Filgotinib Effective as Both First- and Second-Line Treatment in Ulcerative Colitis

A post hoc analysis found that filgotinib has superior outcomes compared with placebo among patients with ulcerative colitis (UC), regardless of prior exposure to biologics. The study findings were published in the Journal of Crohn’s and Colitis.

Efficacy of treatments often depend on prior exposures to biologic therapies in the setting of UC. As such, this post hoc analysis was designed to evaluate the efficacy of filgotinib on the basis of patient treatment history.

Data for this study were sourced from the SELECTION (ClinicalTrials.gov Identifier: NCT02914522) study, which was a double-blind, randomized, placebo-controlled phase 2b/3 trial that enrolled both treatment-naive and -experienced patients with moderate to severe UC. Patients were randomly assigned to receive 100 or 200 mg filgotinib or placebo for 11 weeks. Those who achieved clinical response or remission were rerandomly assigned to continue on filgotinib or switch to placebo for 58 weeks. For this analysis, outcomes were compared between patients who were biologic-naive (n=665) or had biologic failure (n=649) at baseline.

Among the naive and failure groups, 248 and 246 received 200 mg filgotinib; 277 and 271 received 100 mg filgotinib; and 140 and 132 received placebo, respectively. The groups had a mean age of 41.5 to 44.2 years, 33.6% to 49.6% were women, 67.7% to 75.3% were White, mean Mayo Clinic Scores (MCSs) were 8.6 to 9.3 points, and 30.0% to 47.6% had concomitant corticosteroid use.

Compared with placebo, biologic-naive recipients of 200 mg filgotinib were more likely to achieve clinical remission (odds ratio [OR], 1.98) and MCS response (OR, 2.25) at week 10. Similar findings were observed among the biologic failure high-dose filgotinib recipients for achieving clinical remission (OR, 3.91) and MCS response (OR, 6.50) compared with placebo.

Among the biologic failure group, the subset of patients who had 1 prior failure (OR, 9.36) and 1 mechanism of action (MoA) failure (OR, 3.64) was more likely to achieve clinical remission with 200 mg filgotinib at week 10 compared with placebo. For achieving MCS response, 200 mg filgotinib associated with response at 10 weeks compared with placebo among those with 1 prior failure (OR, 6.95), more than 1 prior failure (OR, 6.33), 1 MoA failure (OR, 7.42) 2 MoA failures (OR, 5.76), 1 tumor necrosis factor (TNF) antagonist failure (OR, 11.52), and more than 1 TNF antagonist failure (OR, 9.30).

The subset of patients who continued receiving 200 mg filgotinib during the maintenance phase of the trial had lower risk for protocol-specific disease worsening (PSDW) compared with those who switched to placebo among both the biologic-naive (hazard ratio [HR], 0.22) and -failed (HR, 0.22) cohorts.

Among the biologic failure group, PSDW was less likely among the 200 mg filgotinib group compared with placebo for those with 1 biologic failure (HR, 0.18), more than 1 biologic failure (HR, 0.25), 1 MoA failure (HR, 0.27), 2 MoA failures (HR, 0.17), and 1 TNF antagonist failure (HR, 0.13).

This analysis may be limited, as only responders continued into the maintenance phase of this study.

“[T]hese data support the efficacy of filgotinib 200 mg as induction and maintenance therapy for UC regardless of treatment history, with the greatest sustained benefits observed when filgotinib is used as a first-line therapy before biologics or as a second-line therapy after failure of only 1 biologic or biologic MoA class,” the study authors concluded.

Disclosures: This research was supported by Galapagos NV. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.