Safety of Janus kinase inhibitors in immune-mediated inflammatory diseases-a systematic literature review informing the 2024 update of an international expert consensus statement.

Abstract

Objectives: This systematic literature review (SLR) on safety outcomes was performed to inform the 2024 update of the expert consensus statement on the treatment of immune-mediated inflammatory diseases (IMIDs) with Janus kinase inhibitors (JAKi).

Methods: An update of the 2019 SLR was performed in MEDLINE, Embase, and the Cochrane Library. For safety, randomised, placebo-controlled or active-controlled trials on all JAKi investigated in IMIDs, long-term extension (LTE) studies, pooled trial data analyses, and cohort and claims studies were included.

Results: We screened 13,905 records, of which 209 were finally included. Three safety trials and 13 post hoc analyses, 83 efficacy randomised controlled trials (RCTs) with adequate safety reporting, 56 integrated safety analyses and LTE of RCTs, 20 additional conference abstracts on RCT data, as well as 37 real-world cohort studies were presented to the task force. Safety profiles of JAKi were overall consistent across compounds and indications, but impacts of patient profiles, treatment dosing, and other cofactors like background medications on drug safety could be observed. Furthermore, differential effects of variously selective JAKi on distinct adverse events of special interest (AESI) and laboratory outcomes were discerned.

Conclusion: A substantial amount of literature was published on JAKi safety since 2019. A comprehensive overview of these data supports the optimal use of JAKi in patients with IMIDs, by consideration and balance of their benefits as well as risks in every patient.