{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:19:43Z","timestamp":1793225983755,"version":"4.5.0"},"reference-count":29,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"unspecified","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Arthritis Society of Canada","award":["23-0313"],"award-info":[{"award-number":["23-0313"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,11,7]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors have revolutionized cancer treatment but can induce immune-related adverse events (irAEs), which are sometimes severe, life-threatening, or refractory to corticosteroids. Current management is largely empirical and adapted from autoimmune disease protocols. Dysregulation of the Janus kinase (JAK)\u2013signal transducer and activator of transcription (STAT) pathway has been implicated in irAE pathogenesis, positioning JAK inhibitors (JAKi) as potential therapeutic agents. We hypothesized that JAKi may offer therapeutic benefit in treating corticosteroid-refractory or life-threatening irAEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective cohort study at the Jewish General Hospital (Montreal, Canada) within the Montreal Immune-Related Adverse Events biobank, enrolling patients who developed grade \u22653 or persistent grade 2 irAEs unresponsive to corticosteroids or life-threatening irAEs requiring urgent intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>29 patients received JAKi; 5 were excluded due to death within 30 days of initiation, leaving 24 evaluable patients (median age 69 years; 37.5% female). The majority received anti-programmed cell death protein-1 (PD-1) monotherapy (79.2%), with some receiving combination anti-cytotoxic T-lymphocyte antigen-4\/PD-1 therapy (16.7%). Indications for JAKi use included myocarditis (n=8), arthritis (n=4), colitis (n=3), hepatitis (n=3), encephalitis (n=2), pneumonitis (n=2), myasthenia gravis (n=1), and sicca syndrome (n=1). JAKi were employed as second-line therapy in 7 patients, third-line in 11, and fourth-line or later in 6. Clinical response, defined as irAE resolution to grade \u22641 while on \u226410\u2009mg prednisone equivalent without relapse for \u226530 days, was observed in 17 patients (70.8%), with median time to resolution of 41 days. Response rates were highest for myocarditis (75%) and arthritis (100%). No opportunistic infections or JAKi-related hepatotoxicity occurred; thrombotic events were identified in three individuals (10.3%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that JAKi are a promising, well-tolerated option for managing corticosteroid-refractory or life-threatening irAEs. Further randomized studies are warranted to confirm their efficacy and safety in this setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013214","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T20:35:23Z","timestamp":1764362123000},"page":"e013214","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["JAK inhibitors for the treatment of life-threatening and refractory immune-related adverse events secondary to immune checkpoint inhibitors: a prospective cohort study"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0741-7518","authenticated-orcid":false,"given":"Rami","family":"Habib","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Oncology, Jewish General Hospital, Montreal, Qu\u00e9bec, Canada"},{"name":"McGill University Faculty of Medicine and Health Sciences, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson H","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Oncology, Jewish General Hospital, Montreal, Qu\u00e9bec, Canada"},{"name":"McGill University Faculty of Medicine and Health Sciences, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3004-5298","authenticated-orcid":false,"given":"Theodore","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"McGill University Faculty of Medicine and Health Sciences, Montreal, Qu\u00e9bec, Canada"},{"name":"Department of Medicine, Division of Rheumatology, Jewish General Hospital, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia V","family":"Del Rincon","sequence":"additional","affiliation":[{"name":"McGill University Faculty of Medicine and Health Sciences, Montreal, Qu\u00e9bec, Canada"},{"name":"Department of Medicine, Division of Rheumatology, Jewish General Hospital, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5499-2661","authenticated-orcid":false,"given":"Claudie","family":"Berger","sequence":"additional","affiliation":[{"name":"McGill University Faculty of Medicine and Health Sciences, Montreal, Qu\u00e9bec, Canada"},{"name":"Lady Davis Institute for Medical Research, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel Flores","family":"Molina","sequence":"additional","affiliation":[{"name":"McGill University Faculty of Medicine and Health Sciences, Montreal, Qu\u00e9bec, Canada"},{"name":"Department of Medicine, Division of Rheumatology, Jewish General Hospital, Montreal, Qu\u00e9bec, 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