827 Efficacy and Safety of Tofacitinib in Moderate-Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis

Abstract

INTRODUCTION: Tofacitinib was FDA approved in 2018 for use in patients with moderate to severe ulcerative colitis (UC). It is an oral inhibitor of Janus-kinase 1-3 and can be used in patients who are naïve or have failed other biological therapies. We conducted a systematic review and meta-analysis to assess the overall clinical response and remission of Tofacitinib in patients with moderate-severe UC. METHODS: We conducted a comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, Web of Science databases, Google Scholar and manual search of references (from inception through October 2018) to identify studies that reported use of Tofacitinib in moderate-severe UC patients. The primary outcome was to look at the clinical response and remission and secondary outcome was to look for adverse events. Clinical response was defined as an absolute decrease of Mayo-score by at least 3 points and a relative decrease by at least 30%-with an accompanying decrease in rectal bleeding sub score of at least 1 point or an absolute rectal bleeding sub score of 0 to 1. Clinical remission was defined as total Mayo score of 0 to 2, with no individual sub score exceeding 1. The meta-analysis was performed using Der Simonian and Laird random effect model. RESULTS: A total of 6 studies reporting on 1207 patients receiving 10 mg of Tofacitinib were included in our final meta- analysis. The mean age and follow up were 41.5 years and 15.4 months respectively. 497 patients and 627 patients (using 5/6 studies) were TNF inhibitors naïve and experienced respectively. The overall pooled clinical response and clinical remission of Tofacitinib in moderate-severe UC was 59.68% (95% CI = 55.3- 63.57, I2 = 31.92%) and 31.61% (95% CI = 20.78-43.52, I2 = 92.77%) respectively (Tables 1 and 2). The overall adverse events were 706, which mainly included infections with 22.73% [95% CI = 15.51- 30.83, I2 = 86.13%). The cumulative incidence of Herpes zoster was 0.6% (95% CI = 0.0-2.24, I2 = 67.21%). Significant heterogeneity was noted in the studies included in our meta-analysis. CONCLUSION: Based on the limited data included in our meta-analysis, Tofacitinib (10 mg) seems to have good overall clinical response rate of 59.68%. There was higher rate of infections noted in our meta-analysis. Overall low incidence of Herpes zoster could be due to short follow up (4/6 studies). Further multi-center studies are needed to assess long-term efficacy and safety of Tofacitinib in moderate-severe ulcerative colitis patients.