Insights on Filgotinib in Crohn’s Disease From the DIVERSITY1 and SELECTION Studies

Filgotinib is a JAK inhibitor approved by the European Medicines Agency for the treatment of patients with moderately to severely active UC.¹ The double-blind, phase 3 DIVERSITY1 study investigated filgotinib vs placebo as induction and maintenance therapy in patients with moderately to severely active CD.² Patients were evenly randomized to receive 100 or 200 mg of filgotinib daily or placebo for 10 weeks during induction or through week 58 for maintenance therapy. Induction study A included patients with or without prior biologic exposure, and study B included only patients who were biologic-experienced. After the induction period, patients with a response to filgotinib were randomized in a 2:1 ratio to continue with filgotinib at the induction dose or to receive placebo. The study had 2 primary endpoints: clinical remission, defined as a CDAI of less than 150, and endoscopic response, defined as a reduction of at least 50% in the Simple Endoscopic Score for Crohn’s Disease (SES-CD) from baseline or clinical remission on the basis of a 2-item PRO.

The DIVERSITY1 study enrolled 1363 patients into 6 arms. After 10 weeks of induction therapy, the rate of clinical remission was significantly higher among the patients treated with 200 mg of filgotinib than among those treated with placebo in study A (32.9% vs 19.8%; P=.017) and in study B (26.7% vs 14.8%; P=.0023) (Figure 7). However, the rates of endoscopic response were not significantly different for filgotinib vs placebo in either study A or study B (P>.05). In the maintenance portion of the study, the only comparison that was significant was the rate of endoscopic response in patients who received 200 mg of filgotinib for both induction and maintenance vs the rate in patients who initially received the higher dose of filgotinib and were then randomized to placebo for maintenance (30.4% vs 9.4%; P=.0038).

Figure 7.

Coprimary endpoints at week 10 of IND study A and IND study B and at week 58 of the MNT study of filgotinib in

Crohn’s disease from the phase 3 DIVERSITY1 trial.

^aThe FAS for the IND studies included all randomized patients who received ≥1 dose of filgotinib or placebo.

^bThe FAS for the MNT study included all rerandomized responders (endoscopic response or PRO2 clinical remission at week 10) who received ≥1 dose of filgotinib or placebo during the MNT study.

Δ, difference; CDAI, Crohn’s Disease Activity Index; FAS, full analysis set; FIL, filgotinib; FIL100, filgotinib 100 mg; FIL200, filgotinib 200 mg; IND, induction; MNT, maintenance; PBO, placebo; PRO2, 2-item patient-reported outcome.

Adapted from Vermeire et al. Abstract P0727. Presented at: ACG 2023; October 20-25, 2023; Vancouver, British Columbia, Canada.⁴

The international phase 2b/3 SELECTION study compared filgotinib at 100 or 200 mg daily vs placebo in 1348 patients with moderately to severely active UC.³ In a safety analysis, patient data from the 2 studies were used to compare filgotinib toxicity in patients with UC vs toxicity in patients with CD.⁴ Filgotinib was generally well tolerated, with no new safety signals arising. Rates of specific AEs, such as serious infections, malignancies excluding nonmelanoma skin cancer, venous thromboembolism, and major adverse cardiovascular events, were similar among patients with CD and those with UC. A gastrointestinal perforation developed in 11 of the patients with CD, but none was considered related to filgotinib therapy. No deaths occurred that were considered related to study treatment.