Filgotinib offers new promise for managing Crohn’s disease

Trial reveals filgotinib’s potential to redefine Crohn’s disease treatment by delivering sustained remission and improved safety outcomes for patients worldwide.

Study: Efficacy and safety of filgotinib as induction and maintenance therapy for Crohn’s disease (DIVERSITY): a phase 3, double-blind, randomised, placebo-controlled trial. Image Credit: Lightspring / Shutterstock.com

In a recent study published in The Lancet Gastroenterology & Hepatology, researchers assess the efficacy and safety of filgotinib, a Janus kinase (JAK) 1 preferential inhibitor, as induction and maintenance therapy in patients with moderately to severely active Crohn’s disease.

Current treatments for Crohn’s disease

Crohn’s disease is characterized by transmural inflammation that significantly affects the physical, psychological, and social well-being of affected individuals. Current treatments aim to induce and maintain clinical and endoscopic remission, improve health-related quality of life, and reduce disability rates.

Common drug classes used to treat Crohn’s disease include corticosteroids, immunomodulators, and biologic therapies targeting tumor necrosis factor (TNF), interleukin (IL) subunits, or integrins. Although biologics have improved patient outcomes, they are associated with numerous challenges, including primary non-response, secondary loss of efficacy, and safety concerns.

Thus, there remains an urgent need to develop alternative therapies with novel mechanisms of action to manage this debilitating disease. JAK inhibitors, including upadacitinib, show promise; however, further research is essential to develop effective, durable, and well-tolerated treatment options.

About the study

The current study discusses the findings of a phase three clinical trial conducted across 371 centers in 39 countries. The clinical trial adhered to Good Clinical Practice guidelines and the Declaration of Helsinki, with ethical approvals and informed consent obtained. 

Study participants between 18 and 75 years of age with a Crohn’s Disease Activity Index (CDAI) score between 220 and 450, active disease confirmed by the Simple Endoscopic Score for Crohn’s Disease (SES-CD), and specific abdominal pain and stool frequency criteria were eligible. Laboratory tests evaluated hepatic, renal, and hematologic parameters.

Patients were stratified based on prior biologic therapy exposure. Biologic-naive patients were enrolled in induction study A, and biologic-experienced patients were enrolled in study B.

Patients were randomized to receive 200 mg or 100 mg filgotinib or placebo for 11 weeks. Responders achieving clinical or endoscopic remission were re-randomized to continue their filgotinib dose or placebo in a 58-week maintenance study.

Blinding was maintained throughout the study period. Filgotinib efficacy was measured by clinical remission and endoscopic response rates.

Treatment safety was monitored through adverse events and pharmacokinetic assessments. Statistical analyses ensured accurate evaluation by providing a comprehensive assessment of the therapeutic potential of filgotinib in managing Crohn’s disease.

Study findings

Between October 31, 2016, and November 11, 2022, 2,634 patients were screened for eligibility for the induction studies, 707 and 665 of whom were enrolled in induction studies A and B, respectively. Study participants were randomized to receive filgotinib 200 mg of filgotinib, 100 mg, or placebo for 11 weeks.

Completion rates were 89% in study A and 84% in study B. At week 11, 335 filgotinib-treated patients were re-randomized for the maintenance study alongside 146 placebo-treated patients, 48% of whom completed the 58-week maintenance phase.

Baseline demographics and clinical characteristics were generally balanced across treatment groups in all studies. Induction study A comprised 75% White, 20% Asian, and 2% Black or African American participants, whereas study B comprised 78% White, 12% Asian, and 3% Black or African American participants. The proportion of biologic-experienced patients was higher in Study B compared to Study A at 99% and 46%, respectively.

In induction study A, 200 mg filgotinib resulted in a higher but not statistically significant rate of patient-reported outcome (PRO2) clinical remission and endoscopic response compared to placebo. In study B, 200 mg filgotinib achieved statistically significant improvements in PRO2 clinical remission at 11.9% but not in endoscopic response.

Secondary endpoints, including CDAI clinical remission, showed nominal significance in both studies for 200 mg filgotinib. In the maintenance study, 200 mg filgotinib consistently outperformed placebo in PRO2 clinical remission, endoscopic response, and sustained PRO2 clinical remission.

Safety profiles were comparable across groups, with most treatment-emergent adverse events (TEAEs) mild or moderate. Common TEAEs included abdominal pain, headache, and nausea.

Serious TEAEs were reported at similar rates across treatment groups in study A but were higher for 100 mg filgotinib in study B. Gastrointestinal perforations reported in both induction studies were adjudicated as unrelated to treatment.

In the maintenance study, serious TEAEs were more frequently reported with 200 mg filgotinib and included Crohn’s disease exacerbations. No deaths occurred in the induction or maintenance studies. Laboratory abnormalities, infections, and pharmacokinetic data supported the safety profile.

Conclusions

The current clinical trial demonstrated that 200 mg filgotinib is an effective treatment for Crohn’s disease. It met co-primary maintenance endpoints of PRO2 clinical remission and endoscopic response despite failing to meet induction endpoints. High placebo response rates, which could be attributed to corticosteroid use, and the inclusion of difficult-to-treat patients may have influenced outcomes. Taken together, 200 mg filgotinib was well tolerated, with no new safety concerns, thereby aligning with its established safety profile.