HLA-DQA1*05 Variant Associated With Immunogenicity Risk for Anti-Infliximab (IFX)/Anti-Adalimumab (ADL) Antibodies

This test identifies the HLA-DQA1*05 variant. Carriers of this variant allele in either one copy (heterozygous) or two copies (homozygous) have a 75% higher risk of anti-infliximab (anti-IFX) or anti-adalimumab (anti-ADL) antibodies compared with noncarriers (relative risk for carriers, 1.75, 95% Cl, 1.37-2.25, according to Solitano et al in the latest systematic review and meta-analysis of 13 studies, including 3,756 patients for a median follow-up of 12 months).¹

Noncarrier patients still developed immunogenicity, albeit at a lower incidence (20% vs 35%).¹ Based on a 41% prevalence of variants (as found in predominantly Europeans and North Americans), a positive result on this test carries a positive predictive value (PPV) for immunogenicity of 30%. A negative result on this test indicates noncarrier status and does not mean the patient cannot develop anti-IFX or anti-ADL; it only suggests that the patient may be at decreased risk, with a negative predictive value (NPV) for immunogenicity of 80%.

The use of concomitant immunosuppressive therapy mitigates but does not eliminate the risk of immunogenicity in both HLA-DQA1*05 variant carriers and noncarriers.¹ In two cohorts where proactive therapeutic drug monitoring (TDM) in infliximab (IFX) or adalimumab (ADL) was routinely performed, the presence of the HLA-DQA1*05 variant was not associated with increased risk of immunogenicity.^2,3