Guselkumab induction improves moderate to severe active UC at week 12

Guselkumab induction therapy appears to improve key clinical, histologic, and endoscopic outcomes in patients with moderately to severely active ulcerative colitis (UC) at week 12, according to findings presented at the annual meeting of the American College of Gastroenterology.

The efficacy of the 200-mg dose and the 400-mg dose was comparable, said David Rubin, MD, a gastroenterologist at the University of Chicago Medicine Inflammatory Bowel Disease Center. Outcomes improved in all patients, with or without a history of inadequate response or intolerance to advanced therapy.

Guselkumab, an interleukin-12 p19 subunit antagonist, is currently being investigated in inflammatory bowel disease.

The QUASAR Induction Study 1 (NCT04033445) is a phase 2b, randomized, double-blind, placebo-controlled study that evaluates guselkumab as induction therapy in patients with moderately to severely active UC. Inclusion criteria specify a demonstrated inadequate response or intolerance to conventional therapy, such as thiopurines or corticosteroids, or to advanced therapy, such as tumor necrosis factor–alpha antagonists, vedolizumab, or tofacitinib. The study didn’t include patients exposed to ustekinumab.

Study participants were age 18 and older with moderately to severely active UC, defined as a modified Mayo score of 5-9 with a Mayo rectal bleeding subscore of 1 or greater and a Mayo endoscopy subscore of 2 or greater at baseline. The groups were randomized 1:1:1 to receive 400 mg of IV guselkumab, 200 mg of guselkumab, or placebo at weeks 0, 4, and 8.

At week 12, the research team looked for several key endpoints. Clinical response was defined as a modified Mayo score decrease of 30% or more and a drop in 2 or more points, with either a 1-point decrease or more in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.

Clinical remission was defined as a stool frequency subscore of 0 or 1 that hadn’t increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.

In addition, symptomatic remission was defined as a stool subscore of 0 or 1 that hadn’t increased from baseline and rectal bleeding subscore of 0.

Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic normalization was an endoscopy subscore of 0.

Notably, the research team looked at histoendoscopic mucosal improvement, which includes a combination of endoscopic improvement and histologic improvement (neutrophil infiltration in less than 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue, according to the Geboes grading system).

Among the 313 total patients, 47% had a history of inadequate response or intolerance to advanced therapy, and about half of these patients had prior inadequate response or intolerance to two or more advanced therapy classes.

At baseline, about 90% of patients had an endoscopic subscore of 3 (severe). More than half had extensive UC, and the average UC duration was 9 years. About 20% overall had extraintestinal manifestations present, which were noted in 33% of the 400 mg guselkumab treatment arm.

At week 12, clinical response was achieved by a higher proportion of patients treated with guselkumab versus placebo, at 50.5% versus 25.5% for patients with prior inadequate response or intolerance to advanced therapy and 70.3% versus 29.6% for those without prior inadequate response or intolerance to advanced therapy, the authors reported in the abstract.

Compared with placebo, higher proportions of patients treated with guselkumab achieved clinical, endoscopic, and histologic outcomes in both groups with or without inadequate response or intolerance to advanced therapy. Generally, those without a history of inadequate response had higher response rates across all endpoints.

Overall, both the 200-mg and 400-mg doses of guselkumab were statistically superior to the placebo across all endpoints for both groups (with or without inadequate response or intolerance). Although the efficacy was comparable for the two doses, the 400-mg dose was associated with greater histoendoscopic mucosal improvement in both groups.

“It’s of interest to think about how we position and sequence our therapies with this additional data,” Dr. Rubin said.

The study was sponsored by Janssen Research & Development. Several authors are employees for and have stock options with Johnson & Johnson and Janssen. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Janssen.

Guselkumab induction therapy appears to improve key clinical, histologic, and endoscopic outcomes in patients with moderately to severely active ulcerative colitis (UC) at week 12, according to findings presented at the annual meeting of the American College of Gastroenterology.

The efficacy of the 200-mg dose and the 400-mg dose was comparable, said David Rubin, MD, a gastroenterologist at the University of Chicago Medicine Inflammatory Bowel Disease Center. Outcomes improved in all patients, with or without a history of inadequate response or intolerance to advanced therapy.

Guselkumab, an interleukin-12 p19 subunit antagonist, is currently being investigated in inflammatory bowel disease.

The QUASAR Induction Study 1 (NCT04033445) is a phase 2b, randomized, double-blind, placebo-controlled study that evaluates guselkumab as induction therapy in patients with moderately to severely active UC. Inclusion criteria specify a demonstrated inadequate response or intolerance to conventional therapy, such as thiopurines or corticosteroids, or to advanced therapy, such as tumor necrosis factor–alpha antagonists, vedolizumab, or tofacitinib. The study didn’t include patients exposed to ustekinumab.

Study participants were age 18 and older with moderately to severely active UC, defined as a modified Mayo score of 5-9 with a Mayo rectal bleeding subscore of 1 or greater and a Mayo endoscopy subscore of 2 or greater at baseline. The groups were randomized 1:1:1 to receive 400 mg of IV guselkumab, 200 mg of guselkumab, or placebo at weeks 0, 4, and 8.

At week 12, the research team looked for several key endpoints. Clinical response was defined as a modified Mayo score decrease of 30% or more and a drop in 2 or more points, with either a 1-point decrease or more in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.

Clinical remission was defined as a stool frequency subscore of 0 or 1 that hadn’t increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.

In addition, symptomatic remission was defined as a stool subscore of 0 or 1 that hadn’t increased from baseline and rectal bleeding subscore of 0.

Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic normalization was an endoscopy subscore of 0.

Notably, the research team looked at histoendoscopic mucosal improvement, which includes a combination of endoscopic improvement and histologic improvement (neutrophil infiltration in less than 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue, according to the Geboes grading system).

Among the 313 total patients, 47% had a history of inadequate response or intolerance to advanced therapy, and about half of these patients had prior inadequate response or intolerance to two or more advanced therapy classes.

At baseline, about 90% of patients had an endoscopic subscore of 3 (severe). More than half had extensive UC, and the average UC duration was 9 years. About 20% overall had extraintestinal manifestations present, which were noted in 33% of the 400 mg guselkumab treatment arm.

At week 12, clinical response was achieved by a higher proportion of patients treated with guselkumab versus placebo, at 50.5% versus 25.5% for patients with prior inadequate response or intolerance to advanced therapy and 70.3% versus 29.6% for those without prior inadequate response or intolerance to advanced therapy, the authors reported in the abstract.

Compared with placebo, higher proportions of patients treated with guselkumab achieved clinical, endoscopic, and histologic outcomes in both groups with or without inadequate response or intolerance to advanced therapy. Generally, those without a history of inadequate response had higher response rates across all endpoints.

Overall, both the 200-mg and 400-mg doses of guselkumab were statistically superior to the placebo across all endpoints for both groups (with or without inadequate response or intolerance). Although the efficacy was comparable for the two doses, the 400-mg dose was associated with greater histoendoscopic mucosal improvement in both groups.

“It’s of interest to think about how we position and sequence our therapies with this additional data,” Dr. Rubin said.

The study was sponsored by Janssen Research & Development. Several authors are employees for and have stock options with Johnson & Johnson and Janssen. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Janssen.

Guselkumab induction therapy appears to improve key clinical, histologic, and endoscopic outcomes in patients with moderately to severely active ulcerative colitis (UC) at week 12, according to findings presented at the annual meeting of the American College of Gastroenterology.

The efficacy of the 200-mg dose and the 400-mg dose was comparable, said David Rubin, MD, a gastroenterologist at the University of Chicago Medicine Inflammatory Bowel Disease Center. Outcomes improved in all patients, with or without a history of inadequate response or intolerance to advanced therapy.

Guselkumab, an interleukin-12 p19 subunit antagonist, is currently being investigated in inflammatory bowel disease.

The QUASAR Induction Study 1 (NCT04033445) is a phase 2b, randomized, double-blind, placebo-controlled study that evaluates guselkumab as induction therapy in patients with moderately to severely active UC. Inclusion criteria specify a demonstrated inadequate response or intolerance to conventional therapy, such as thiopurines or corticosteroids, or to advanced therapy, such as tumor necrosis factor–alpha antagonists, vedolizumab, or tofacitinib. The study didn’t include patients exposed to ustekinumab.

Study participants were age 18 and older with moderately to severely active UC, defined as a modified Mayo score of 5-9 with a Mayo rectal bleeding subscore of 1 or greater and a Mayo endoscopy subscore of 2 or greater at baseline. The groups were randomized 1:1:1 to receive 400 mg of IV guselkumab, 200 mg of guselkumab, or placebo at weeks 0, 4, and 8.

At week 12, the research team looked for several key endpoints. Clinical response was defined as a modified Mayo score decrease of 30% or more and a drop in 2 or more points, with either a 1-point decrease or more in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.

Clinical remission was defined as a stool frequency subscore of 0 or 1 that hadn’t increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.

In addition, symptomatic remission was defined as a stool subscore of 0 or 1 that hadn’t increased from baseline and rectal bleeding subscore of 0.

Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic normalization was an endoscopy subscore of 0.

Notably, the research team looked at histoendoscopic mucosal improvement, which includes a combination of endoscopic improvement and histologic improvement (neutrophil infiltration in less than 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue, according to the Geboes grading system).

Among the 313 total patients, 47% had a history of inadequate response or intolerance to advanced therapy, and about half of these patients had prior inadequate response or intolerance to two or more advanced therapy classes.

At baseline, about 90% of patients had an endoscopic subscore of 3 (severe). More than half had extensive UC, and the average UC duration was 9 years. About 20% overall had extraintestinal manifestations present, which were noted in 33% of the 400 mg guselkumab treatment arm.

At week 12, clinical response was achieved by a higher proportion of patients treated with guselkumab versus placebo, at 50.5% versus 25.5% for patients with prior inadequate response or intolerance to advanced therapy and 70.3% versus 29.6% for those without prior inadequate response or intolerance to advanced therapy, the authors reported in the abstract.

Compared with placebo, higher proportions of patients treated with guselkumab achieved clinical, endoscopic, and histologic outcomes in both groups with or without inadequate response or intolerance to advanced therapy. Generally, those without a history of inadequate response had higher response rates across all endpoints.

Overall, both the 200-mg and 400-mg doses of guselkumab were statistically superior to the placebo across all endpoints for both groups (with or without inadequate response or intolerance). Although the efficacy was comparable for the two doses, the 400-mg dose was associated with greater histoendoscopic mucosal improvement in both groups.

“It’s of interest to think about how we position and sequence our therapies with this additional data,” Dr. Rubin said.

The study was sponsored by Janssen Research & Development. Several authors are employees for and have stock options with Johnson & Johnson and Janssen. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Janssen.