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].