Hypersensitivity Associated with IL-1 and IL-6 Inhibitors Links to Common HLA Alleles

Researchers at Stanford and UCSF have discovered a strong association between serious, potentially fatal, delayed hypersensitivity reactions that occur in a subset of patients exposed to IL-1/IL-6 inhibitors and HLA-DRB1*15 alleles that are common across ancestries. Anti-IL-1/6 therapies are commonly used to treat inflammatory conditions and this finding suggests that HLA testing before prescription, treatment monitoring, and applicable drug safety labeling could improve safety. Misinterpreted as disease flares, Drug reaction with eosinophilia and systemic symptoms (DRESS), a severe delayed hypersensitivity reaction (DHR), often goes unrecognized in patients with inflammatory illness. Unusual clinical features including severe drug-associated lung disease and rash arising during IL-1 and IL-6 inhibitor treatment of Still's and Still's-like disease across the age spectrum [systemic onset juvenile arthritis (sJIA) and adult onset Stills disease (AOSD)] suggested this serious DHR to the researchers. See publication of Saper and Mellins et al. for more information on their multi-center, retrospective study of a convenience sample of IL-1 or IL-6 inhibitor-exposed cases of Still's and Kawasaki disease.

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