Tofacitinib for induction of remission in ulcerative colitis: systematic review and meta-analysis

Abstract

Background: The aim of the study was to assess the efficacy and safety of tofacitinib and its impact on quality of life in patients with moderate-to-severe ulcerative colitis.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials comparing tofacitinib with placebo or any active comparator. We searched Medline, Embase, the Cochrane Library and gray literature for articles published up to May 2017. We synthesized data using a fixed-effect model. We conducted subgroup analysis based on prior exposure to anti-tumor necrosis factor (TNF). We summarized the strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results: We included three trials with 1220 participants. Compared with placebo, tofacitinib was effective in inducing clinical remission (odds ratio [OR] 3.84, 95% confidence interval [CI] 2.29-6.44, I^2: 41%, GRADE: moderate), clinical response (OR 2.95, 95%CI 2.21-3.95, I^2: 0%, GRADE: high), mucosal healing (OR 2.70, 95%CI 1.81-4.03, I^2: 0%, GRADE: high). Tofacitinib was effective in both anti-TNF-naïve and -experienced patients. Tofacitinib had a favorable effect on quality of life. There were no significant differences in the safety profile in terms of the incidence of any or serious adverse events compared to placebo. The risk for infections was increased (OR 1.51, 95%CI 1.05-2.19, I^2: 0%, GRADE: moderate), but the incidence of serious infections did not differ between tofacitinib and placebo.

Conclusion: In patients with moderate-to-severe ulcerative colitis, short-term treatment with tofacitinib is effective for induction of remission and improvement of quality of life.

Keywords: Tofacitinib; meta-analysis; ulcerative colitis.

Figure 1

Flow diagram

Figure 2

Meta-analytic findings for efficacy outcomes *Clinical Remission: Total Mayo score ≤2, with individual subscores ≤1 point, †Remission: Total Mayo score ≤2 points, with individual subscores ≤1 point and a rectal bleeding subscore of 0, ‡Clinical Response: Decrease from induction study baseline in Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or absolute rectal bleeding subscore of 0 or 1, ¦Mucosal healing: Endoscopic subscore ≤1, ¶Endoscopic remission: Endoscopic subscore of 0, **Symptomatic remission: Total Mayo score ≤2 points, with individual subscore ≤1 point, and both rectal bleeding and stool frequency subscore of 0 M-H, Mantel-Haenszel; CI, confidence interval.

Figure 3

Meta-analytic findings for health-related quality of life outcomes IBDQ, Inflammatory Bowel Disease Questionnaire; SD, standard deviation; IV, inverse variance; CI, confidence interval; M-H, Mantel–Haenszel; SF-36 PCS, Short Form-36 Physical Component Summary; SF-36 MCS, Short Form-36 Mental Component Summary.