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WASHINGTON —
The primary outcome of clinical remission at 44 weeks was greater with either of two dose regimens of guselkumab than with placebo, David Rubin, MD, AGAF, reported as part of his presentation (Abstract 759) at the annual Digestive Disease Week® (DDW).
Guselkumab is not the only biologic approved or in development for UC, but it is unique because of its dual action. It is an interleukin (IL)-23p19 subunit inhibitor that blocks IL-23 and also binds to the CD64 receptor on cells that produce IL-23.
Dr. Rubin, who is chief of the Section of Gastroenterology, Hepatology and Nutrition at University of Chicago Medicine, Chicago, said he was unsure at the beginning of the trial if this dual activity “might have any value.”
Targeting both the IL-23 circulating in the tissue and the receptor remains to be proven, “but nonetheless seems reasonable,” he said.
The study included 568 people, about 42% of whom had an inadequate response or were intolerant to prior advanced therapy, and 42.5% of whom had failed two or more advanced therapy classes.
Clinical responders from two prior guselkumab induction studies were enrolled in this randomized withdrawal, double-blind maintenance trial. At either 12 weeks or 24 weeks of induction, patients were randomly assigned to subcutaneous 200-mg guselkumab every 4 weeks (n = 190), 100-mg guselkumab every 8 weeks (n = 188), or placebo (n = 190). The placebo group served as a guselkumab withdrawal group.
Participants had a mean age of 41 years and a mean disease duration of 7.8 years. The 40% using oral corticosteroids were tapered off during the study.
A total of 45.2% of the 100-mg guselkumab group and 50.0% of the 200-mg guselkumab group met the primary outcome of clinical remission at week 44 compared with 18.9% with placebo.
“It was interesting to note that the 200 mg every 4 weeks was similar in efficacy at week 44 to the 100 mg every 8 weeks. It’s much less medicine, but you get similar results,” Dr. Rubin said.
Secondary Outcomes Also Superior
“The bottom line is not only did it work, but it worked when you look at some secondary endpoints, including endoscopic remission, where the bowel is completely healed,” Dr. Rubin said in an interview.
Overall, 34% of all participants who received guselkumab achieved this outcome, “which is a very high rate,” he said. “We haven’t seen a Mayo score of zero — meaning endoscopic remission — at that rate with any of our other therapies currently.”
Among the participants who achieved clinical remission, 69% of them also showed complete remission on endoscopy.
Other secondary outcomes significantly better at week 44 vs placebo included corticosteroid-free clinical remission, maintenance of clinical remission, clinical response, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, endoscopic normalization, Inflammatory Bowel Disease Questionnaire remission, and fatigue response.
“It was a great study. I think it’s very promising data,” said session co-moderator Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston.
“As we get more data from these more selective interleukins, we’ll get a better sense of how that plays out” vs other similar agents in development, he added.
IL-23 Target Seems Safe
One or more adverse events were reported by 70% of the higher-dose guselkumab group, 65% of the lower-dose guselkumab group, and 68% of the placebo group.
The most common adverse events in a combined 200-mg and 100-mg guselkumab group were lower than in the placebo group: 11.2% vs 14.1% reported COVID-19, 11.2% vs 29.7% reported exacerbation of UC, and 6.1% vs 6.8% experienced arthralgia, respectively.
No cases of active tuberculosis, opportunistic infection, anaphylaxis, serum sickness, Hy’s law, or serious hepatic issues were reported. One patient had clear cell renal carcinoma, another had rectal adenocarcinoma, and one hemorrhagic stroke was reported in the treatment groups. No patients died during the trial.
A higher proportion of people in the placebo group (13.7%) discontinued the study than those in the 100-mg guselkumab group (10.6%) and the 200-mg guselkumab group (11.6%).
“In general, we have accepted that the IL-23 target seems to be a very safe one,” Dr. Rubin said.
A leading theory is that unlike some interleukins, IL-23 is only expressed where the body has inflammation; therefore, targeting IL-23 does not affect other areas, he explained.
If approved by the Food and Drug Administration, it would expand the official indications for guselkumab, which was approved in 2020 for psoriatic arthritis and in 2017 for plaque psoriasis.
The study was supported by Janssen Research & Development, LLC. Dr. Rubin is a consultant for Janssen. Dr. Ananthakrishnan had no relevant disclosures.
A version of this article appeared on Medscape.com.
WASHINGTON —
The primary outcome of clinical remission at 44 weeks was greater with either of two dose regimens of guselkumab than with placebo, David Rubin, MD, AGAF, reported as part of his presentation (Abstract 759) at the annual Digestive Disease Week® (DDW).
Guselkumab is not the only biologic approved or in development for UC, but it is unique because of its dual action. It is an interleukin (IL)-23p19 subunit inhibitor that blocks IL-23 and also binds to the CD64 receptor on cells that produce IL-23.
Dr. Rubin, who is chief of the Section of Gastroenterology, Hepatology and Nutrition at University of Chicago Medicine, Chicago, said he was unsure at the beginning of the trial if this dual activity “might have any value.”
Targeting both the IL-23 circulating in the tissue and the receptor remains to be proven, “but nonetheless seems reasonable,” he said.
The study included 568 people, about 42% of whom had an inadequate response or were intolerant to prior advanced therapy, and 42.5% of whom had failed two or more advanced therapy classes.
Clinical responders from two prior guselkumab induction studies were enrolled in this randomized withdrawal, double-blind maintenance trial. At either 12 weeks or 24 weeks of induction, patients were randomly assigned to subcutaneous 200-mg guselkumab every 4 weeks (n = 190), 100-mg guselkumab every 8 weeks (n = 188), or placebo (n = 190). The placebo group served as a guselkumab withdrawal group.
Participants had a mean age of 41 years and a mean disease duration of 7.8 years. The 40% using oral corticosteroids were tapered off during the study.
A total of 45.2% of the 100-mg guselkumab group and 50.0% of the 200-mg guselkumab group met the primary outcome of clinical remission at week 44 compared with 18.9% with placebo.
“It was interesting to note that the 200 mg every 4 weeks was similar in efficacy at week 44 to the 100 mg every 8 weeks. It’s much less medicine, but you get similar results,” Dr. Rubin said.
Secondary Outcomes Also Superior
“The bottom line is not only did it work, but it worked when you look at some secondary endpoints, including endoscopic remission, where the bowel is completely healed,” Dr. Rubin said in an interview.
Overall, 34% of all participants who received guselkumab achieved this outcome, “which is a very high rate,” he said. “We haven’t seen a Mayo score of zero — meaning endoscopic remission — at that rate with any of our other therapies currently.”
Among the participants who achieved clinical remission, 69% of them also showed complete remission on endoscopy.
Other secondary outcomes significantly better at week 44 vs placebo included corticosteroid-free clinical remission, maintenance of clinical remission, clinical response, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, endoscopic normalization, Inflammatory Bowel Disease Questionnaire remission, and fatigue response.
“It was a great study. I think it’s very promising data,” said session co-moderator Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston.
“As we get more data from these more selective interleukins, we’ll get a better sense of how that plays out” vs other similar agents in development, he added.
IL-23 Target Seems Safe
One or more adverse events were reported by 70% of the higher-dose guselkumab group, 65% of the lower-dose guselkumab group, and 68% of the placebo group.
The most common adverse events in a combined 200-mg and 100-mg guselkumab group were lower than in the placebo group: 11.2% vs 14.1% reported COVID-19, 11.2% vs 29.7% reported exacerbation of UC, and 6.1% vs 6.8% experienced arthralgia, respectively.
No cases of active tuberculosis, opportunistic infection, anaphylaxis, serum sickness, Hy’s law, or serious hepatic issues were reported. One patient had clear cell renal carcinoma, another had rectal adenocarcinoma, and one hemorrhagic stroke was reported in the treatment groups. No patients died during the trial.
A higher proportion of people in the placebo group (13.7%) discontinued the study than those in the 100-mg guselkumab group (10.6%) and the 200-mg guselkumab group (11.6%).
“In general, we have accepted that the IL-23 target seems to be a very safe one,” Dr. Rubin said.
A leading theory is that unlike some interleukins, IL-23 is only expressed where the body has inflammation; therefore, targeting IL-23 does not affect other areas, he explained.
If approved by the Food and Drug Administration, it would expand the official indications for guselkumab, which was approved in 2020 for psoriatic arthritis and in 2017 for plaque psoriasis.
The study was supported by Janssen Research & Development, LLC. Dr. Rubin is a consultant for Janssen. Dr. Ananthakrishnan had no relevant disclosures.
A version of this article appeared on Medscape.com.
WASHINGTON —
The primary outcome of clinical remission at 44 weeks was greater with either of two dose regimens of guselkumab than with placebo, David Rubin, MD, AGAF, reported as part of his presentation (Abstract 759) at the annual Digestive Disease Week® (DDW).
Guselkumab is not the only biologic approved or in development for UC, but it is unique because of its dual action. It is an interleukin (IL)-23p19 subunit inhibitor that blocks IL-23 and also binds to the CD64 receptor on cells that produce IL-23.
Dr. Rubin, who is chief of the Section of Gastroenterology, Hepatology and Nutrition at University of Chicago Medicine, Chicago, said he was unsure at the beginning of the trial if this dual activity “might have any value.”
Targeting both the IL-23 circulating in the tissue and the receptor remains to be proven, “but nonetheless seems reasonable,” he said.
The study included 568 people, about 42% of whom had an inadequate response or were intolerant to prior advanced therapy, and 42.5% of whom had failed two or more advanced therapy classes.
Clinical responders from two prior guselkumab induction studies were enrolled in this randomized withdrawal, double-blind maintenance trial. At either 12 weeks or 24 weeks of induction, patients were randomly assigned to subcutaneous 200-mg guselkumab every 4 weeks (n = 190), 100-mg guselkumab every 8 weeks (n = 188), or placebo (n = 190). The placebo group served as a guselkumab withdrawal group.
Participants had a mean age of 41 years and a mean disease duration of 7.8 years. The 40% using oral corticosteroids were tapered off during the study.
A total of 45.2% of the 100-mg guselkumab group and 50.0% of the 200-mg guselkumab group met the primary outcome of clinical remission at week 44 compared with 18.9% with placebo.
“It was interesting to note that the 200 mg every 4 weeks was similar in efficacy at week 44 to the 100 mg every 8 weeks. It’s much less medicine, but you get similar results,” Dr. Rubin said.
Secondary Outcomes Also Superior
“The bottom line is not only did it work, but it worked when you look at some secondary endpoints, including endoscopic remission, where the bowel is completely healed,” Dr. Rubin said in an interview.
Overall, 34% of all participants who received guselkumab achieved this outcome, “which is a very high rate,” he said. “We haven’t seen a Mayo score of zero — meaning endoscopic remission — at that rate with any of our other therapies currently.”
Among the participants who achieved clinical remission, 69% of them also showed complete remission on endoscopy.
Other secondary outcomes significantly better at week 44 vs placebo included corticosteroid-free clinical remission, maintenance of clinical remission, clinical response, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, endoscopic normalization, Inflammatory Bowel Disease Questionnaire remission, and fatigue response.
“It was a great study. I think it’s very promising data,” said session co-moderator Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston.
“As we get more data from these more selective interleukins, we’ll get a better sense of how that plays out” vs other similar agents in development, he added.
IL-23 Target Seems Safe
One or more adverse events were reported by 70% of the higher-dose guselkumab group, 65% of the lower-dose guselkumab group, and 68% of the placebo group.
The most common adverse events in a combined 200-mg and 100-mg guselkumab group were lower than in the placebo group: 11.2% vs 14.1% reported COVID-19, 11.2% vs 29.7% reported exacerbation of UC, and 6.1% vs 6.8% experienced arthralgia, respectively.
No cases of active tuberculosis, opportunistic infection, anaphylaxis, serum sickness, Hy’s law, or serious hepatic issues were reported. One patient had clear cell renal carcinoma, another had rectal adenocarcinoma, and one hemorrhagic stroke was reported in the treatment groups. No patients died during the trial.
A higher proportion of people in the placebo group (13.7%) discontinued the study than those in the 100-mg guselkumab group (10.6%) and the 200-mg guselkumab group (11.6%).
“In general, we have accepted that the IL-23 target seems to be a very safe one,” Dr. Rubin said.
A leading theory is that unlike some interleukins, IL-23 is only expressed where the body has inflammation; therefore, targeting IL-23 does not affect other areas, he explained.
If approved by the Food and Drug Administration, it would expand the official indications for guselkumab, which was approved in 2020 for psoriatic arthritis and in 2017 for plaque psoriasis.
The study was supported by Janssen Research & Development, LLC. Dr. Rubin is a consultant for Janssen. Dr. Ananthakrishnan had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM DDW 2024