Janus-kinase inhibitor use in immune-mediated inflammatory diseases beyond licensed indications: A scoping review

Introduction: The use of Janus kinase inhibitors (JAKis) in immune-mediated inflammatory diseases (IMIDs) beyond licence is expanding rapidly. The aim of this scoping review was to identify and present the available evidence on the efficacy of JAKis in all conditions without marketing authorisation. Methods: Through a systematic literature search we identified studies including 5 or more patients that assessed the use of any JAKi for any efficacy outcome. Quantitative analyses in the form of pairwise meta-analyses were performed for eligible data from randomised controlled trials (RCTs) only. Results: Eighty-three (n = 83) studies in total were included in our review, assessing efficacy of JAKis in 34 IMIDs. In most conditions, JAKis exhibited generally positive effects, though the majority of evidence came from observational, non-comparative studies. Pairwise meta-analyses were possible for hidradenitis suppurativa and systemic lupus erythematosus (SLE). For hidradenitis suppurativa, we found a clear benefit of treatment with JAKis compared with placebo in achieving clinical response [OR 2.35, 95 % CI (1.24 to 4.46)]. For treatment- resistant SLE, the results were equivocal; JAKi showed some benefit over placebo but statistical significance was only reached for one of the two meta-analysed outcome measures [SLE Responder Index 4, OR 1.41, 95 % CI (1.01 to 1.98); SLE Disease Activity Index 2000; OR 1.36, 95 % CI (0.99 to 1.88)]. Conclusions: There is a rapidly increasing use of JAKis beyond current licencing in most IMIDs. Large comparative trials are necessary to confirm efficacy and guide future licencing decisions.