V Solitano et al. Clin Gastroenterol Hepatol 2023; 21: 3019-3029. HLA-DQA1∗05 Genotype and Immunogenicity to Tumor Necrosis Factor-α Antagonists: A Systematic Review and Meta-analysis

Key findings:

• On meta-analysis of 13 studies (3756 patients; median follow-up, 12 months; 41% with variants), HLA-DQA1∗05 variants were associated with 75% higher risk of immunogenicity compared with non-carriers (relative risk, 1.75) with considerable heterogeneity (I² = 62%) (low certainty evidence).
• In addition, patients with HLA-QQA1*05 variants had clinical loss of response (LOR) in 67% compared to 30% in those without this variant (wild-type); thus, a 124% higher risk of LOR.
• Positive and negative predictive values of HLA-DQA1∗05 variants for predicting immunogenicity were 30% and 80%, respectively
• Proactive therapeutic drug monitoring, but not concomitant use of IMMs, IMIDs, and TNF-α antagonist-type, modified this association.

My take:

• The ~40% of individuals with HLA-DQA1*05 variants are at higher risk of LOR and are more likely to benefit from both therapeutic drug monitoring and probably from use of combination (with immunomodulator) therapy.
• The positive predictive value (30%) is low indicating that the majority of patients with these variants will not develop anti-drug antibodies within 12 months.
• In those with negative testing for HLA-DQA1*05 (~60%), the higher negative predictive value indicates a patient is more likely to do well with monotherapy.
• HLA-DQA1*05 testing is available commercially (usually part of Celiac HLA typing).

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