Patients with Crohn's Disease Treated with Filgotinib Experienced Higher Rates of Clinical Remission and Improved Quality of Life Compared to Patients Who Received Placebo

“Filgotinib is the first JAK inhibitor to show efficacy in Crohn’s disease,” said Severine Vermeir, MD, of Leuven University Hospital in Belgium, at a presentation at Digestive Disease Week 2016, a joint meeting of the American Academy for the Study of Liver Diseases (AASLD), American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).

Filgotinib is a novel oral, potent and selective Janus kinase 1 (JAK1) inhibitor that has previously demonstrated high efficacy in patients with rheumatoid arthritis. The FITZROY study is a 20-week phase 2 double-blind, placebo-controlled study designed to evaluate the efficacy and safety of filgotinib, 200 mg/day, in patients with active moderate-to-severe Crohn’s disease (Crohn’s Disease Activity Index [CDAI] score of 220 to 450, Simplified Endoscopy Score for CD ≤7). Patients were required to either be anti-tumor necrosis factor (TNF)-naïve or anti-TNF nonresponders. Immunosuppressants were discontinued prior to study entry.

The results presented here were data from the first part of the study—the 10-week induction phase, which included the primary endpoint of clinical remission (CDAI <150) at Week 10. The average disease duration was 8.3 years, mean CDAI score was 293, mean CRP value was 15.6 mg/L, and 41% of patients had a C-reactive protein (CRP) value over 10 mg/L. Half (49%) of patients used oral corticosteroids, with a mean daily dose of 23.2 mg.

At Week 10, a statistically significant higher CDAI remission rate was observed for patients on filgotinib versus placebo. Significantly more patients on filgotinib demonstrated clinical response (CDAI-100) and improved quality of life, as measured using the Inflammatory Bowel Disease Questionnaire (IBDQ) scale. About twice as many filgotinib-treated patients achieved normalized CRP compared with placebo (30$ vs. 14%).

The safety profile of filgotinib in the induction phase of the FITZROY study was similar to that reported in the previously conducted DARWIN studies conducted in patients with rheumatoid arthritis. The majority of serious adverse events related to worsening of Crohn’s disease. Mean hemoglobin concentrations increased similarly for both treatment groups. No clinically significant changes from baseline in mean neutrophil counts or liver function tests were observed. Filgotinib showed an increase in high-density lipoprotein-cholesterol (HDL-C) and no change in low-density lipoprotein cholesterol (LDL-C), resulting in a favorable lipid profile.

Filgotinib is the first oral, JAK1-selective inhibitor showing efficacy in moderate-to-severe Crohn’s disease patients. Filgotinib induced clinical remission (48% vs. 23%, p=0.0067) and clinical response (60% vs. 41%, p=0.0386) and significantly improved quality of life (33.82 vs. 17.56, p=0.0045). During 10 weeks of treatment, filgotinib was well tolerated, with no unexpected safety findings.

“These data are robust and important because, collectively, they show that patients who received filgotinib had higher rates of clinical remission and their quality of life improved considerably. This was further accompanied by a significant proportion of patents normalizing their CRP, an objective biomarker of inflammation. It is also important to note that, during the first 10 weeks of dosing, no unexpected safety findings emerged,” she concluded.