From oncology to inflammatory bowel disease: HLA pharmacogenetics informs combination immunotherapy to prevent treatment failure

To the Editor The recent study by Zhang et al. published in the Journal of Crohn’s and Colitis provides a compelling pharmacogenetic analysis of HLA-DQA1*05 subtypes in relation to loss of response (LoR) to anti-tumor necrosis factor (anti-TNF) therapy in inflammatory bowel disease (IBD).1 As researchers in oncology, where immunotherapy resistance and biomarker-driven treatment individualization are central themes, we find this work highly relevant to broader disciplines exploring immune-mediated therapies. The study’s primary strength lies in its scale and clinical granularity. With over 25 000 patients from the UK IBD BioResource, the authors reliably associated HLA-DQA1*05:01 with earlier LoR to infliximab and HLA-DQA1*05:05 with earlier LoR to adalimumab, and these associations persisted in Crohn’s disease and ulcerative colitis. Notably, the differential effect of concomitant immunomodulators depending on HLA subtype is a clinically actionable insight. The proposed treatment algorithm represents a tangible step toward personalized medicine, echoing efforts in oncology to use genetic markers to guide combination therapies and mitigate resistance.