Long‐term safety and tolerability of oral tofacitinib in patients with Crohn's disease: results from a phase 2, open‐label, 48‐week extension study. Issue 3 (20th January 2019)

• Record Type: Journal Article
• Authors: Panés, Julián; D'Haens, Geert R.; Higgins, Peter D. R.; Mele, Linda; Moscariello, Michele; Chan, Gary; Wang, Wenjin; Niezychowski, Wojciech; Su, Chinyu; Maller, Eric
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 49:Issue 3(2019)
• Page Start: 265
• Page End: 276
• Publication Date: 2019-01-20
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.15072
• Languages: English
• ISSNs: 0269-2813

Abstract

Summary: Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease. Aims: This 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. Methods: Patients who had completed the phase 2b maintenance study, or withdrawn due to treatment failure, were enrolled.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. Results: Sixty‐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. Conclusions: No 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.