HLA-DRB1*01:03 is associated with increased severity across inflammatory bowel disease (IBD) phenotypes, including Crohn’s disease and ulcerative colitis, according to a UK genotype–phenotype study of 43,762 patients. Carriage of the allele was identified in 2,009 patients (4.6%) and showed consistent links with more aggressive disease behaviour.
HLA-DRB1*01:03 and Severe IBD Outcomes
In Crohn’s disease, HLA-DRB1*01:03 was associated with higher odds of colonic resection (OR: 1.35; 95% CI: 1.07–1.69), perianal disease (OR: 1.65; 95% CI: 1.42–1.92) and increased use of advanced therapy (OR: 1.33; 95% CI: 1.12–1.58). In ulcerative colitis or IBD unclassified, the allele showed stronger associations with colectomy (OR: 1.99; 95% CI: 1.63–2.43), perianal disease (OR: 1.70; 95% CI: 1.27–2.28) and advanced therapy use (OR: 2.17; 95% CI: 1.86–2.52).
The allele was also associated with differences in disease onset patterns, being linked to younger onset in ulcerative colitis or IBD unclassified and older onset in Crohn’s disease.
Earlier Progression and Escalation of Therapy
Time-to-event analyses demonstrated that HLA-DRB1*01:03 carriers experienced earlier disease complications. In Crohn’s disease, the allele was associated with earlier development of perianal disease (HR: 1.61; 95% CI: 1.24–2.07) and earlier need for colonic surgery (HR: 1.43; 95% CI: 1.13–1.82). In ulcerative colitis or IBD unclassified, carriers underwent colectomy earlier (HR: 1.69; 95% CI: 1.33–2.14).
Treatment escalation followed a similar pattern, with earlier initiation of advanced therapies in Crohn’s disease (HR: 1.37; 95% CI: 1.18–1.59) and ulcerative colitis or IBD unclassified (HR: 1.82; 95% CI: 1.53–2.16). Carriers also had a higher risk of advanced therapy failure across IBD phenotypes (HR: 1.23; 95% CI: 1.02–1.50).
Clinical Implications
The findings support HLA-DRB1*01:03 as a genetic marker of severe IBD outcomes across phenotypes rather than disease susceptibility alone. If validated, the allele could help identify patients at higher risk of surgery, rapid progression and treatment failure.
This may support earlier and more intensive monitoring strategies, as well as earlier consideration of advanced therapies in patients with a genetically defined high-risk profile.
Reference
Zhang Q et al.HLA-DRB1*01:03 in patients with inflammatory bowel disease: a genotype–phenotype association study. The Lancet Gastroenterology & Hepatology. 2026;DOI:10.1016/S2468-1253(26)00113-5.
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