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. 2025 Jun 30:keaf356.
doi: 10.1093/rheumatology/keaf356. Online ahead of print.

The therapeutic potential for JAK inhibitors for immune-related adverse events from checkpoint inhibitors- a review of the literature

Deepak Nagra  1   2 , Kaiyang Song  1 , Joy Odia  2 , Chris Wincup  1   3 , Arti Mahto  3 , Chamith Rosa  2 , Ganesh Kasavkar  2 , Maryam A Adas  1 , Zijing Yang  1 , Mark D Russell  1 , Katie Bechman  1 , Tim Blake  2 , Siwalik Banerjee  2 , Nicola Gullick  2 , James B Galloway  1
Affiliations

The therapeutic potential for JAK inhibitors for immune-related adverse events from checkpoint inhibitors- a review of the literature

Deepak Nagra et al. Rheumatology (Oxford). .

Abstract

Objectives: The role of JAK inhibitors in immune mediated adverse events were not included in the EULAR 2021 guidance on the management of rheumatic immune-related adverse events from checkpoint inhibitors or the society of immunotherapy of cancer guidelines on this topic. We aim to describe the role of JAK inhibitors for the management of immune mediated adverse events with a review of case reports.

Methods: Pubmed, EMBASE and MEDLINE searches were performed from inception till 25 May 2025 for case reports/series of the use of JAK inhibitors to treat checkpoint inhibitor induced immune adverse events. Five EMA licenced JAK inhibitors (tofacitinib, baritinib, upadacitinib, filgotinib and ruxolitinib) were included in addition to peficitinib. The 11 FDA approved checkpoint inhibitors were included.

Results: Published Case reports, case series and cohort data included 104 patient's. Most patients received tofacitinib (82%). Pembrolizumab monotherapy represented the most common immune checkpoint inhibitor. The commonest cancers were Lung (20%), followed by gastric (17%) and metastatic melanoma (16%). The indication for JAK inhibitor therapy for irAE's was predominantly myocarditis (70%), followed by myositis (33%) and hepatitis (24%). Tumour progression was observed in 38% of patients, with 14% remaining in remission. Across all patients, 4% died due to progression of their cancer.

Conclusion: JAK inhibitors are emerging as a promising option for the treatment of immune checkpoint inhibitor-related toxicities. The currently published evidence, primarily from case reports and case series, suggests they have efficacy, particularly in patients who have failed to respond to other cytokine inhibition strategies.

Keywords: JAK inhibitor; arthritis; cancer; checkpoint inhibitor; cytokines; immune-mediated; immunotherapy; myositis; pembrolizumab.

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