• Julian Panés, William J Sandborn, Stefan Schreiber, Bruce E Sands, Séverine Vermeire, Geert D'Haens, Remo Panaccione, Higgins Peter D R PDR Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Jean-Frederic Colombel, Brian G Feagan, Gary Chan, Michele Moscariello, Wenjin Wang, Wojciech Niezychowski, Amy Marren, Paul Healey, and Eric Maller.
• Hospital Clinic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
• Gut. 2017 Jun 1; 66 (6): 1049-1059.

ObjectiveTofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD).DesignWe conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study.Results180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p<0.0001) with 10 mg twice daily after both induction and maintenance treatments.ConclusionsPrimary efficacy endpoints were not significantly different from placebo, although there was evidence of a minor treatment effect. No new safety signals were observed for tofacitinib.Trial Registration NumbersNCT01393626 and NCT01393899.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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