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

Objective: This systematic literature review (SLR) on efficacy 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 efficacy, randomised, placebo (PLC)- or active-controlled trials on all JAKi investigated in IMIDs, as well as cohort and claims data for conditions where such studies were not available, were included.

Results: In total, 10,556 records were screened, and 182 articles were included in the final analysis, investigating 21 JAKi in 51 IMIDs. Forty-three phase 2 and 59 phase 3 trials as well as 9 strategic trials and 72 pilot or cohort studies and case series were considered. JAKi demonstrated efficacy both in PLC-controlled trials as well as in head-to-head comparisons against active comparators, with 93 of 102 randomised controlled trials (RCTs) meeting their primary endpoints. Since 2019, 8 JAKi have received approval by the Federal Drug Agency and the European Medicine Agency for treatment of 11 IMIDs; of these, for 2, no approved disease-modifying antirheumatic drug (DMARD) therapy had previously been available.

Conclusions: JAKi are effective for treating IMIDs, and various compounds have recently been approved. The impact of Janus kinase (JAK) selectivity for distinct JAK-STAT pathways needs further investigation, and few data are also available on sustained disease control upon tapering or withdrawal or on the optimal strategic placement of JAKi in international treatment algorithms.