Filgotinib 200 mg Safe, Effective for Moderate to Severe Ulcerative Colitis

By Lisa Rapaport

June 15, 2021

(Reuters Health) - A 200-mg dose of filgotinib helped significantly more patients with ulcerative colitis than placebo to achieve clinical remission in a trial among individuals with and without prior treatment with biologics, according to a new study.

The randomized, double-blind placebo-controlled trial enrolled 659 patients with ulcerative colitis who had inadequate response, lost response, or intolerance to corticosteroids or immunosuppressants (biologic naive) as well as 689 patients who had inadequate response, lost response, or intolerance to tumor necrosis factor (TNF) antagonists or vedolizumab. Participants were randomized 2:2:1 to receive oral filgotinib 100 mg, 200 mg, or placebo once daily for 11 weeks for an induction study.

At week 10, a significantly greater proportion of patients on filgotinib 200 mg achieved clinical remission than with placebo among both biologic-naive (26.1% vs 15.3%) and biologic-experienced participants (11.5% v 4.2%). Clinical remission wasn't statistically significant at week 10 for filgotinib 100 mg, however.

Adverse events at week 10 were similar with filgotinib 200 mg (4.3%), filgotinib 100 mg (5.0%), and placebo (4.7%).

"Every drug has dose-response relationship, and at a certain threshold they are optimally effective in blocking their target, without too much toxicity," said Dr. Siddharth Singh, director of the IBD Center and an assistant professor of medicine at the University of California, San Diego, who coauthored a commentary accompanying the study.

"For filgotinib, for ulcerative colitis, the 200 mg daily dose seems to be that sweet spot," Dr. Singh said by email. "No unusual side effects were observed at that dose."

For a maintenance study, researchers then re-randomized participants who achieved clinical remission or a Mayo Clinic Score response with filgotinib at week 10. Participants were re-randomized 2:1 to either continue their induction filgotinib regimen or receive a placebo, while those on placebo over the first 10 weeks continued on placebo.

The maintenance study found that at week 58, a significantly higher proportion of patients on filgotinib 200 mg (37.2%) achieved remission compared with placebo (11.2%). At week 58, filgotinib 100 mg was also significantly more effective than placebo for achieving clinical remission (23.8%).

During the maintenance study, adverse events were similar with filgotinib 200 mg, filgotinib 100 mg, and placebo. While two patients died during this study, the fatalities weren't treatment related.

One limitation of the study is the short duration of assessments, the study team notes in The Lancet. Another is the lack of dose escalation or extended therapy beyond the induction phase of the study for non-responders. Senior author Laurent Peyrin-Biroulet of the University of Lorraine in France, didn't respond to requests for comment.

It's also hard to say without a direct comparison to currently approved therapies for ulcerative colitis how a subsequent approval of filgotinib for ulcerative colitis might influence prescribing decisions or clinical care, said Dr. Arthur Kavanaugh, a professor of medicine at the University of California, San Diego, who wasn't involved in the study.

"Clearly, 200 mg was more effective than placebo, and there was a clear trend towards efficacy with the 100 mg," Dr. Kavanaugh said by email. "But the effect sizes were modest, particularly in the population with the biggest unmet need - those refractory/exposed to biologics."

SOURCE: https://bit.ly/3gwx7sG and https://bit.ly/3xiMHyI The Lancet, online June 3, 2021.

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