Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: Filgotinib induced clinical remission in significantly more patients with active Crohn's disease compared with placebo, and had an acceptable safety profile. FUNDING: Galapagos.

Severity of gastroesophageal reflux disease influences daytime somnolence: a clinical study of 134 patients underwent upper panendoscopy.

AIM: To asses the relationship between severity of gastroesophageal refluxe disease and Epworth sleepiness scale as an indicator of daytime somnolence. METHODS: One hundred and thirty-four patients underwent an upper panendoscopy as indicated by the typical reflux symptoms and were also investigated with regard to somnolence. Sleepiness was evaluated by Epworth Sleepiness Scale, which was compared to the severity of endoscopic findings (Savary-Miller/modified by Siewert). Patients with psychiatric disorders or being on sedato-hypnotics as well as shift workers were excluded from the study. The relationship between the severity of the reflux disease and daytime somnolence was analyzed with the help of multivariate regression analysis. RESULTS: A positive tendency was found between the severity of the reflux disease and the corresponding Epworth Sleepiness Scale. In the case of the more severe type - Savary-Miller III - at least a mild hypersomnia was found. For this group daytime somnolence was significantly higher than in the case of the non-erosive type of Gastroesophageal Reflux Disease representing the mildest stage of reflux disease. CONCLUSION: The severity of Gastroesophageal Reflux Disease influences daytime somnolence.

[Comparison of the effectiveness and tolerability of the saccharosum-sennosid-B solution and sodium-picosulfate in preparation for colonoscopy. Prospective, multicenter, randomized study]. / A saccharosum + sennosid-B oldat és a Na-pikoszulfát effektivitásának és tolerálhatóságának összehasonlítása kolonoszkópos elókészítés során. Multicentrikus, prospektív, randomizált vizsgálat.

INTRODUCTION: The effectivity, evaluability of the colonoscopic procedure depends greatly on the preparation and the cleanliness of the colon. A large scale of laxatives used for colon preparation are also available in our country (phenolphtalein, Karlsbad-salt, saccharosum + sennosid-B solution, bisacodyl, powder mixtures). AIMS: The authors examined in 5 gastroenterology centres the tolerability and effectivity of two frequently used laxatives--saccharosum + sennosid-B solution and Na-picosulphate--during colonoscopic preparation in 157 patients. METHODS: Exclusion criteria were: severe anemia, renal insufficiency, cardiac failure, active ulcerative colitis and Crohn's disease, possible stenotising colonic process and hypersensibility to one of the compounds. The patients were randomised prospectively. In the case of the saccharosum + sennosid-B solution the colon preparation was performed according to the manufacturers prescriptions, in the case of the Na-pikosulfate the investigator's own procedure was used based on literature data. The tolerability of the preparation was assessed using a questionnaire. The investigators made their statements concerning the cleanliness of the different colon sections based on uniform criteria. RESULTS: Both methods showed good efficacy concerning the cleanliness of the colon. The patients considered the Na-picosulphate better tolerable--based on the questionnaire data. The authors consider the analysis of further laxatives to help improve the work of their fellow endoscopists.