, fueled by new stresses and pressures related to a nationwide lockdown in Argentina that started in March 19, 2020, and didn’t fully end until November.

Now, the hypothesis has changed, according to Dr. Stefanolo, a physician in the neurogastroenterology and motility section at Hospital de Clínicas José de San Martín, Buenos Aires University.

“We think that probably just staying at home in a more relaxed way, and in a more controlled environment, could have improved those symptoms,” Dr. Stefanolo said in an interview.
 

Impact of lifestyle factors?

This reported decrease in overall severity and symptoms associated with IBS during the pandemic lockdown is an “interesting phenomenon” that deserves further study, said Purna C. Kashyap, MBBS, professor of medicine, physiology, and biomedical engineering at the Mayo Medical School, Rochester, Minn.

Diet, exercise, and other lifestyle factors such as spending more time with family could be contributing to the improvement in symptoms, said Dr. Kashyap, who was not involved in the study.

“A follow-up survey which includes these additional factors could help ascertain why there was an improvement in symptoms and could help with developing effective treatment strategies,” Dr. Kashyap said.

A more detailed follow-up survey is definitely warranted, Dr. Stefanolo said, particularly as Argentina faces new and sweeping pandemic-related restrictions caused by a second-wave COVID-19 surge that now includes more than 30,000 new cases per day.

On May 21, Argentina entered a strict 9-day confinement period as President Alberto Fernández said the country was facing its “worst moment” of the pandemic to date.

Although the circumstances are very unfortunate, worsening pandemic conditions in Argentina are nonetheless a “perfect scenario” to explore in more detail how external stress burden impacts IBS symptoms, said Dr. Stefanolo.
 

Study results

To study the impact of the 2020 mandatory lockdown on gut-brain axis symptomatology in IBS patients, Dr. Stefanolo and coauthors assessed a total of 129 patients with IBS-diarrhea or mixed bowel habits subtype. The mean age of participants was 54 years and 78% were female.

Patients were assessed by online survey or phone interview using the Irritable Bowel Syndrome Severity Scale (IBS-SS), Likert scales for IBS symptoms, and the Bristol Stool Scale, along with other measures of mood and comorbidities.

The proportion of patients with severe IBS dropped from 50% (65 patients) in the prepandemic period to 30% (39 patients) during the lockdown, Dr. Stefanolo and coauthors reported at the virtual DDW meeting. Similarly, mean IBS-SS scores dropped from 278.54 to 212.36 during lockdown, translating into a difference of 65.9 points.

Patients reported improvements in global IBS symptoms, pain, and distention. Stool consistency was also improved, with an average decrease on the Bristol scale of 2 points, according to the report.

Similar improvements from the prepandemic period were observed in anxiety and somatization scores, as well as in symptoms of fibromyalgia and chronic fatigue.

By contrast, headache and pyrosis and/or regurgitation symptoms increased from the prepandemic period, possibly because of weight gain, according to Dr. Stefanolo who said that about 60% of patients reported weight gain during the lockdown.
 

Lifestyle advice

The patients in this study were being seen at a tertiary care center, so they tended to have more severe disease than what would be seen in general clinical practice, according to Dr. Stefanolo. Because of that, he advised caution in extrapolating these results to a broader patient population.

Nevertheless, this study does suggest the potential for lifestyle interventions that could make a difference for the average IBS patient, he said.

“It reinforces that outside stress has something to do with it, and that food maybe has something to do with it,” he said. “I think that giving that advice – try to be more relaxed, and maybe control the quality or the type of food you have – could be great to improve ... those symptoms, maybe.”

The study authors reported no financial disclosures related to the research. Dr. Kashyap reported relationships with Novome Biotechnologies, Otsuka Pharmaceuticals, and Pendulum.

Irritable bowel syndrome symptoms improved among patients who endured a prolonged COVID-19 lockdown in Argentina, a finding that was unexpected yet reaffirms the gut-brain connection in this gastrointestinal disorder, according to a coauthor of a study presented at the annual Digestive Disease Week® (DDW).

These patients with irritable bowel syndrome (IBS) reported improvements in disease severity and symptoms during the lockdown that were significant in comparison with the prepandemic period, according to Juan Pablo Stefanolo, MD, a lead author on the study.

The proportion of patients with severe IBS dropped from about 50% to 30%, accompanied by decreases in global and individual symptom scores, according to data presented at the meeting.

Investigators had assumed that IBS symptoms would worsen, fueled by new stresses and pressures related to a nationwide lockdown in Argentina that started in March 19, 2020, and didn’t fully end until November.

Now, the hypothesis has changed, according to Dr. Stefanolo, a physician in the neurogastroenterology and motility section at Hospital de Clínicas José de San Martín, Buenos Aires University.

“We think that probably just staying at home in a more relaxed way, and in a more controlled environment, could have improved those symptoms,” Dr. Stefanolo said in an interview.
 

Impact of lifestyle factors?

This reported decrease in overall severity and symptoms associated with IBS during the pandemic lockdown is an “interesting phenomenon” that deserves further study, said Purna C. Kashyap, MBBS, professor of medicine, physiology, and biomedical engineering at the Mayo Medical School, Rochester, Minn.

Diet, exercise, and other lifestyle factors such as spending more time with family could be contributing to the improvement in symptoms, said Dr. Kashyap, who was not involved in the study.

“A follow-up survey which includes these additional factors could help ascertain why there was an improvement in symptoms and could help with developing effective treatment strategies,” Dr. Kashyap said.

A more detailed follow-up survey is definitely warranted, Dr. Stefanolo said, particularly as Argentina faces new and sweeping pandemic-related restrictions caused by a second-wave COVID-19 surge that now includes more than 30,000 new cases per day.

On May 21, Argentina entered a strict 9-day confinement period as President Alberto Fernández said the country was facing its “worst moment” of the pandemic to date.

Although the circumstances are very unfortunate, worsening pandemic conditions in Argentina are nonetheless a “perfect scenario” to explore in more detail how external stress burden impacts IBS symptoms, said Dr. Stefanolo.
 

Study results

To study the impact of the 2020 mandatory lockdown on gut-brain axis symptomatology in IBS patients, Dr. Stefanolo and coauthors assessed a total of 129 patients with IBS-diarrhea or mixed bowel habits subtype. The mean age of participants was 54 years and 78% were female.

Patients were assessed by online survey or phone interview using the Irritable Bowel Syndrome Severity Scale (IBS-SS), Likert scales for IBS symptoms, and the Bristol Stool Scale, along with other measures of mood and comorbidities.

The proportion of patients with severe IBS dropped from 50% (65 patients) in the prepandemic period to 30% (39 patients) during the lockdown, Dr. Stefanolo and coauthors reported at the virtual DDW meeting. Similarly, mean IBS-SS scores dropped from 278.54 to 212.36 during lockdown, translating into a difference of 65.9 points.

Patients reported improvements in global IBS symptoms, pain, and distention. Stool consistency was also improved, with an average decrease on the Bristol scale of 2 points, according to the report.

Similar improvements from the prepandemic period were observed in anxiety and somatization scores, as well as in symptoms of fibromyalgia and chronic fatigue.

By contrast, headache and pyrosis and/or regurgitation symptoms increased from the prepandemic period, possibly because of weight gain, according to Dr. Stefanolo who said that about 60% of patients reported weight gain during the lockdown.
 

Lifestyle advice

The patients in this study were being seen at a tertiary care center, so they tended to have more severe disease than what would be seen in general clinical practice, according to Dr. Stefanolo. Because of that, he advised caution in extrapolating these results to a broader patient population.

Nevertheless, this study does suggest the potential for lifestyle interventions that could make a difference for the average IBS patient, he said.

“It reinforces that outside stress has something to do with it, and that food maybe has something to do with it,” he said. “I think that giving that advice – try to be more relaxed, and maybe control the quality or the type of food you have – could be great to improve ... those symptoms, maybe.”

The study authors reported no financial disclosures related to the research. Dr. Kashyap reported relationships with Novome Biotechnologies, Otsuka Pharmaceuticals, and Pendulum.

While colorectal cancer may be the most common and deadly gastrointestinal malignancy, liver and gastric cancers account for some of the most consistent racial and ethnic disparities, a recent retrospective, cross-sectional analysis of U.S. data suggested.

Liver and gastric cancer incidence and mortality were significantly higher for all racial and ethnic minority groups in the study, compared with non-Hispanic Whites, according to the analysis. Notably, however, non-Hispanic Blacks represented the only group to also have elevated incidence and mortality for pancreatic and colorectal, compared with non-Hispanic Whites, according to investigator Aileen Bui, MD, with the University of California, Los Angeles Health.

These study results highlights the need to address modifiable cancer risk factors and overcome barriers to cancer prevention and care in medically underserved minority populations, Dr. Bui said in a virtual presentation of the results at the annual Digestive Disease Week® (DDW).

“While we cannot infer causation or determine risk factors for certain malignancies from the results of our study, there’s little data to support a strong role of biological or genetic differences between racial and ethnic groups to account for the observed disparities in incidence and mortality for GI cancers,” she said in her presentation.
 

Setting out to explore disparities

Gastrointestinal cancer incidence and mortality remain on the rise, despite significant progress in some areas, including colorectal cancer screening and the introduction of effective treatments for hepatitis C virus, Dr. Bui said.

Incidence and mortality from gastrointestinal cancers are set to increase by 34% and 43%, respectively, by the year 2040, and will remain a significant contributor to cancer incidence and mortality in the United States, according to the researcher.

Gastrointestinal cancer incidence and mortality are known to vary by race and ethnicity, so Dr. Bui and colleagues sought to assess the extent of racial and ethnic disparities for individual gastrointestinal cancer types. They identified more than 140,000 incident cases of colorectal, pancreatic, liver, esophageal, and gastric cancers in the Surveillance, Epidemiology, and End Results database from 2013 to 2017. They also incorporated nearly 185,000 mortality cases for those same types of malignancy from National Center for Health Statistics data from the years 2014 to 2018.
 

Breaking down the numbers

Overall, the incidence of colorectal cancer was highest, at 36.9 (cases per 100,000), followed by pancreatic cancer at 11.0, gastric cancer at 7.1, esophageal cancer at 4.1, and liver cancer at 3.0, Dr. Bui’s data show. The mortality rate was again highest for colorectal cancer, followed by pancreatic, liver, esophageal and gastric cancer.

When compared with non-Hispanic Whites, all racial ethnic minority groups had significantly higher incidence of both liver and gastric cancers, according to Dr. Bui.

The researchers calculated rate ratios for gastrointestinal cancer incidence and mortality, with ratios above 1 indicating a higher incidence relative to non-Hispanic Whites.

Among Hispanics, the incidence rate ratios were 1.83 for both liver and gastric cancers, according to the analysis. Similarly, non-Hispanic Asian Pacific Islanders had IRRs of 2.00 for liver cancer and 1.9 for gastric cancer. Non-Hispanic American Indians and Alaska Natives had IRRs of 2.09 for liver cancer and 1.51 for gastric cancer.

By contrast, non-Hispanic Blacks had significantly higher IRRs not only for liver and gastric cancers, at 1.64 and 1.8, respectively, but also for pancreatic cancer, at 1.18, and colorectal cancer at 1.17, Dr. Bui said.

Similar trends were seen in mortality in the presented data, with all racial and ethnic groups exhibiting significantly increased mortality RRs for liver and gastric cancer, compared with non-Hispanic Whites, but with non-Hispanic Blacks showing significantly increases in RRs for liver (1.66), gastric (2.36), pancreatic (1.22), and colorectal (1.36) cancers.

Esophageal cancer rates of incidence and mortality were both lower in racial and ethnic minority groups, compared with non-Hispanic whites, according to Dr. Bui.
 

Increasing screening and surveillance

While the esophageal cancer data is encouraging, these data otherwise clearly highlight the need to step up efforts to help level gastrointestinal cancer disparities, according to Byron Cryer, MD, professor of internal medicine and associate dean for the office of faculty diversity and development at the University of Texas Southwestern Medical Center, Dallas.

AGA Institute

“Clearly more work needs to be done for the other four cancers,” Dr. Cryer said in an interview.

Screening and surveillance may be key to addressing those disparities, not only for colorectal cancer, but for the liver and gastric cancers for which disparities were seen throughout racial and ethnic groups in this study.

“We know that if we get rid of hepatitis C virus early, you can prevent those downstream complications such as cancer,” Dr. Cryer said. “It’s same thing with the gastric cancer – if we get rid of Helicobacter pylori early on in the infection, we decrease the burden of cancer down downstream years later.”

Dr. Bui provided no financial disclosures related to the research. Dr. Cryer has nothing to disclose.

While colorectal cancer may be the most common and deadly gastrointestinal malignancy, liver and gastric cancers account for some of the most consistent racial and ethnic disparities, a recent retrospective, cross-sectional analysis of U.S. data suggested.

Liver and gastric cancer incidence and mortality were significantly higher for all racial and ethnic minority groups in the study, compared with non-Hispanic Whites, according to the analysis. Notably, however, non-Hispanic Blacks represented the only group to also have elevated incidence and mortality for pancreatic and colorectal, compared with non-Hispanic Whites, according to investigator Aileen Bui, MD, with the University of California, Los Angeles Health.

These study results highlights the need to address modifiable cancer risk factors and overcome barriers to cancer prevention and care in medically underserved minority populations, Dr. Bui said in a virtual presentation of the results at the annual Digestive Disease Week® (DDW).

“While we cannot infer causation or determine risk factors for certain malignancies from the results of our study, there’s little data to support a strong role of biological or genetic differences between racial and ethnic groups to account for the observed disparities in incidence and mortality for GI cancers,” she said in her presentation.
 

Setting out to explore disparities

Gastrointestinal cancer incidence and mortality remain on the rise, despite significant progress in some areas, including colorectal cancer screening and the introduction of effective treatments for hepatitis C virus, Dr. Bui said.

Incidence and mortality from gastrointestinal cancers are set to increase by 34% and 43%, respectively, by the year 2040, and will remain a significant contributor to cancer incidence and mortality in the United States, according to the researcher.

Gastrointestinal cancer incidence and mortality are known to vary by race and ethnicity, so Dr. Bui and colleagues sought to assess the extent of racial and ethnic disparities for individual gastrointestinal cancer types. They identified more than 140,000 incident cases of colorectal, pancreatic, liver, esophageal, and gastric cancers in the Surveillance, Epidemiology, and End Results database from 2013 to 2017. They also incorporated nearly 185,000 mortality cases for those same types of malignancy from National Center for Health Statistics data from the years 2014 to 2018.
 

Breaking down the numbers

Overall, the incidence of colorectal cancer was highest, at 36.9 (cases per 100,000), followed by pancreatic cancer at 11.0, gastric cancer at 7.1, esophageal cancer at 4.1, and liver cancer at 3.0, Dr. Bui’s data show. The mortality rate was again highest for colorectal cancer, followed by pancreatic, liver, esophageal and gastric cancer.

When compared with non-Hispanic Whites, all racial ethnic minority groups had significantly higher incidence of both liver and gastric cancers, according to Dr. Bui.

The researchers calculated rate ratios for gastrointestinal cancer incidence and mortality, with ratios above 1 indicating a higher incidence relative to non-Hispanic Whites.

Among Hispanics, the incidence rate ratios were 1.83 for both liver and gastric cancers, according to the analysis. Similarly, non-Hispanic Asian Pacific Islanders had IRRs of 2.00 for liver cancer and 1.9 for gastric cancer. Non-Hispanic American Indians and Alaska Natives had IRRs of 2.09 for liver cancer and 1.51 for gastric cancer.

By contrast, non-Hispanic Blacks had significantly higher IRRs not only for liver and gastric cancers, at 1.64 and 1.8, respectively, but also for pancreatic cancer, at 1.18, and colorectal cancer at 1.17, Dr. Bui said.

Similar trends were seen in mortality in the presented data, with all racial and ethnic groups exhibiting significantly increased mortality RRs for liver and gastric cancer, compared with non-Hispanic Whites, but with non-Hispanic Blacks showing significantly increases in RRs for liver (1.66), gastric (2.36), pancreatic (1.22), and colorectal (1.36) cancers.

Esophageal cancer rates of incidence and mortality were both lower in racial and ethnic minority groups, compared with non-Hispanic whites, according to Dr. Bui.
 

Increasing screening and surveillance

While the esophageal cancer data is encouraging, these data otherwise clearly highlight the need to step up efforts to help level gastrointestinal cancer disparities, according to Byron Cryer, MD, professor of internal medicine and associate dean for the office of faculty diversity and development at the University of Texas Southwestern Medical Center, Dallas.

AGA Institute

“Clearly more work needs to be done for the other four cancers,” Dr. Cryer said in an interview.

Screening and surveillance may be key to addressing those disparities, not only for colorectal cancer, but for the liver and gastric cancers for which disparities were seen throughout racial and ethnic groups in this study.

“We know that if we get rid of hepatitis C virus early, you can prevent those downstream complications such as cancer,” Dr. Cryer said. “It’s same thing with the gastric cancer – if we get rid of Helicobacter pylori early on in the infection, we decrease the burden of cancer down downstream years later.”

Dr. Bui provided no financial disclosures related to the research. Dr. Cryer has nothing to disclose.

While colorectal cancer may be the most common and deadly gastrointestinal malignancy, liver and gastric cancers account for some of the most consistent racial and ethnic disparities, a recent retrospective, cross-sectional analysis of U.S. data suggested.

Liver and gastric cancer incidence and mortality were significantly higher for all racial and ethnic minority groups in the study, compared with non-Hispanic Whites, according to the analysis. Notably, however, non-Hispanic Blacks represented the only group to also have elevated incidence and mortality for pancreatic and colorectal, compared with non-Hispanic Whites, according to investigator Aileen Bui, MD, with the University of California, Los Angeles Health.

These study results highlights the need to address modifiable cancer risk factors and overcome barriers to cancer prevention and care in medically underserved minority populations, Dr. Bui said in a virtual presentation of the results at the annual Digestive Disease Week® (DDW).

“While we cannot infer causation or determine risk factors for certain malignancies from the results of our study, there’s little data to support a strong role of biological or genetic differences between racial and ethnic groups to account for the observed disparities in incidence and mortality for GI cancers,” she said in her presentation.
 

Setting out to explore disparities

Gastrointestinal cancer incidence and mortality remain on the rise, despite significant progress in some areas, including colorectal cancer screening and the introduction of effective treatments for hepatitis C virus, Dr. Bui said.

Incidence and mortality from gastrointestinal cancers are set to increase by 34% and 43%, respectively, by the year 2040, and will remain a significant contributor to cancer incidence and mortality in the United States, according to the researcher.

Gastrointestinal cancer incidence and mortality are known to vary by race and ethnicity, so Dr. Bui and colleagues sought to assess the extent of racial and ethnic disparities for individual gastrointestinal cancer types. They identified more than 140,000 incident cases of colorectal, pancreatic, liver, esophageal, and gastric cancers in the Surveillance, Epidemiology, and End Results database from 2013 to 2017. They also incorporated nearly 185,000 mortality cases for those same types of malignancy from National Center for Health Statistics data from the years 2014 to 2018.
 

Breaking down the numbers

Overall, the incidence of colorectal cancer was highest, at 36.9 (cases per 100,000), followed by pancreatic cancer at 11.0, gastric cancer at 7.1, esophageal cancer at 4.1, and liver cancer at 3.0, Dr. Bui’s data show. The mortality rate was again highest for colorectal cancer, followed by pancreatic, liver, esophageal and gastric cancer.

When compared with non-Hispanic Whites, all racial ethnic minority groups had significantly higher incidence of both liver and gastric cancers, according to Dr. Bui.

The researchers calculated rate ratios for gastrointestinal cancer incidence and mortality, with ratios above 1 indicating a higher incidence relative to non-Hispanic Whites.

Among Hispanics, the incidence rate ratios were 1.83 for both liver and gastric cancers, according to the analysis. Similarly, non-Hispanic Asian Pacific Islanders had IRRs of 2.00 for liver cancer and 1.9 for gastric cancer. Non-Hispanic American Indians and Alaska Natives had IRRs of 2.09 for liver cancer and 1.51 for gastric cancer.

By contrast, non-Hispanic Blacks had significantly higher IRRs not only for liver and gastric cancers, at 1.64 and 1.8, respectively, but also for pancreatic cancer, at 1.18, and colorectal cancer at 1.17, Dr. Bui said.

Similar trends were seen in mortality in the presented data, with all racial and ethnic groups exhibiting significantly increased mortality RRs for liver and gastric cancer, compared with non-Hispanic Whites, but with non-Hispanic Blacks showing significantly increases in RRs for liver (1.66), gastric (2.36), pancreatic (1.22), and colorectal (1.36) cancers.

Esophageal cancer rates of incidence and mortality were both lower in racial and ethnic minority groups, compared with non-Hispanic whites, according to Dr. Bui.
 

Increasing screening and surveillance

While the esophageal cancer data is encouraging, these data otherwise clearly highlight the need to step up efforts to help level gastrointestinal cancer disparities, according to Byron Cryer, MD, professor of internal medicine and associate dean for the office of faculty diversity and development at the University of Texas Southwestern Medical Center, Dallas.

AGA Institute

“Clearly more work needs to be done for the other four cancers,” Dr. Cryer said in an interview.

Screening and surveillance may be key to addressing those disparities, not only for colorectal cancer, but for the liver and gastric cancers for which disparities were seen throughout racial and ethnic groups in this study.

“We know that if we get rid of hepatitis C virus early, you can prevent those downstream complications such as cancer,” Dr. Cryer said. “It’s same thing with the gastric cancer – if we get rid of Helicobacter pylori early on in the infection, we decrease the burden of cancer down downstream years later.”

Dr. Bui provided no financial disclosures related to the research. Dr. Cryer has nothing to disclose.

High adolescent body mass index is tied to increasing risks of stroke in young adulthood in both men and women, results of a large, population-based cohort study show.

Copyright American Stroke Association

High and even high-normal body mass index (BMI) were linked to increased ischemic stroke risk, regardless of whether or not individuals had diabetes.

Overweight and obese adolescent groups in the study had a roughly two- to threefold increased risk of ischemic stroke, which was apparent even before age 30 years in the study that was based on records of Israeli adolescents evaluated prior to mandatory military service.

These findings highlight the importance of treating and preventing high BMI among adolescence, study coauthor Gilad Twig, MD, MPH, PhD, said in a press release.

“Adults who survive stroke earlier in life face poor functional outcomes, which can lead to unemployment, depression and anxiety,” said Dr. Twig, associate professor in the department of military medicine in The Hebrew University in Jerusalem.

The costs of stroke prevention and care, already high, are expected to become even higher as the adolescent obesity prevalence goes up, fueling further increases in stroke rate, Dr. Twig added.

This is believed to be the first study showing that stroke risk is associated with higher BMI values in both men and women, not just men, Dr. Twig and coauthors said in their article, published May 13, 2021 in the journal Stroke. Previous studies assessing the stroke-BMI relationship in adolescents were based on records of Swedish men evaluated during military conscription at age 18.

In the present study, Dr. Twig and coauthors assessed the linkage between adolescent BMI and first stroke event in 1.9 million male and female adolescents in Israel who were evaluated 1 year prior to mandatory military service, between the years of 1985 and 2013.

They cross-referenced that information with stroke events in a national registry to which all hospitals in Israel are required to report.

The adolescents were about 17 years of age on average at the time of evaluation, 58% were male, and 84% were born in Israel. The mean age at the beginning of follow-up for stroke was about 31 years.

Over the follow-up period, investigators identified 1,088 first stroke events, including 921 ischemic and 167 hemorrhagic strokes.

A gradual increase in stroke rate was seen across BMI categories for ischemic strokes, but not so much for hemorrhagic strokes, investigators found.

Hazard ratios for first ischemic stroke event were 1.4 (95% confidence interval, 1.2-1.6) for the high-normal BMI group, 2.0 (95% CI, 1.6-2.4) for the overweight group, and 3.5 (95% CI, 2.8-4.5) for the obese group after adjusting for age and sex at beginning of follow-up, investigators reported.

When the adjusted results were stratified by presence or absence of diabetes, estimates were similar to what was seen in the overall risk model, they added.

Among those young adults who developed ischemic stroke, 43% smoked, 29% had high blood pressure, 17% had diabetes, and 32% had abnormal lipids at the time of diagnosis, the reported data showed.

The clinical and public health implications of these findings could be substantial, since strokes are associated with worse medical and socioeconomic outcomes in younger as compared with older individuals, according to Dr. Twig and coauthors.

Younger individuals with stroke have a higher risk of recurrent stroke, heart attack, long-term care, or death, they said. Moreover, about half of young-adult stroke survivors have poor functional outcomes, and their risk of unemployment and depression/anxiety is higher than in young individuals without stroke.

One limitation of the study is that follow-up BMI data were not available for all participants. As a result, the contribution of obesity to stroke risk over time could not be assessed, and the independent risk of BMI during adolescence could not be determined. In addition, the authors said the study underrepresents orthodox and ultraorthodox Jewish women, as they are not obligated to serve in the Israeli military.

The study authors had no disclosures related to the study, which was supported by a medical corps Israel Defense Forces research grant.

High adolescent body mass index is tied to increasing risks of stroke in young adulthood in both men and women, results of a large, population-based cohort study show.

Copyright American Stroke Association

High and even high-normal body mass index (BMI) were linked to increased ischemic stroke risk, regardless of whether or not individuals had diabetes.

Overweight and obese adolescent groups in the study had a roughly two- to threefold increased risk of ischemic stroke, which was apparent even before age 30 years in the study that was based on records of Israeli adolescents evaluated prior to mandatory military service.

These findings highlight the importance of treating and preventing high BMI among adolescence, study coauthor Gilad Twig, MD, MPH, PhD, said in a press release.

“Adults who survive stroke earlier in life face poor functional outcomes, which can lead to unemployment, depression and anxiety,” said Dr. Twig, associate professor in the department of military medicine in The Hebrew University in Jerusalem.

The costs of stroke prevention and care, already high, are expected to become even higher as the adolescent obesity prevalence goes up, fueling further increases in stroke rate, Dr. Twig added.

This is believed to be the first study showing that stroke risk is associated with higher BMI values in both men and women, not just men, Dr. Twig and coauthors said in their article, published May 13, 2021 in the journal Stroke. Previous studies assessing the stroke-BMI relationship in adolescents were based on records of Swedish men evaluated during military conscription at age 18.

In the present study, Dr. Twig and coauthors assessed the linkage between adolescent BMI and first stroke event in 1.9 million male and female adolescents in Israel who were evaluated 1 year prior to mandatory military service, between the years of 1985 and 2013.

They cross-referenced that information with stroke events in a national registry to which all hospitals in Israel are required to report.

The adolescents were about 17 years of age on average at the time of evaluation, 58% were male, and 84% were born in Israel. The mean age at the beginning of follow-up for stroke was about 31 years.

Over the follow-up period, investigators identified 1,088 first stroke events, including 921 ischemic and 167 hemorrhagic strokes.

A gradual increase in stroke rate was seen across BMI categories for ischemic strokes, but not so much for hemorrhagic strokes, investigators found.

Hazard ratios for first ischemic stroke event were 1.4 (95% confidence interval, 1.2-1.6) for the high-normal BMI group, 2.0 (95% CI, 1.6-2.4) for the overweight group, and 3.5 (95% CI, 2.8-4.5) for the obese group after adjusting for age and sex at beginning of follow-up, investigators reported.

When the adjusted results were stratified by presence or absence of diabetes, estimates were similar to what was seen in the overall risk model, they added.

Among those young adults who developed ischemic stroke, 43% smoked, 29% had high blood pressure, 17% had diabetes, and 32% had abnormal lipids at the time of diagnosis, the reported data showed.

The clinical and public health implications of these findings could be substantial, since strokes are associated with worse medical and socioeconomic outcomes in younger as compared with older individuals, according to Dr. Twig and coauthors.

Younger individuals with stroke have a higher risk of recurrent stroke, heart attack, long-term care, or death, they said. Moreover, about half of young-adult stroke survivors have poor functional outcomes, and their risk of unemployment and depression/anxiety is higher than in young individuals without stroke.

One limitation of the study is that follow-up BMI data were not available for all participants. As a result, the contribution of obesity to stroke risk over time could not be assessed, and the independent risk of BMI during adolescence could not be determined. In addition, the authors said the study underrepresents orthodox and ultraorthodox Jewish women, as they are not obligated to serve in the Israeli military.

The study authors had no disclosures related to the study, which was supported by a medical corps Israel Defense Forces research grant.

High adolescent body mass index is tied to increasing risks of stroke in young adulthood in both men and women, results of a large, population-based cohort study show.

Copyright American Stroke Association

High and even high-normal body mass index (BMI) were linked to increased ischemic stroke risk, regardless of whether or not individuals had diabetes.

Overweight and obese adolescent groups in the study had a roughly two- to threefold increased risk of ischemic stroke, which was apparent even before age 30 years in the study that was based on records of Israeli adolescents evaluated prior to mandatory military service.

These findings highlight the importance of treating and preventing high BMI among adolescence, study coauthor Gilad Twig, MD, MPH, PhD, said in a press release.

“Adults who survive stroke earlier in life face poor functional outcomes, which can lead to unemployment, depression and anxiety,” said Dr. Twig, associate professor in the department of military medicine in The Hebrew University in Jerusalem.

The costs of stroke prevention and care, already high, are expected to become even higher as the adolescent obesity prevalence goes up, fueling further increases in stroke rate, Dr. Twig added.

This is believed to be the first study showing that stroke risk is associated with higher BMI values in both men and women, not just men, Dr. Twig and coauthors said in their article, published May 13, 2021 in the journal Stroke. Previous studies assessing the stroke-BMI relationship in adolescents were based on records of Swedish men evaluated during military conscription at age 18.

In the present study, Dr. Twig and coauthors assessed the linkage between adolescent BMI and first stroke event in 1.9 million male and female adolescents in Israel who were evaluated 1 year prior to mandatory military service, between the years of 1985 and 2013.

They cross-referenced that information with stroke events in a national registry to which all hospitals in Israel are required to report.

The adolescents were about 17 years of age on average at the time of evaluation, 58% were male, and 84% were born in Israel. The mean age at the beginning of follow-up for stroke was about 31 years.

Over the follow-up period, investigators identified 1,088 first stroke events, including 921 ischemic and 167 hemorrhagic strokes.

A gradual increase in stroke rate was seen across BMI categories for ischemic strokes, but not so much for hemorrhagic strokes, investigators found.

Hazard ratios for first ischemic stroke event were 1.4 (95% confidence interval, 1.2-1.6) for the high-normal BMI group, 2.0 (95% CI, 1.6-2.4) for the overweight group, and 3.5 (95% CI, 2.8-4.5) for the obese group after adjusting for age and sex at beginning of follow-up, investigators reported.

When the adjusted results were stratified by presence or absence of diabetes, estimates were similar to what was seen in the overall risk model, they added.

Among those young adults who developed ischemic stroke, 43% smoked, 29% had high blood pressure, 17% had diabetes, and 32% had abnormal lipids at the time of diagnosis, the reported data showed.

The clinical and public health implications of these findings could be substantial, since strokes are associated with worse medical and socioeconomic outcomes in younger as compared with older individuals, according to Dr. Twig and coauthors.

Younger individuals with stroke have a higher risk of recurrent stroke, heart attack, long-term care, or death, they said. Moreover, about half of young-adult stroke survivors have poor functional outcomes, and their risk of unemployment and depression/anxiety is higher than in young individuals without stroke.

One limitation of the study is that follow-up BMI data were not available for all participants. As a result, the contribution of obesity to stroke risk over time could not be assessed, and the independent risk of BMI during adolescence could not be determined. In addition, the authors said the study underrepresents orthodox and ultraorthodox Jewish women, as they are not obligated to serve in the Israeli military.

The study authors had no disclosures related to the study, which was supported by a medical corps Israel Defense Forces research grant.

For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.

A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.

Reductions in both weight and fat loss seen with exercise and liraglutide was roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine .

Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.
 

Hope for healthy weight loss maintenance

Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.

“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.

“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.

Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.

“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.

“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”
 

Obesity and weight-loss challenges

Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.

The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.

Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.

The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.

The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.

Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.

The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.

Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.

Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.
 

Weight loss with exercise and medication

Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.

The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.

Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.

That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.

A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.

Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.

Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.

The research was supported in part by grants from the Novo Nordisk Foundation.

For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.

A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.

Reductions in both weight and fat loss seen with exercise and liraglutide was roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine .

Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.
 

Hope for healthy weight loss maintenance

Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.

“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.

“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.

Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.

“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.

“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”
 

Obesity and weight-loss challenges

Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.

The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.

Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.

The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.

The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.

Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.

The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.

Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.

Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.
 

Weight loss with exercise and medication

Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.

The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.

Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.

That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.

A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.

Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.

Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.

The research was supported in part by grants from the Novo Nordisk Foundation.

For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.

A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.

Reductions in both weight and fat loss seen with exercise and liraglutide was roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine .

Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.
 

Hope for healthy weight loss maintenance

Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.

“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.

“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.

Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.

“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.

“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”
 

Obesity and weight-loss challenges

Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.

The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.

Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.

The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.

The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.

Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.

The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.

Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.

Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.
 

Weight loss with exercise and medication

Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.

The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.

Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.

That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.

A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.

Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.

Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.

The research was supported in part by grants from the Novo Nordisk Foundation.

Axicabtagene ciloleucel (axi-cel) can be safely administered and has substantial clinical benefit as part of first-line therapy in patients with high-risk large B-cell lymphoma, according to an investigator in a phase 2 study.

The chimeric antigen receptor (CAR) T-cell therapy had a “very high” overall response rate (ORR) of 85% and a complete response (CR) rate of 74% in the ZUMA-12 study, said investigator Sattva S. Neelapu, MD, of The University of Texas MD Anderson Cancer Center in Houston.

Nearly three-quarters of responses were ongoing with a median of follow-up of about 9 months, Dr. Neelapu said in interim analysis of ZUMA-12 presented at the annual meeting of the American Society of Hematology, which was held virtually.

While axi-cel is approved for treatment of certain relapsed/refractory large B-cell lymphomas (LBCLs), Dr. Neelapu said this is the first-ever study evaluating a CAR T-cell therapy as a first-line treatment for patients with LBCL that is high risk as defined by histology or International Prognostic Index (IPI) scoring.

Treatment with axi-cel was guided by dynamic risk assessment, Dr. Neelapu explained, meaning that patients received the CAR T-cell treatment if they had a positive interim positron emission tomography (PET) scan after two cycles of an anti-CD20 monoclonal antibody and anthracycline-containing regimen.
 

Longer follow-up needed

The interim efficacy analysis is based on 27 evaluable patients out of 40 patients planned to be enrolled, meaning that the final analysis is needed, and longer follow-up is needed to ensure that durability is maintained, Dr. Neelapu said in a question-and-answer session following his presentation.

Nevertheless, the 74% complete response rate in the frontline setting is “quite encouraging” compared to historical data in high-risk LBCL, where CR rates have generally been less than 50%, Dr. Neelapu added.

“Assuming that long-term data in the final analysis confirms this encouraging activity, I think we likely would need a randomized phase 3 trial to compare (axi-cel) head-to-head with frontline therapy,” he said.

Without mature data available, it’s hard to say in this single-arm study how much axi-cel is improving outcomes at the cost of significant toxicity, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

Adverse events as reported by Dr. Neelapu included grade 3 cytokine release syndrome (CRS) in 9% of patients, and 25% grade 3 or greater neurologic events in 25%.

“It appears as though it may be salvaging some patients, as the response rate is higher than that expected for chemotherapy alone in this setting,” Dr. Diefenbach said in an interview, “but toxicity is not trivial, so the long-term data will provide better clarity as to the degree of benefit.”
 

Ongoing responses at 9 months

The phase 2 ZUMA-12 study includes patients classified as high risk based on MYC and BCL2 and/or BCL6 translocations, or by an International Prognostic Indicator score of 3 or greater.

Patients initially received two cycles of anti-CD20 monoclonal antibody therapy plus an anthracycline containing regimen. Those with a positive interim PET (score of 4 or 5 on the 5-point Deauville scale) received fludarabine/cyclophosphamide conditioning plus axi-cel as a single intravenous infusion of 2 x 106 CAR T cells per kg of body weight.

As of the report at the ASH meeting, 32 patient had received axi-cel, of whom 32 were evaluable for safety and 27 were evaluable for efficacy.

The ORR was 85% (23 of 27 patients), and the CR rate was 74% (20 of 27 patients), Dr. Neelapu reported, noting that with a median follow-up of 9.3 months, 70% of responders (19 of 27) were in ongoing response.

Median duration of response, progression-free survival, and overall survival have not been reached, he added.

Encephalopathy was the most common grade 3 or greater adverse event related to axi-cel, occurring in 16% of patients, while increased alanine aminotransferase and decreased neutrophil count were each seen in 9% of patients, Dr. Neelapu said.

All 32 patients experienced CRS, including grade 3 CRS in 3 patients (9%), according to the reported data. Neurologic events were seen in 22 patients (69%) including grade 3 or greater in 8 (25%). There were 2 grade 4 neurologic events – both encephalopathies that resolved, according to Dr. Neelapu – and no grade 5 neurologic events.

ZUMA-12 is sponsored by Kite, a Gilead Company. Dr. Neelapu reported disclosures related to Acerta, Adicet Bio, Bristol-Myers Squibb, Kite, and various other pharmaceutical and biotechnology companies.
 

SOURCE: Neelapu SS et al. ASH 2020, Abstract 405.

Axicabtagene ciloleucel (axi-cel) can be safely administered and has substantial clinical benefit as part of first-line therapy in patients with high-risk large B-cell lymphoma, according to an investigator in a phase 2 study.

The chimeric antigen receptor (CAR) T-cell therapy had a “very high” overall response rate (ORR) of 85% and a complete response (CR) rate of 74% in the ZUMA-12 study, said investigator Sattva S. Neelapu, MD, of The University of Texas MD Anderson Cancer Center in Houston.

Nearly three-quarters of responses were ongoing with a median of follow-up of about 9 months, Dr. Neelapu said in interim analysis of ZUMA-12 presented at the annual meeting of the American Society of Hematology, which was held virtually.

While axi-cel is approved for treatment of certain relapsed/refractory large B-cell lymphomas (LBCLs), Dr. Neelapu said this is the first-ever study evaluating a CAR T-cell therapy as a first-line treatment for patients with LBCL that is high risk as defined by histology or International Prognostic Index (IPI) scoring.

Treatment with axi-cel was guided by dynamic risk assessment, Dr. Neelapu explained, meaning that patients received the CAR T-cell treatment if they had a positive interim positron emission tomography (PET) scan after two cycles of an anti-CD20 monoclonal antibody and anthracycline-containing regimen.
 

Longer follow-up needed

The interim efficacy analysis is based on 27 evaluable patients out of 40 patients planned to be enrolled, meaning that the final analysis is needed, and longer follow-up is needed to ensure that durability is maintained, Dr. Neelapu said in a question-and-answer session following his presentation.

Nevertheless, the 74% complete response rate in the frontline setting is “quite encouraging” compared to historical data in high-risk LBCL, where CR rates have generally been less than 50%, Dr. Neelapu added.

“Assuming that long-term data in the final analysis confirms this encouraging activity, I think we likely would need a randomized phase 3 trial to compare (axi-cel) head-to-head with frontline therapy,” he said.

Without mature data available, it’s hard to say in this single-arm study how much axi-cel is improving outcomes at the cost of significant toxicity, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

Adverse events as reported by Dr. Neelapu included grade 3 cytokine release syndrome (CRS) in 9% of patients, and 25% grade 3 or greater neurologic events in 25%.

“It appears as though it may be salvaging some patients, as the response rate is higher than that expected for chemotherapy alone in this setting,” Dr. Diefenbach said in an interview, “but toxicity is not trivial, so the long-term data will provide better clarity as to the degree of benefit.”
 

Ongoing responses at 9 months

The phase 2 ZUMA-12 study includes patients classified as high risk based on MYC and BCL2 and/or BCL6 translocations, or by an International Prognostic Indicator score of 3 or greater.

Patients initially received two cycles of anti-CD20 monoclonal antibody therapy plus an anthracycline containing regimen. Those with a positive interim PET (score of 4 or 5 on the 5-point Deauville scale) received fludarabine/cyclophosphamide conditioning plus axi-cel as a single intravenous infusion of 2 x 106 CAR T cells per kg of body weight.

As of the report at the ASH meeting, 32 patient had received axi-cel, of whom 32 were evaluable for safety and 27 were evaluable for efficacy.

The ORR was 85% (23 of 27 patients), and the CR rate was 74% (20 of 27 patients), Dr. Neelapu reported, noting that with a median follow-up of 9.3 months, 70% of responders (19 of 27) were in ongoing response.

Median duration of response, progression-free survival, and overall survival have not been reached, he added.

Encephalopathy was the most common grade 3 or greater adverse event related to axi-cel, occurring in 16% of patients, while increased alanine aminotransferase and decreased neutrophil count were each seen in 9% of patients, Dr. Neelapu said.

All 32 patients experienced CRS, including grade 3 CRS in 3 patients (9%), according to the reported data. Neurologic events were seen in 22 patients (69%) including grade 3 or greater in 8 (25%). There were 2 grade 4 neurologic events – both encephalopathies that resolved, according to Dr. Neelapu – and no grade 5 neurologic events.

ZUMA-12 is sponsored by Kite, a Gilead Company. Dr. Neelapu reported disclosures related to Acerta, Adicet Bio, Bristol-Myers Squibb, Kite, and various other pharmaceutical and biotechnology companies.
 

SOURCE: Neelapu SS et al. ASH 2020, Abstract 405.

Axicabtagene ciloleucel (axi-cel) can be safely administered and has substantial clinical benefit as part of first-line therapy in patients with high-risk large B-cell lymphoma, according to an investigator in a phase 2 study.

The chimeric antigen receptor (CAR) T-cell therapy had a “very high” overall response rate (ORR) of 85% and a complete response (CR) rate of 74% in the ZUMA-12 study, said investigator Sattva S. Neelapu, MD, of The University of Texas MD Anderson Cancer Center in Houston.

Nearly three-quarters of responses were ongoing with a median of follow-up of about 9 months, Dr. Neelapu said in interim analysis of ZUMA-12 presented at the annual meeting of the American Society of Hematology, which was held virtually.

While axi-cel is approved for treatment of certain relapsed/refractory large B-cell lymphomas (LBCLs), Dr. Neelapu said this is the first-ever study evaluating a CAR T-cell therapy as a first-line treatment for patients with LBCL that is high risk as defined by histology or International Prognostic Index (IPI) scoring.

Treatment with axi-cel was guided by dynamic risk assessment, Dr. Neelapu explained, meaning that patients received the CAR T-cell treatment if they had a positive interim positron emission tomography (PET) scan after two cycles of an anti-CD20 monoclonal antibody and anthracycline-containing regimen.
 

Longer follow-up needed

The interim efficacy analysis is based on 27 evaluable patients out of 40 patients planned to be enrolled, meaning that the final analysis is needed, and longer follow-up is needed to ensure that durability is maintained, Dr. Neelapu said in a question-and-answer session following his presentation.

Nevertheless, the 74% complete response rate in the frontline setting is “quite encouraging” compared to historical data in high-risk LBCL, where CR rates have generally been less than 50%, Dr. Neelapu added.

“Assuming that long-term data in the final analysis confirms this encouraging activity, I think we likely would need a randomized phase 3 trial to compare (axi-cel) head-to-head with frontline therapy,” he said.

Without mature data available, it’s hard to say in this single-arm study how much axi-cel is improving outcomes at the cost of significant toxicity, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

Adverse events as reported by Dr. Neelapu included grade 3 cytokine release syndrome (CRS) in 9% of patients, and 25% grade 3 or greater neurologic events in 25%.

“It appears as though it may be salvaging some patients, as the response rate is higher than that expected for chemotherapy alone in this setting,” Dr. Diefenbach said in an interview, “but toxicity is not trivial, so the long-term data will provide better clarity as to the degree of benefit.”
 

Ongoing responses at 9 months

The phase 2 ZUMA-12 study includes patients classified as high risk based on MYC and BCL2 and/or BCL6 translocations, or by an International Prognostic Indicator score of 3 or greater.

Patients initially received two cycles of anti-CD20 monoclonal antibody therapy plus an anthracycline containing regimen. Those with a positive interim PET (score of 4 or 5 on the 5-point Deauville scale) received fludarabine/cyclophosphamide conditioning plus axi-cel as a single intravenous infusion of 2 x 106 CAR T cells per kg of body weight.

As of the report at the ASH meeting, 32 patient had received axi-cel, of whom 32 were evaluable for safety and 27 were evaluable for efficacy.

The ORR was 85% (23 of 27 patients), and the CR rate was 74% (20 of 27 patients), Dr. Neelapu reported, noting that with a median follow-up of 9.3 months, 70% of responders (19 of 27) were in ongoing response.

Median duration of response, progression-free survival, and overall survival have not been reached, he added.

Encephalopathy was the most common grade 3 or greater adverse event related to axi-cel, occurring in 16% of patients, while increased alanine aminotransferase and decreased neutrophil count were each seen in 9% of patients, Dr. Neelapu said.

All 32 patients experienced CRS, including grade 3 CRS in 3 patients (9%), according to the reported data. Neurologic events were seen in 22 patients (69%) including grade 3 or greater in 8 (25%). There were 2 grade 4 neurologic events – both encephalopathies that resolved, according to Dr. Neelapu – and no grade 5 neurologic events.

ZUMA-12 is sponsored by Kite, a Gilead Company. Dr. Neelapu reported disclosures related to Acerta, Adicet Bio, Bristol-Myers Squibb, Kite, and various other pharmaceutical and biotechnology companies.
 

SOURCE: Neelapu SS et al. ASH 2020, Abstract 405.

The novel bispecific antibody odronextamab (REGN1979) is demonstrating encouraging activity, durable responses, and acceptable safety in a phase 1 study of patients with highly refractory B-cell non-Hodgkin lymphoma, according to an investigator.

Durable complete responses (CRs) to odronextamab are being observed in more than 80% of heavily pretreated patients with follicular lymphoma (FL) in the ongoing study, said Rajat Bannerji, MD, PhD, of Rutgers Cancer Institute of New Jersey, New Brunswick.

Likewise, durable CRs were seen in greater than 80% of patients diffuse large B-cell lymphoma (DLBCL) not previously exposed to chimeric antigen receptor (CAR) T-cell therapy, and also in about 20% of patients who were treated with CAR T cells, Dr. Bannerji reported at the annual meeting of the American Society of Hematology, held virtually this year.

For these patients with FL or DLBCL in the phase 1 study, cytokine release syndrome (CRS) and neurotoxicity events did not exceed grade 3 in severity, and no cases of tumor lysis syndrome (TLS) were observed, Dr. Bannerji added in his presentation.

Those findings suggest odronextamab, which binds to CD3 on T cells and CD20 on malignant B cells, may offer an “off-the-shelf, primarily outpatient treatment option” for patients with relapsed or refractory B-cell NHL, he said in concluding remarks on the study.

This first-in-human study took a conservative approach, according to Dr. Bannerji, by mandating hospital admission during an initial step-up dosing schedule used along with dexamethasone to mitigate risk of CRS.

“With our step-up dosing and steroid premedication, we really have not seen too many cytokine release issues, and I do think that in the future it would be safe even to do step-up in the majority of patients as an outpatient,” he said in a discussion following his presentation.
 

Durability with further follow-up

Phase 1 data for odronextamab reported by Dr. Bannerji at the 2019 ASH meeting showed encouraging safety, tolerability, and preliminary efficacy in patients with relapsed or refractory B-cell NHL at doses up to 320 mg weekly.

In the presentation at this year’s ASH meeting, Dr. Bannerji provided updated safety and efficacy results, including longer follow-up for duration of response.

In patients with relapsed/refractory FL, the overall response rate (ORR) was 90% (27 of 30 patients), including a CR rate of 70% (21 of 30 patients), it was reported at ASH 2020. The median duration of complete response (DoCR) was not reached, with 81% of CRs durable and ongoing for up to 41 months, according to Dr. Bannerji.

In patients with relapsed/refractory DLBCL who had not received prior CAR T-cell therapy, the ORR was 55% (6 of 11 patients), all of which were complete responses, data show. The median DoCR was again not reached, with 83% of CRs durable and ongoing for up to 21 months as of this report.

In a larger group of patients with relapsed/refractory DLBCL who had received CAR T-cell therapy, the ORR was 33% (8 of 24 patients) including a 21% CR rate (5 of 24 patients). Median DoCR was not reached, the study data show, with 100% of these CRs ongoing for up to 20 months.

Odronextamab was given up to 320 mg weekly with no dose-limiting toxicities and the maximum tolerated dose not reached, according to Dr. Bannerji, who noted that no patients had discontinued treatment because of CRS or neurotoxicity.

Cytokine release syndrome was seen in about 35% of patients with DLBCL, FL, or other B-cell NHLs (48 of 136 patients), and most cases were grade 1 or 2 in severity. No FL or DLBCL patients experienced CRS higher than grade 3, according to the investigator, who reported one case of grade 3 CRS occurring out of 38 FL patients (about 3%) and four cases of grade 3 CRS out of 78 total DLBCL patients (about 5%).

No patients with FL experienced immune effector cell-associated neurotoxicity syndrome (ICANS)-like events of grade 3 or greater, the investigator said. Three cases of grade 3 ICANS-like events were reported among DLBCL patients: two cases that occurred during the step-up dosing phase and one that occurred at full dose.

No TLS events of grade 3 or greater were observed in any FL or DLBCL patients, he added.
 

More research needed

Although efficacy and safety results from this phase 1 study of odronextamab are encouraging, the durability, combinability, and potential for sequencing of bispecific antibodies deserves further investigation, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

“Bispecifics in lymphoma as a class are extremely promising,” Dr. Diefenbach said in an interview. “They’re highly active and they activate an immune response against the tumor without inducing, for the most part, the same degree of neurotoxicity and CRS most CAR T cells do.

“I think the challenge is going to be to figure out how to give them in combination with other therapies to maximize durability, and how to sequence bispecifics and CAR T cells,” she added.

A global phase 2 trial of odronextamab in patients with relapsed or refractory B-cell NHL is currently recruiting. According to Dr. Bannerji, further studies are planned to evaluate odronextamab with chemotherapy and in chemotherapy-free combinations in earlier lines of treatment.

The study is sponsored by Regeneron Pharmaceuticals. Dr. Bannerji reported research funding from Regeneron, AbbVie, F. Hoffmann La Roche Ltd/Genentech Inc., and Pharmacyclics LLC, an AbbVie company. Dr. Bannerji’s spouse is an employee of Sanofi Pasteur.
 

SOURCE: Bannerji R et al. ASH 2020, Abstract 400.

The novel bispecific antibody odronextamab (REGN1979) is demonstrating encouraging activity, durable responses, and acceptable safety in a phase 1 study of patients with highly refractory B-cell non-Hodgkin lymphoma, according to an investigator.

Durable complete responses (CRs) to odronextamab are being observed in more than 80% of heavily pretreated patients with follicular lymphoma (FL) in the ongoing study, said Rajat Bannerji, MD, PhD, of Rutgers Cancer Institute of New Jersey, New Brunswick.

Likewise, durable CRs were seen in greater than 80% of patients diffuse large B-cell lymphoma (DLBCL) not previously exposed to chimeric antigen receptor (CAR) T-cell therapy, and also in about 20% of patients who were treated with CAR T cells, Dr. Bannerji reported at the annual meeting of the American Society of Hematology, held virtually this year.

For these patients with FL or DLBCL in the phase 1 study, cytokine release syndrome (CRS) and neurotoxicity events did not exceed grade 3 in severity, and no cases of tumor lysis syndrome (TLS) were observed, Dr. Bannerji added in his presentation.

Those findings suggest odronextamab, which binds to CD3 on T cells and CD20 on malignant B cells, may offer an “off-the-shelf, primarily outpatient treatment option” for patients with relapsed or refractory B-cell NHL, he said in concluding remarks on the study.

This first-in-human study took a conservative approach, according to Dr. Bannerji, by mandating hospital admission during an initial step-up dosing schedule used along with dexamethasone to mitigate risk of CRS.

“With our step-up dosing and steroid premedication, we really have not seen too many cytokine release issues, and I do think that in the future it would be safe even to do step-up in the majority of patients as an outpatient,” he said in a discussion following his presentation.
 

Durability with further follow-up

Phase 1 data for odronextamab reported by Dr. Bannerji at the 2019 ASH meeting showed encouraging safety, tolerability, and preliminary efficacy in patients with relapsed or refractory B-cell NHL at doses up to 320 mg weekly.

In the presentation at this year’s ASH meeting, Dr. Bannerji provided updated safety and efficacy results, including longer follow-up for duration of response.

In patients with relapsed/refractory FL, the overall response rate (ORR) was 90% (27 of 30 patients), including a CR rate of 70% (21 of 30 patients), it was reported at ASH 2020. The median duration of complete response (DoCR) was not reached, with 81% of CRs durable and ongoing for up to 41 months, according to Dr. Bannerji.

In patients with relapsed/refractory DLBCL who had not received prior CAR T-cell therapy, the ORR was 55% (6 of 11 patients), all of which were complete responses, data show. The median DoCR was again not reached, with 83% of CRs durable and ongoing for up to 21 months as of this report.

In a larger group of patients with relapsed/refractory DLBCL who had received CAR T-cell therapy, the ORR was 33% (8 of 24 patients) including a 21% CR rate (5 of 24 patients). Median DoCR was not reached, the study data show, with 100% of these CRs ongoing for up to 20 months.

Odronextamab was given up to 320 mg weekly with no dose-limiting toxicities and the maximum tolerated dose not reached, according to Dr. Bannerji, who noted that no patients had discontinued treatment because of CRS or neurotoxicity.

Cytokine release syndrome was seen in about 35% of patients with DLBCL, FL, or other B-cell NHLs (48 of 136 patients), and most cases were grade 1 or 2 in severity. No FL or DLBCL patients experienced CRS higher than grade 3, according to the investigator, who reported one case of grade 3 CRS occurring out of 38 FL patients (about 3%) and four cases of grade 3 CRS out of 78 total DLBCL patients (about 5%).

No patients with FL experienced immune effector cell-associated neurotoxicity syndrome (ICANS)-like events of grade 3 or greater, the investigator said. Three cases of grade 3 ICANS-like events were reported among DLBCL patients: two cases that occurred during the step-up dosing phase and one that occurred at full dose.

No TLS events of grade 3 or greater were observed in any FL or DLBCL patients, he added.
 

More research needed

Although efficacy and safety results from this phase 1 study of odronextamab are encouraging, the durability, combinability, and potential for sequencing of bispecific antibodies deserves further investigation, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

“Bispecifics in lymphoma as a class are extremely promising,” Dr. Diefenbach said in an interview. “They’re highly active and they activate an immune response against the tumor without inducing, for the most part, the same degree of neurotoxicity and CRS most CAR T cells do.

“I think the challenge is going to be to figure out how to give them in combination with other therapies to maximize durability, and how to sequence bispecifics and CAR T cells,” she added.

A global phase 2 trial of odronextamab in patients with relapsed or refractory B-cell NHL is currently recruiting. According to Dr. Bannerji, further studies are planned to evaluate odronextamab with chemotherapy and in chemotherapy-free combinations in earlier lines of treatment.

The study is sponsored by Regeneron Pharmaceuticals. Dr. Bannerji reported research funding from Regeneron, AbbVie, F. Hoffmann La Roche Ltd/Genentech Inc., and Pharmacyclics LLC, an AbbVie company. Dr. Bannerji’s spouse is an employee of Sanofi Pasteur.
 

SOURCE: Bannerji R et al. ASH 2020, Abstract 400.

The novel bispecific antibody odronextamab (REGN1979) is demonstrating encouraging activity, durable responses, and acceptable safety in a phase 1 study of patients with highly refractory B-cell non-Hodgkin lymphoma, according to an investigator.

Durable complete responses (CRs) to odronextamab are being observed in more than 80% of heavily pretreated patients with follicular lymphoma (FL) in the ongoing study, said Rajat Bannerji, MD, PhD, of Rutgers Cancer Institute of New Jersey, New Brunswick.

Likewise, durable CRs were seen in greater than 80% of patients diffuse large B-cell lymphoma (DLBCL) not previously exposed to chimeric antigen receptor (CAR) T-cell therapy, and also in about 20% of patients who were treated with CAR T cells, Dr. Bannerji reported at the annual meeting of the American Society of Hematology, held virtually this year.

For these patients with FL or DLBCL in the phase 1 study, cytokine release syndrome (CRS) and neurotoxicity events did not exceed grade 3 in severity, and no cases of tumor lysis syndrome (TLS) were observed, Dr. Bannerji added in his presentation.

Those findings suggest odronextamab, which binds to CD3 on T cells and CD20 on malignant B cells, may offer an “off-the-shelf, primarily outpatient treatment option” for patients with relapsed or refractory B-cell NHL, he said in concluding remarks on the study.

This first-in-human study took a conservative approach, according to Dr. Bannerji, by mandating hospital admission during an initial step-up dosing schedule used along with dexamethasone to mitigate risk of CRS.

“With our step-up dosing and steroid premedication, we really have not seen too many cytokine release issues, and I do think that in the future it would be safe even to do step-up in the majority of patients as an outpatient,” he said in a discussion following his presentation.
 

Durability with further follow-up

Phase 1 data for odronextamab reported by Dr. Bannerji at the 2019 ASH meeting showed encouraging safety, tolerability, and preliminary efficacy in patients with relapsed or refractory B-cell NHL at doses up to 320 mg weekly.

In the presentation at this year’s ASH meeting, Dr. Bannerji provided updated safety and efficacy results, including longer follow-up for duration of response.

In patients with relapsed/refractory FL, the overall response rate (ORR) was 90% (27 of 30 patients), including a CR rate of 70% (21 of 30 patients), it was reported at ASH 2020. The median duration of complete response (DoCR) was not reached, with 81% of CRs durable and ongoing for up to 41 months, according to Dr. Bannerji.

In patients with relapsed/refractory DLBCL who had not received prior CAR T-cell therapy, the ORR was 55% (6 of 11 patients), all of which were complete responses, data show. The median DoCR was again not reached, with 83% of CRs durable and ongoing for up to 21 months as of this report.

In a larger group of patients with relapsed/refractory DLBCL who had received CAR T-cell therapy, the ORR was 33% (8 of 24 patients) including a 21% CR rate (5 of 24 patients). Median DoCR was not reached, the study data show, with 100% of these CRs ongoing for up to 20 months.

Odronextamab was given up to 320 mg weekly with no dose-limiting toxicities and the maximum tolerated dose not reached, according to Dr. Bannerji, who noted that no patients had discontinued treatment because of CRS or neurotoxicity.

Cytokine release syndrome was seen in about 35% of patients with DLBCL, FL, or other B-cell NHLs (48 of 136 patients), and most cases were grade 1 or 2 in severity. No FL or DLBCL patients experienced CRS higher than grade 3, according to the investigator, who reported one case of grade 3 CRS occurring out of 38 FL patients (about 3%) and four cases of grade 3 CRS out of 78 total DLBCL patients (about 5%).

No patients with FL experienced immune effector cell-associated neurotoxicity syndrome (ICANS)-like events of grade 3 or greater, the investigator said. Three cases of grade 3 ICANS-like events were reported among DLBCL patients: two cases that occurred during the step-up dosing phase and one that occurred at full dose.

No TLS events of grade 3 or greater were observed in any FL or DLBCL patients, he added.
 

More research needed

Although efficacy and safety results from this phase 1 study of odronextamab are encouraging, the durability, combinability, and potential for sequencing of bispecific antibodies deserves further investigation, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

“Bispecifics in lymphoma as a class are extremely promising,” Dr. Diefenbach said in an interview. “They’re highly active and they activate an immune response against the tumor without inducing, for the most part, the same degree of neurotoxicity and CRS most CAR T cells do.

“I think the challenge is going to be to figure out how to give them in combination with other therapies to maximize durability, and how to sequence bispecifics and CAR T cells,” she added.

A global phase 2 trial of odronextamab in patients with relapsed or refractory B-cell NHL is currently recruiting. According to Dr. Bannerji, further studies are planned to evaluate odronextamab with chemotherapy and in chemotherapy-free combinations in earlier lines of treatment.

The study is sponsored by Regeneron Pharmaceuticals. Dr. Bannerji reported research funding from Regeneron, AbbVie, F. Hoffmann La Roche Ltd/Genentech Inc., and Pharmacyclics LLC, an AbbVie company. Dr. Bannerji’s spouse is an employee of Sanofi Pasteur.
 

SOURCE: Bannerji R et al. ASH 2020, Abstract 400.