A large-scale comparison of clinical outcomes to IBD therapies in White and South Asian ethnicities.

Background: While ethnic differences in IBD phenotype are recognised, the comparative efficacy and safety of common IBD therapies across ethnically diverse populations remain uncertain. This multicentre cohort study aimed to compare the efficacy and safety of these therapies between White (WH) and South Asian (SA) IBD cohorts. Methods: Demographic, phenotypic and outcome data from the UK IBD BioResource were utilised (BioResource inception date: 1st January 2016; data lock for analysis: 12th May 2023). The primary outcome was treatment response (defined as treatment persistence free of discontinuation or failure) to 5-aminosalicylates (5-ASAs), thiopurines and anti-TNFs. The secondary outcome was the occurrence of treatment-related adverse events (AEs). Ethnic differences in treatment response were evaluated using propensity score weighting and Cox proportional hazards regression. AE occurrence was assessed through logistic regression analysis. Findings: In total, 26,530 patients were included [51.2% females; median age at diagnosis 30 years (IQR 21-43); 96.1% WH, 3.9% SA]. SA were diagnosed at a younger age, began treatment younger than WH, and demonstrated baseline phenotypic differences including more perianal disease in CD. However, no significant differences in treatment response between WH and SA were identified in either CD (reference group WH; thiopurines, HR 0.82 (95% CI 0.53-1.27), p = 0.37; anti-TNFs, HR 1.07 (95% CI 0.34-3.37), p = 0.91] or UC [thiopurines, HR 0.98 (95% CI 0.95-1.02), p = 0.36; anti-TNFs, HR 0.98 (95% CI 0.92-1.04), p = 0.54]. SA were at significantly increased risk of pancreatitis [HR 2.34 (95% CI 1.37-3.75), p = 0.001] and leucopenia [HR 1.76 (95% CI 1.02-2.84), p = 0.03] with thiopurines, and renal dysfunction with anti-TNFs [HR 4.75 (95% CI 1.55-12.07), p = 0.002]. Interpretation: Treatment efficacy in similar WH and SA IBD patients recruited to the UK IBD BioResource is unaffected by ethnicity but patients from SA ethnic backgrounds are at increased risk of developing pancreatitis and leucopenia with thiopurines, and renal dysfunction with anti-TNFs. These findings highlight the importance of comprehensive risk assessment and counselling by clinicians, and emphasise the importance of improving ethnic representation in IBD research. Funding: Bowel Research UK; NIHR Imperial Biomedical Research Centre (BRC); NIHR Cambridge BRC.