Efficacy of Filgotinib in Patients with Ulcerative Colitis by Line of Therapy in the Phase 2b/3 SELECTION Trial

Abstract

Abstract Background and Aims The efficacy of new therapies for ulcerative colitis [UC] is usually influenced by previous biologic use. These post hoc analyses of SELECTION, a placebo-controlled phase 2b/3 trial in patients with moderately to severely active UC, evaluated the efficacy of filgotinib, an oral Janus 1 kinase preferential inhibitor, with respect to prior biologic failure. Methods The effect of filgotinib 200 mg (FIL200) relative to placebo was compared in biologic-naïve and biologic-failed patient groups, and in further subgroups by number of failed biologics [1 or >1], biologic mechanism of action [MoA] classes [1 or 2] and tumour necrosis factor [TNF] antagonists [1 or >1]. Odds ratios [ORs] for clinical remission at week 10 [induction] and hazard ratios [HRs] for protocol-specific disease worsening [PSDW] from week 11 to week 58 [maintenance] were calculated. Results At week 10, FIL200-treated patients were more likely to achieve clinical remission than placebo-treated patients in the biologic-naïve (OR [95% confidence interval, CI]: 1.98 [1.14–3.44]) and biologic-failed (3.91 [1.33–11.48]) groups. During maintenance, FIL200-treated patients had a reduced risk of PSDW in the biologic-naïve (HR [95% CI]: 0.22 [0.11–0.44]) and biologic-failed (0.22 [0.12–0.40]) groups, and in all biologic-failed subgroups (except >1 TNF antagonist failure). The data suggest that the likelihood of PSDW at week 58 increased with increasing numbers of failed biologics. Conclusions FIL200 induced and maintained benefits relative to placebo regardless of previous biologic use; however, the estimated therapeutic benefit was greatest in biologic-naïve patients and patients previously treated with one biologic or biologic MoA class. [ClinicalTrials.gov: NCT02914522].