The Selection study was a multi-centre, randomized, double-blind, placebo-controlled study comprising two induction trials and a maintenance trial. The Induction Study A enrolled biologic-naïve patients, and the Induction Study B enrolled biologic-experienced patients.
The study was designed to investigate the efficacy and safety of filgotinib versus placebo for the treatment of moderate to severe UC. A key secondary endpoint was 6-month CS-free remission, assessed in the maintenance study using the following outcomes: 1-, 3-, 6- and 8-month rates of CS-free (no systemic or localised CS use indicated for UC, continuously, for the specified time period before Week 58) clinical remission at Week 58, as well as the change in median daily prednisone‑equivalent dose over time.1
Patients in the refractory population had a high inflammatory burden: 27.7 percent of participants had prior use of ≥2 biologic agents; 37.6 percent had prior anti-TNF failure; 19.8 percent had prior vedolizumab failure and 48.5 percent had a history of pancolitis.1
Eligible participants (n=1,351) were randomised 2:2:1 to filgotinib 200 mg once daily (QD), filgotinib 100 mg QD or placebo for 10 weeks. Patients who achieved clinical remission or Mayo Clinic Score response at Week 10 were re‑randomised 2:1 at Week 11.1,2
At maintenance Week 14, participants receiving filgotinib 200 mg QD (n=92) or placebo (n=47) who were on CSs were required to reduce their daily doses, starting at a reduction rate of 2.5 mg every week (QW), up to 5 mg QW (3 mg every 3 weeks for patients receiving budesonide), until they were no longer on CSs. If symptoms returned, the CS dose could be increased or restarted, up to the baseline dose. However, treatment was considered to have failed for patients who received a CS dose higher than their baseline dose (non-responders).1
The results show that at week 58, among patients receiving CSs at maintenance study baseline, 30.4%, 29.3%, 27.2% and 21.7% of patients receiving filgotinib were in CS‑free remission for ≥1, 3, 6 or 8 months, respectively, versus 6.4% of patients receiving placebo (p<0.05).1
During the maintenance study, the median daily prednisone-equivalent dose decreased from 17.5 to 10 mg QD with filgotinib 200 mg QD treatment; this CS-sparing effect was maintained over time.1
Further, the results show that among patients in the full analysis set receiving filgotinib in the maintenance study, a numerically greater proportion of patients who had been CS free for 6 months at Week 58 were also in inflammatory bowel disease questionnaire IBDQ remission at Week 58 compared with patients who had not been CS free for 6 months.1
In the absence of head-to-head trials, a matching-adjusted indirect comparison (MAIC) of maintenance studies (SELECTION, GEMINI 1, VISIBLE 1 and OCTAVE SUSTAIN) was conducted to determine the CS‑free clinical remission with filgotinib 200 mg QD, intravenous (IV) vedolizumab 300 mg every 8 weeks, subcutaneous (SC) vedolizumab 108 mg every 2 weeks and oral tofacitinib 5 mg twice daily.1
Based on the MAIC, filgotinib 200 mg was associated with a greater likelihood of CS-free clinical remission versus IV vedolizumab 300 mg for patients who were biologic naïve (odds ratio [OR] 15.2; 95% confidence interval [CI]=1.6, 139.9; p<0.05). Numerically higher odds were also observed between filgotinib 200 mg and SC vedolizumab 108 mg in patients who were biologic naïve (OR 3.8; 95% CI=0.2, 63.8; p=0.36) and biologic experienced (OR 3.2; 95% CI=0.2, 60.5; p=0.44), and between filgotinib 200 mg and tofacitinib 5 mg for the overall population (OR 2.0; CI=0.4, 9.1; p=0.39).1
Among patients receiving CSs at baseline and filgotinib in the maintenance study, the safety analysis did not show meaningful differences in the proportion of adverse events (AEs) between subgroups of patients who were or were not in 6-month, CS-free remission at Week 58.1
1. Loftus EV, Vermeire S, Feagan BG, et al. Corticosteroid-sparing effects of filgotinib in moderate to severely active ulcerative colitis: data from the phase 2b/3 SELECTION study. J Crohns Colitis 2022; jjac122. 2. ClinicalTrials.gov. Study to evaluate the efficacy and safety of filgotinib in the induction and maintenance of remission in adults with moderately to severely active ulcerative colitis (SELECTION). Available at: https://clinicaltrials.gov/ct2/show/NCT02914522?term=NCT02914522&draw=2&rank=1 (accessed September 2022).