Gene variant flags high-risk IBD patients early

Clinical Takeaway: Consider HLA-DRB1*01:03 an emerging risk marker for more aggressive IBD, but not yet a stand-alone tool for treatment selection pending validation and clinical utility studies.

A readily testable HLA marker could help identify patients who may need closer monitoring or earlier advanced therapy before severe complications develop.

In the largest genotype–phenotype study of IBD to date, researchers analyzed 43,762 UK patients with IBD, including 21,839 with Crohn’s disease and 21,923 with ulcerative colitis or IBD unclassified. HLA-DRB1*01:03 was present in 2,009 patients (4.6%) and was associated with a broad pattern of more severe disease.

Among patients with Crohn’s disease, carriage was linked to higher odds of perianal disease (odds ratio [OR], 1.65), colonic surgery (OR, 1.35), and advanced therapy use (OR, 1.33). Among patients with ulcerative colitis or IBD unclassified, the allele was associated with colectomy (OR, 1.99), hospitalization (OR, 1.96), perianal disease (OR, 1.70), and advanced therapy use (OR, 2.17). Time-to-event analyses also suggested earlier onset of major outcomes, including perianal Crohn’s disease (hazard ratio [HR], 1.61), Crohn’s colonic surgery (HR, 1.43), colectomy in ulcerative colitis or IBD unclassified (HR, 1.69), and first advanced therapy use.

Carriers were also more likely to discontinue first advanced therapy for primary nonresponse or loss of response (HR, 1.23), particularly anti-TNF therapy and JAK inhibitors.

“This study brings us one step closer to personalized medicine,” co-senior author Professor James Lee said.

The authors cautioned that further validation is needed, particularly in non-European populations and to assess cost-effectiveness, predictive performance, and implementation feasibility.

Source: Zhang Q, et al. (2026, June 15). Lancet Gastroenterol Hepatol. HLA-DRB1*01:03 in patients with inflammatory bowel disease: a genotype-phenotype association study