PGI4 A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS TO EVALUATE THE EFFICACY AND SAFETY OF TOFACITINIB IN THE TREATMENT OF MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS

Abstract

To compare the clinical efficacy and safety of tofacitinib, an orally administered small molecule therapy, with approved biologic therapies for the treatment of moderately to severe active ulcerative colitis (UC). A systematic review was conducted to identify randomised controlled trials (RCTs) reporting pre-defined efficacy and safety endpoints for tofacitinib or biological therapies (adalimumab, golimumab, infliximab and vedolizumab). Clinical response and clinical remission after a short-term induction phase (6-10 weeks) and at the end of a longer-term maintenance phase (52-60 weeks) were evaluated using a random effects Bayesian multinomial likelihood model with probit link. Patients with and without prior exposure to TNF inhibitor (TNFi) drugs were considered separately. Sensitivity analyses tested alternatives to the population inclusion criteria (TNFi-failure vs TNFi-exposure) and clinical endpoints (centrally versus locally assessed endoscopic sub-scores). Safety outcomes, including serious infections, were also explored. The network meta-analyses (NMA) adhered to NICE-recommended methods. Searches of Medline, Embase and Cochrane were last performed April 2019. Seventeen RCTs were included in the NMAs. No statistically significant differences between biological therapies and tofacitinib for either TNFi-naïve or TNFi-exposed patients were observed. In TNFi-naïve patients, all therapies were more efficacious than placebo, with infliximab, vedolizumab and tofacitinib ranked best in induction and tofacitinib, vedolizumab and golimumab ranked best in maintenance. In TNFi-exposed patients, only tofacitinib was significantly more efficacious than placebo as induction therapy, and only tofacitinib and vedolizumab were significantly more efficacious as maintenance therapies. Results of the NMA sensitivity analyses were consistent with the base case. There were no significant differences in serious infection rates among therapies. This study provides a contemporary and robust assessment of the relative efficacy and safety of targeted therapies for patients with UC, with specific regard for TNFi-naïve and TNFi-exposed subgroups. These results show that tofacitinib is efficacious in both populations.