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Filgotinib (GLPG0634, GS-6034) is a once-daily, orally administered, Janus kinase 1 (JAK1)-selective inhibitor. The FITZROY study examined the efficacy and safety of filgotinib for the treatment of moderate-to-severe Crohn's disease. We did a randomised, double-blind, placebo-controlled phase 2 study, which recruited patients from 52 centres in nine European countries. We enrolled eligible patients aged 18–75 years with a documented history of ileal, colonic, or ileocolonic Crohn's disease for 3 months or more before screening, as assessed by colonoscopy and supported by histology, and a Crohn's Disease Activity Index (CDAI) score during screening between 220 and 450 inclusive. Patients were randomly assigned (3:1) to receive filgotinib 200 mg once a day or placebo for 10 weeks. Patients were stratified according to previous anti-tumour necrosis factor alpha exposure, C-reactive protein concentration at screening (≤10 mg/L or >10 mg/L), and oral corticosteroid use at baseline, using an interactive web-based response system. The primary endpoint was clinical remission, defined as CDAI less than 150 at week 10. After week 10, patients were assigned based on responder status to filgotinib 100 mg once a day, filgotinib 200 mg once a day, or placebo for an observational period lasting a further 10 weeks. The filgotinib and placebo treatment groups were compared using ANCOVA models and logistic regression models containing baseline values and randomisation stratification factors as fixed effects. Analyses were done on the intention-to-treat non-responder imputation set. The trial was registered at ClinicalTrials.gov, number NCT02048618. Between Feb 3, 2014, and July 10, 2015, we enrolled 174 patients with active Crohn's disease confirmed by centrally read endoscopy (130 in the filgotinib 200 mg group and 44 in the placebo group). In the intention-to-treat population, 60 (47%) of 128 patients treated with filgotinib 200 mg achieved clinical remission at week 10 versus ten (23%) of 44 patients treated with placebo (difference 24 percentage points [95% CI 9–39], p=0·0077). In a pooled analysis of all periods of filgotinib and placebo exposure over 20 weeks, serious treatment-emergent adverse effects were reported in 14 (9%) of 152 patients treated with filgotinib and three (4%) of 67 patients treated with placebo. Filgotinib induced clinical remission in significantly more patients with active Crohn's disease compared with placebo, and had an acceptable safety profile. Galapagos.

Filgotinib is a once daily, oral, selective Janus kinase 1 (JAK1) inhibitor, which has demonstrated efficacy in patients with rheumatoid arthritis. Here we analyse patient reported outcomes in patients with moderate-to-severely active Crohn's disease (CD) from the Fitzroy Ph2 study.MethodsOne hundred seventy-four patients with moderate-to-severely active CD (CDAI: 220–450, evidence of active disease by centrally-read endoscopy) were randomized (3:1 ratio) to receive 200 mg filgotinib (FIL) or placebo (PBO) QD for 10 weeks. Immunosuppressants were discontinued prior to treatment initiation. Based on clinical response at Week 10, patients continued to receive filgotinib (200 or 100 mg QD) or placebo for an additional 10 weeks. Both TNF-antagonist naïves and non-responders were included. Clinical efficacy, safety, and patient reported outcomes (IBDQ and PRO2) data from the first 10-week part are presented.ResultsBaseline characteristics were similar in both groups, including mean disease duration (8.3 yr), mean CDAI score (293), mean SES-CD (14.6), oral corticosteroids (51%, mean daily dose 20.8 mg/d). The primary endpoint of the study was met: FIL induced clinical remission (CDAI < 150) in 47% of the patients, compared to 23% of those assigned to PBO (P = 0.0077). At week 10, quality of life, assessed by patient reported outcome PRO2 (PRO2: 7 × [mean daily number of liquid or very soft stools] + 7 × [mean daily abdominal pain score] [mean change from baseline FIL: −21.9; PBO: −15.6; P = 0.0321]) as well as IBDQ score (mean change from baseline FIL: 33.8; PBO: 17.6; P = 0.0046) improved significantly more in FIL compared to PBO. Effect of FIL on IBDQ was evident in all IBDQ subcomponents (mean change from baseline): bowel symptoms (FIL: 10.0; PBO: 5.6; P = 0.0040), systemic symptoms (FIL: 5.7; PBO: 2.9; P = 0.0044), emotional status (FIL: 12.1; PBO: 6.1; P = 0.0094), and social functioning (FIL: 6.2; PBO: 2.9; P = 0.0202). The IBDQ remission (IBDQ score ≥ 170) (FIL: 45%; PBO: 27%; P = 0.0505) and IBDQ response (change in IBDQ score ≥16) (FIL: 64%; PBO: 41%; P = 0.0137) were higher with FIL compared to PBO. The patient's general well-being (CDAI component, mean change from baseline FIL: −0.98; PBO: −0.65; P = 0.1024) improved more with FIL compared to PBO at week 10, but statistical significance was not reached. Improvements in clinical CDAI responses correlated with improvements in patient reported outcomes. Overall, filgotinib was safe and well tolerated. The rates of early discontinuation, SAEs and TEAEs including infections were similar in the FIL and PBO groups; the majority of the SAEs was related to worsening of CD.ConclusionsFilgotinib is the first JAK inhibitor to show efficacy in moderate-to-severely active CD. JAK1 inhibition with filgotinib induces clinical remission, associated with improved quality of life as demonstrated by patient-reported outcome measures. The efficacy and safety profile of filgotinib demonstrates its potential as an oral treatment with a novel mechanism of action for the treatment of CD.