• Julián Panés, Geert R D'Haens, Higgins Peter D R PDR Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan., Linda Mele, Michele Moscariello, Gary Chan, Wenjin Wang, Wojciech Niezychowski, Chinyu Su, and Eric Maller.
• Inflammatory Bowel Diseases Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
• Aliment. Pharmacol. Ther. 2019 Feb 1; 49 (3): 265-276.

BackgroundTofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease.AimsThis 48-week open-label extension study primarily investigated long-term safety of tofacitinib 5 and 10 mg b.d. and secondarily investigated efficacy as maintenance therapy in patients with Crohn's disease.MethodsPatients who had completed the phase 2b maintenance study, or withdrawn due to treatment failure, were enrolled. Patients in remission (Crohn's disease activity index <150) at baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. A single dose adjustment was allowed after 8 weeks' fixed, open-label treatment.ResultsSixty-two patients received tofacitinib 5 mg b.d.; 88 received 10 mg b.d. Both groups had similar rates of adverse events and serious infections. Crohn's disease worsening was the most frequent adverse event for tofacitinib 5 (33.9%) and 10 mg b.d. (19.3%). Patients not in remission at baseline, receiving 10 mg b.d., had higher rates of serious adverse events (19.3%) and discontinuation attributed to insufficient clinical response (30.7%) vs 5 mg b.d. (8.1% and 9.7%, respectively). At week 48, of patients with baseline remission receiving 5 mg b.d., 87.9% maintained remission and 75.0% sustained remission as observed (46.8% and 38.7%, respectively, by non-responder imputation). Study design prevented between-dose efficacy comparisons.ConclusionsNo new safety signals emerged. Although both doses showed generally similar safety outcomes for overall adverse events, serious adverse events were more frequent for tofacitinib 10 than 5 mg b.d. Discontinuation due to insufficient clinical response was lower among patients in remission at baseline. ClinicalTrials.gov: NCT01470599.© 2019 John Wiley & Sons Ltd.

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