Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a systematic literature research

Objectives Review of efficacy and safety of Janus kinase (JAK) inhibition in immune-mediated inflammatory diseases (IMIDs). Methods A systematic literature research (SLR) of all publications on JAK inhibitors (JAKi) treatment published until March 2019 using MEDLINE, EMBASE and the Cochrane Library. Efficacy and safety were assessed in randomised controlled trials (RCTs), integrating long-term extension periods additionally for safety evaluation. Results 3454 abstracts were screened with 85 included in the final analysis (efficacy and RCT safety: n=72; safety only: n=13). Efficacy of RCTs investigating tofacitinib (TOFA, n=27), baricitinib (BARI, n=9), upadacitinib (UPA, n=14), filgotinib (FILGO, n=7), decernotinib (DEC, n=3) and peficitinib (PEF, n=7) was evaluated. Six head-to-head trials comparing JAKi with tumour necrosis factor inhibitors (TNFi) were included. Efficacy of JAKi was shown in rheumatoid arthritis (RA) for all agents, psoriatic arthritis (TOFA, FILGO), ankylosing spondylitis (TOFA, FILGO), systemic lupus erythematosus (BARI), chronic plaque psoriasis (TOFA, BARI, PEF), ulcerative colitis (TOFA, UPA), Crohn's disease (UPA, FILGO) and atopic dermatitis (TOFA, BARI, UPA). Safety analysis of 72 RCTs, one cohort study and 12 articles on long-term extension studies showed increased risks for infections, especially herpes zoster, serious infections and numerically higher rates of venous thromboembolic events. No increased malignancy rates or major adverse cardiac events were observed. Conclusion JAKi provide good efficacy compared to placebo (and to TNFi in RA and Pso) across various IMIDs with an acceptable safety profile. This SLR informed the task force on points to consider for the treatment of IMIDs with JAKi with the available evidence.