Background: Filgotinib is an oral, selective Janus kinase 1 (JAK1) inhibitor, which demonstrated efficacy in patients with rheumatoid arthritis. This 20-week Phase 2 study evaluated the efficacy and safety of filgotinib in patients with moderate-to-severely active Crohn's disease (CD). The primary endpoint (CDAI remission at Week 10) was met with an acceptable safety profile. Here, efficacy data from the exploratory Week 10–20 period as well as overall safety data are presented.
Methods: 174 patients with moderate-to-severely active CD (CDAI: 220 to 450) and ulcerations confirmed by centrally read endoscopy were randomized 3:1 to receive 200mg filgotinib (FIL) or placebo (PBO) QD for 10 weeks. Immunosuppressants were to be discontinued prior to treatment initiation but corticosteroid-treated patients remained on stable doses until Week 10. Based on clinical response at Week 10 (CDAI decrease from baseline ≥100, as calculated by the investigator), patients were assigned to FIL (200mg or 100mg QD) or PBO for an additional 10 weeks. Patients assessed as clinical responders underwent mandatory corticosteroid tapering after Week 10. The second part of the study was exploratory.
Results: Baseline characteristics were similar in both initial treatment groups, including mean disease duration (8.3 y), mean CDAI score (293), mean CRP (15.6 mg/L, 41%>10mg/L), oral corticosteroids (51%, mean daily dose 20.8 mg/day).
At Week 20, 50–71% of initial FIL 200mg responders showed clinical remission and 67–79% showed clinical response, depending on their assignment to FIL 200mg QD, FIL 100mg QD or PBO. The FIL initial responders also maintained their gains in quality of life, as revealed by an IBDQ score at Week 20 that was at least 38.1 points higher than baseline. 59% (13/22) of patients not responding to PBO after 10 weeks showed clinical response at Week 20 upon being switched to FIL 100mg QD, and 32% (7/22) showed clinical remission.
The proportion of patients experiencing at least one TEAE was 75% with FIL (all periods of FIL exposure) and 67% with PBO (all periods of PBO exposure). Serious TEAEs occurred in 9% of FIL patients and 4% of PBO patients. TEAEs leading to discontinuation occurred in 18% for FIL and 9% for PBO. Serious infections were reported in 3% of FIL patients, and none in the PBO group.
Conclusions: Clinical efficacy, induced with filgotinib after 10 weeks of treatment, as well as IBDQ improvements were sustained through Week 20 despite mandatory steroid tapering. 100mg filgotinib also showed efficacy, however this needs to be further evaluated. The efficacy and safety data of filgotinib suggest a favourable risk/benefit profile.