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.

Ulcerative colitis (UC) is a chronic inflammatory condition of the colon which has a major impact on patients' health related quality of life and a substantial burden on health care budgets. The objective of this analysis was to evaluate the cost-effectiveness of tofacitinib and other approved biologic therapies for the treatment of moderately to severe active UC in the United Kingdom. A Markov model compared the lifetime costs and consequences of treatment with tofacitinib, adalimumab, golimumab, infliximab, vedolizumab and conventional therapy. The analysis took a National Health Service (NHS) perspective and measured benefits in quality-adjusted life years (QALYs). Patients transitioned between health states (defined by treatment and level of disease control) based on results of a network meta-analysis of clinical response and clinical remission. Utility values and estimates of resource use were sourced from systematic reviews of the published literature. Drug, disease monitoring, adverse event and colectomy costs were obtained from UK sources. Analyses were conducted separately for patients with and without prior TNF inhibitor (TNFi) exposure. Deterministic and probabilistic sensitivity analysis were undertaken. The incremental cost-effectiveness ratios for tofacitinib versus conventional therapy were £21,338 and £22,816 per QALY in the TNFi-naïve and TNFi-exposed populations, respectively. TNFi therapies were dominated or extendedly dominated in both populations. Compared with vedolizumab, tofacitinib generated a similar number of QALYs at a lower cost. Results were most sensitive to variation in response and remission rates and to costs of conventional therapy and serious infections. Probabilistic sensitivity analysis showed that tofacitinib had the highest likelihood of being cost effective at a threshold of £30,000 per QALY: 54% and 46% in in TNFi-naïve and TNFi-exposed patients, respectively. Tofacitinib is an efficacious treatment for moderately to severely active UC and is likely to be a cost-effective use of NHS resources.

To compare the clinical efficacy of brodalumab, an anti-IL 17RA human monoclonal antibody, with approved biologic therapies and apremilast for the treatment of moderate-to-severe psoriasis. A PRISMA-compliant systematic literature review identified RCTs reporting induction phase Psoriasis Area Severity Index (PASI) responses for therapies at European Medicines Agency approved doses. The primary analysis examined the proportion of patients achieving PASI 50, 75, 90 or 100 responses using a random effects Bayesian multinomial likelihood model with probit link, without and with an adjustment for study-level placebo responses. A second analysis assessed the number of patients with Physician Global Assessment (PGA) scores of 0 or 1. Effects of alternative inclusion criteria, such as including unlicensed therapies and introducing restrictions based on disease severity, were explored in a series of sensitivity analyses. The NMA adhered to NICE Decision Support Unit recommended methods. A total of 41 studies reporting PASI outcomes were included in the base case NMA. All active therapies were found to be significantly more efficacious than placebo at achieving all levels of PASI response. Based on PASI 100 response (complete clearance), the most efficacious therapies in the network were brodalumab and ixekizumab, followed by infliximab and secukinumab. Brodalumab was significantly more efficacious than adalimumab, apremilast, etanercept and ustekinumab. This ranking was consistent for PASI 50, 75 and 90 outcomes, as well as the PGA response analysis and all sensitivity analyses. Results of the NMA reflect the results from recent pivotal trials which found that high levels of complete clearance can be achieved with brodalumab. Based on currently available evidence, the induction-phase efficacy of brodalumab is similar to ixekizumab, secukinumab and infliximab and superior to other approved therapies, including adalimumab, apremilast, etanercept, and ustekinumab. Analysis of longer-term data is needed to understand the comparative efficacy biological therapies beyond induction.