Efficacy and safety of biologic agents and tofacitinib in moderate-to-severe ulcerative colitis: A systematic overview of meta-analyses.

Ulcerative colitis (UC) is an inflammatory disease of the colon and rectum. Treatment options include biologics and tofacitinib. We aim to summarize the evidence on efficacy and safety of biologics and tofacitinib in moderate-to-severe UC. PubMed, Embase, Scopus, and the Cochrane Library were systematically searched to identify meta-analyses of randomized controlled trials assessing adalimumab, golimumab, infliximab, vedolizumab, and tofacitinib in UC. Efficacy outcomes included induction and maintenance of clinical response, clinical remission and mucosal healing. Safety outcomes included adverse events and serious adverse events. The overview involved 31 meta-analyses. All four biologics and tofacitinib were superior to placebo regarding efficacy. Indirect comparisons suggested that infliximab may be better than adalimumab and golimumab to induce clinical response and mucosal healing. Safety analyses indicated no increased rates of adverse events, except for infliximab. Biologics and tofacitinib are efficacious and safe for treating UC. These findings can support clinical decision-making.

Pantavou K ，Yiallourou AI ，Piovani D ，Evripidou D ，Danese S ，Peyrin-Biroulet L ，Bonovas S ，Nikolopoulos GK ... -  《-》

Systematic review with network meta-analysis: comparative assessment of tofacitinib and biological therapies for moderate-to-severe ulcerative colitis.

Biological therapies have improved the care of patients with ulcerative colitis (UC). Tofacitinib, an oral small-molecule Janus kinase inhibitor, is potentially a new treatment option. To comparatively assess efficacy and harm of tofacitinib and biologics (infliximab, adalimumab, golimumab and vedolizumab) in adult patients not previously exposed to TNF antagonists. We performed a comprehensive search of PubMed, Embase, Scopus, clinical trial registries, regulatory authorities' websites and major conference proceedings, through August 2017, to identify randomised, placebo-controlled or head-to-head trials assessing tofacitinib or biologics as induction and/or maintenance therapy in moderate-to-severe UC. Two reviewers independently extracted study data and outcomes, and investigated each trial's risk-of-bias. We used conventional meta-analysis to synthesise direct evidence, and network meta-analysis for adjusted indirect treatment comparisons. Fifteen randomised, double-blind, placebo-controlled trials (n = 3130) contributed data for induction: All treatments are superior to placebo. Indirect treatment comparisons showed that infliximab is better than adalimumab (OR: 2.01, 95% CI: 1.36-2.98) and golimumab (1.67, 1.08-2.59) in clinical response, better than adalimumab (2.10, 1.21-3.64) in clinical remission, and better than adalimumab (1.87, 1.26-2.79) and golimumab (1.75, 1.13-2.73) in mucosal healing. No indirect comparisons between tofacitinib and biologics reached statistical significance. Nine studies (n = 1776) contributed maintenance data showing that all treatments have higher clinical efficacy than placebo. Safety analyses indicated no increased rates of adverse events for the treatments under evaluation (except for infliximab), while vedolizumab may have an advantage regarding the occurrence of serious adverse events. Tofacitinib and biologics are efficacious and safe for UC. Further high-quality research is warranted to establish the best therapeutic option.

Bonovas S ，Lytras T ，Nikolopoulos G ，Peyrin-Biroulet L ，Danese S ... -  《-》

Comparative of the Effectiveness and Safety of Biological Agents, Tofacitinib, and Fecal Microbiota Transplantation in Ulcerative Colitis: Systematic Review and Network Meta-Analysis.

Zhou HY ，Guo B ，Lufumpa E ，Li XM ，Chen LH ，Meng X ，Li BZ ... -  《-》

Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis.

Singh JA ，Hossain A ，Tanjong Ghogomu E ，Mudano AS ，Maxwell LJ ，Buchbinder R ，Lopez-Olivo MA ，Suarez-Almazor ME ，Tugwell P ，Wells GA ... -  《Cochrane Database of Systematic Reviews》

Systematic review with network meta-analysis: first- and second-line pharmacotherapy for moderate-severe ulcerative colitis.

There are limited data to inform positioning of agents for treating moderate-severe ulcerative colitis (UC). To assess comparative efficacy and safety of different therapies as first-line (biologic-naïve) and second-line (prior exposure to anti-tumour necrosis factor(TNF)-α) agents for moderate-severe UC, through a systematic review and network meta-analysis, and appraise quality of evidence (QoE) using grading of recommendations, assessment, development and evaluation (GRADE) approach. We identified randomised controlled trials (RCTs) in adults with moderate-severe UC treated with anti-TNF agents, anti-integrin agents and janus kinase (JAK) inhibitors, as first-line or second-line agents, and compared with placebo or another active agent. Efficacy outcomes were induction/maintenance of remission and mucosal healing; and safety outcomes were serious adverse events and infections. Network meta-analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities. In biologic-naïve patients (12 trials, no head-to-head comparisons), infliximab and vedolizumab were ranked highest for induction of clinical remission (infliximab: odds ratio [OR], 4.10 [95% confidence intervals [CI], 2.58-6.52]; SUCRA,0.85; vedolizumab:SUCRA,0.82) and mucosal healing (infliximab:SUCRA,0.91; vedolizumab:SUCRA,0.81) (moderate QoE). In patients with prior anti-TNF exposure (4 trials, no head-to-head comparisons), tofacitinib was ranked highest for induction of clinical remission (OR, 11.88 [2.32-60.89]; SUCRA, 0.96) and mucosal healing (moderate QoE). Differences in trial design limited comparability of trials of maintenance therapy for efficacy. Vedolizumab was ranked safest in terms of serious adverse events (SUCRA, 0.91), and infection (SUCRA, 0.75) in maintenance trials. Infliximab and vedolizumab are ranked highest as first-line agents, and tofacitinib is ranked highest as second-line agent, for induction of remission and mucosal healing in patients with moderate-severe UC, based on indirect comparisons. Head-to-head trials are warranted to inform clinical decision-making with greater confidence.

Singh S ，Fumery M ，Sandborn WJ ，Murad MH ... -  《-》