Background and aims: Identifying patients at high risk of immunogenicity is important when selecting tumor necrosis factor-(TNF)α antagonists in patients with immune-mediated inflammatory diseases (IMIDs). We evaluated the association HLA-DQA1*05 genotype and risk of immunogenicity with TNFα antagonists. Methods: Through a systematic review till 14 July, 2022, we identified studies in patients with IMIDs treated with TNFα antagonists, which reported the risk of immunogenicity and/or secondary loss of response in patients with HLA-DQA1*05 variants. Primary outcome was risk of immunogenicity. We performed random effects meta-analysis and used GRADE to appraise certainty of evidence. Results: On meta-analysis of 13 studies (3,756 patients, median follow-up, 12m; 41% with variants), HLA-DQA1*05 variants were associated with 75% higher risk of immunogenicity compared to wild type [relative risk (RR), 1.75 (95% CI, 1.37-2.25)] with considerable heterogeneity (I2=62%) (low certainty evidence). Positive and negative predictive value of HLA-DQA1*05 variants for predicting immunogenicity was 30% and 80%, respectively. Proactive therapeutic drug monitoring, but not concomitant use of IMMs, IMIDs- and TNFα antagonist-type, modified this association. Patients with HLA-DQA1*05 variants experienced 2.2-fold higher risk of secondary loss of response [six cohorts; RR, 2.24 (1.67-3.00), I2=0%] (moderate certainty evidence). Conclusion: Variants in HLA-DQA1*05 are associated with an increased risk in immunogenicity and secondary loss of response in patients with IMIDs treated with TNFα antagonists. However, the positive and negative predictive value is moderate, and decisions on concomitant use of IMMs to prevent immunogenicity should be individualized based on all factors that influence drug clearance.
HLA-DQA1*05 Genotype and Immunogenicity to Tumor Necrosis Factor-α Antagonists: A Systematic Review and Meta-analysis
Facciorusso, Antonio;
2023-01-01
Abstract
Background and aims: Identifying patients at high risk of immunogenicity is important when selecting tumor necrosis factor-(TNF)α antagonists in patients with immune-mediated inflammatory diseases (IMIDs). We evaluated the association HLA-DQA1*05 genotype and risk of immunogenicity with TNFα antagonists. Methods: Through a systematic review till 14 July, 2022, we identified studies in patients with IMIDs treated with TNFα antagonists, which reported the risk of immunogenicity and/or secondary loss of response in patients with HLA-DQA1*05 variants. Primary outcome was risk of immunogenicity. We performed random effects meta-analysis and used GRADE to appraise certainty of evidence. Results: On meta-analysis of 13 studies (3,756 patients, median follow-up, 12m; 41% with variants), HLA-DQA1*05 variants were associated with 75% higher risk of immunogenicity compared to wild type [relative risk (RR), 1.75 (95% CI, 1.37-2.25)] with considerable heterogeneity (I2=62%) (low certainty evidence). Positive and negative predictive value of HLA-DQA1*05 variants for predicting immunogenicity was 30% and 80%, respectively. Proactive therapeutic drug monitoring, but not concomitant use of IMMs, IMIDs- and TNFα antagonist-type, modified this association. Patients with HLA-DQA1*05 variants experienced 2.2-fold higher risk of secondary loss of response [six cohorts; RR, 2.24 (1.67-3.00), I2=0%] (moderate certainty evidence). Conclusion: Variants in HLA-DQA1*05 are associated with an increased risk in immunogenicity and secondary loss of response in patients with IMIDs treated with TNFα antagonists. However, the positive and negative predictive value is moderate, and decisions on concomitant use of IMMs to prevent immunogenicity should be individualized based on all factors that influence drug clearance.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
