Human-leukocyte antigen type is associated with duration on infliximab therapy in patients with antibodies to infliximab

Inc.). Patient and therapy factors and the number of allele carriers for the different DRB1 alleles were compared between cases and controls. Stepwise logistic regression was performed to identify independent predictors of ATI formation. Results At IFX start, a loading dose (at weeks 0-2-6) and a higher albumin level were protective for ATI formation (P<0.05, Chi2 and Mann Whitney test). When considering the total number of DRB1 alleles, we found that 13% of the alleles in cases were DRB1*03 positive compared to 4% in the control group (P=0.02 (adjusted for multiple testing with FDR); OR=3.7, 95% CI 1.6-8.7). This association was independent of disease type, use of a loading dose or concomitant immunomodulator use (P<0.01; Cochran Mantel Haenszel). In a multiple logistic regression model, the presence of DRB1*03, absence of a loading dose and IFX monotherapy were independent significant predictors of ATI formation with OR (95%CI) of 6.7 (2.3-19.5), 2.9 (1.4-6.3) and 2.02 (1.0-4.2) respectively. Conclusions We demonstrate that ATI formation is influenced by the HLA-DRB1 locus in patients with IBD. This locus has already been associated with formation of antibodies to interferon beta therapy in multiple sclerosis and the DRB1*03 allele with formation of anti-Ro/La antibodies in lupus. Our results therefore further implicate a causal role for this allele group in immunogenicity. We also demonstrated that low serum albumin and absence of a loading dose are involved in ATI formation. Low albumin has previously been linked to ATI formation and might be a surrogate marker for disease burden and an aggravated immune response. The absence of a loading dose has not been previously implicated in ATI formation. Although this loading dose is now applied widely, we feel our findings are clinically important.