Abstract
Background
Patients with ulcerative colitis (UC) often do not respond to treatment or lose response over time, and thus switch between therapies with various mechanisms of action (MoAs).1 Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor in development as a UC treatment. We assessed the efficacy of FIL in biologic (bio)-naïve and bio-experienced patients with UC, and in bio-experienced patients with failure of 1 or ≥2 biologics or 1 or 2 MoAs.
Methods
SELECTION (NCT02914522) was a phase 2b/3 double-blind, randomised, placebo-controlled trial comprising two induction studies and a maintenance study. Adults (18–75 years) with moderately to severely active UC were randomised 2:2:1 to FIL 200 mg, FIL 100 mg or placebo (PBO) once daily for 11 weeks in Induction Study A (bio-naïve) and B (bio-experienced). Patients in either clinical remission or Mayo Clinic Score (MCS) response at week 10 (responders) could enter the Maintenance Study. Responders who received induction FIL were re-randomised 2:1 to continue their induction regimen or PBO through week 58. Responders who received induction PBO continued PBO. We assessed clinical remission and MCS response at weeks 10 and 58 in bio-naïve patients and bio-experienced patients with failure of 1 or ≥2 biologics and 1 or 2 MoAs (TNF antagonists and vedolizumab). All p values for subgroup analyses are nominal.
Results
At week 10, clinical remission was achieved by a significantly higher proportion of bio-naïve and -experienced patients treated with FIL 200 mg than PBO (Figure 1a). A higher proportion of bio-experienced patients with 1 biologic or MoA failure treated with FIL 200 mg than PBO achieved clinical remission at week 10 (p<0.05); a smaller treatment effect was seen in patients with ≥2 biologic or 2 MoA failures (Figure 1b). None of these comparisons reached p<0.05 for FIL 100 mg. Higher proportions of patients treated with either dose of FIL than PBO achieved MCS response at week 10 in all (sub)groups (Figure 2). At week 58, higher proportions of bio-naïve and -experienced responders, and bio-experienced responders with ≥2 biologic or 2 MoA failures treated with maintenance FIL 200 mg than PBO achieved clinical remission (p<0.05) (Table 1). Higher proportions of responders treated with maintenance FIL 200 mg than PBO achieved MCS response at week 58 in all (sub)groups.
Conclusion
FIL 200 mg was effective in inducing and maintaining clinical remission in bio-naïve and -experienced patients. Induction results suggest FIL 200 mg is most effective in bio-naïve patients, and those who switch after failure of 1 biologic or MoA. Interpretation of week 58 data is limited by low patient numbers.
Reference
P206 - Which patient population profits best from a high dose, once daily treatment with 3.0g mesalazine for maintaining clinical remission in ulcerative colitis? A subgroup analysis of a double-blind, double-dummy, randomised, controlled, dose-ranging study
