Janus kinase inhibition in juvenile idiopathic arthritis

The introduction of biologics targeting proinflammatory cytokines (eg, tumour necrosis factor [TNF] and interleukin-6) has revolutionised the care of children with juvenile idiopathic arthritis. 1 Stoll ML Cron RQ Treatment of juvenile idiopathic arthritis: a revolution in care. Pediatr Rheumatol Online J. 2014; 12: 13 Crossref PubMed Scopus (111) Google Scholar More recently, small molecule inhibitors of Janus kinases (JAKs) have shown efficacy in treating adult patients with rheumatoid arthritis. 2 Sepriano A Kerschbaumer A Bergstra SA et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2023; 82: 107-118 Crossref PubMed Scopus (18) Google Scholar Given positive clinical trial results in adults, JAK inhibitors are now being explored for use in children with juvenile idiopathic arthritis. JAK inhibitors work by disrupting intracellular signalling pathways (via the signal transducer and activator of transcription, or JAK-STAT, pathway) downstream of receptors shared by multiple cytokines. Tofacitinib, which is primarily an inhibitor of JAK1 and JAK3, has already shown efficacy in the treatment of polyarticular course juvenile idiopathic arthritis. 3 Ruperto N Brunner HI Synoverska O et al. Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial. Lancet. 2021; 398: 1984-1996 Summary Full Text Full Text PDF PubMed Scopus (55) Google Scholar Baricitinib in juvenile idiopathic arthritis: an international, phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trialBaricitinib was efficacious with an acceptable safety profile in the treatment of polyarticular juvenile idiopathic arthritis, extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, and juvenile psoriatic arthritis, after inadequate response or intolerance to standard therapy. Full-Text PDF