Treatment with filgotinib is effective at inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis, according to the results of a study published in The Lancet.
Researchers conducted a study to evaluate the efficacy and safety of filgotinib for the treatment of ulcerative colitis (ClincalTrials.gov identifier: NCT02914522). This phase 2b/3, double-blind, randomized, placebo-controlled trial consisted of 2 induction studies and 1 maintenance study that spanned across 341 study centers in 40 countries.
Eligible patients were between 18 and 75 years of age at screening. They had moderately to severely active ulcerative colitis for at least 6 months before enrollment. Based on their experience with tumor necrosis factor (TNF) antagonists or vedolizumab, patients were enrolled into 1 of 2 induction studies (A and B).
Study participants who had inadequate clinical response, loss of response or intolerance to corticosteroids or immunosuppressants, and were naïve to TNF antagonists and vedolizumab (biologic-naïve) were enrolled in induction study A. Study participants who had an inadequate clinical response, loss of response or intolerance to any TNF antagonists or vedolizumab, and had not used TNF antagonists or vedolizumab within 8 weeks before screening (biologic-experienced) were enrolled in induction study B.
Patients in induction studies A and B were randomly assigned 2:2:1 to receive oral filgotinib 200 mg, filgotinib100 mg, or placebo once per day for 11 weeks. Patients who had either clinical remission or a Mayo Clinic Score response at week 10 entered the maintenance study. Patients in the maintenance study were randomly reassigned (2:1) at week 11 to continue their induction filgotinib regimen or to receive placebo until week 58.
The primary outcome was clinical remission at weeks 10 and 58. The investigators assessed safety in all patients who received at least 1 dose of the study drug or placebo within each study.
Between November 14, 2016, and March 31, 2020, 2040 patients were screened for eligibility. In induction study A, 659 patients were enrolled and were randomly assigned to receive filgotinib 100 mg (n=277), filgotinib 200 mg (n=245), or placebo (n=137). In induction study B, 689 patients were enrolled and were randomly assigned to receive filgotinib 100 mg (n=285), filgotinib 200 mg (n=262), or placebo (n=142).
After efficacy assessment at week 10, 664 patients entered the maintenance study (391 from induction study A and 273 from induction study B). In total, 93 patients continued to receive placebo and 270 patients who had received filgotinib 100 mg in the induction study were randomly assigned to receive filgotinib 100 mg (n=179) or placebo (n=91). In total, 301 patients who had received filgotinib 200 mg in the induction study were randomly assigned to receive filgotinib 200 mg (n=202) or placebo (n=99).
At week 10, a greater proportion of patients given filgotinib 200 mg achieved clinical remission compared with the placebo group (induction study A: 26.1% vs 15.3%; difference, 10.8%; 95% CI, 2.1–19.5; P =.0157; induction study B: 11.5% vs 4.2%; difference, 7.2%; 95% CI, 1.6–12.8; P =.0103). At week 58, 37.2% of patients given filgotinib 200 mg had achieved clinical remission compared with 11.2% in the placebo group (difference, 26.0%; 95% CI, 16.0–35.9; P <.0001).
At week 10, clinical remission was not significantly different between filgotinib 100 mg and placebo, but reached significance by week 58 (23.8% vs 13.5%; difference, 10.4%; 95% CI, 0.0–20.7; P =.0420).
Between treated groups, the incidence of serious adverse events and adverse events of interest were similar. During induction studies A and B, no deaths were reported. During the maintenance study, 2 patients died, but neither death was related to treatment.
This study had several limitations. The assessment had a short duration, which is inherent to randomized controlled trials. Further studies are needed to ascertain the effectiveness and safety of filgotinib in real-world clinical practice.
These data indicated that filgotinib was well tolerated at both 100 mg and 200 mg. Filgotinib was also efficacious in both biologic-naïve and biologic-experienced patients with moderately to severely active ulcerative colitis.
Disclosure: Some study authors declared affiliations with the industry. Please see the original reference for a full list of authors’ disclosures.
Disclosure: This research was supported by Gilead Sciences. Please see the original reference for a full list of disclosures.
Feagan BG, Danese S, Loftus Jr EV, et al. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial. Lancet. Published online June 3, 2021. doi: 10.1016/S0140-6736(21)00666-8