January 14, 2020
Do genetics play a role in the formation of anti-TNF antibodies?
Genetic risk factors may help to identify patients at higher risk of immunogenicity. This may help clinicians to target combination therapy, or other strategies to avoid sensitization.
Sazonovs A, Kennedy NA, Moutsianas L, et al. HLA-DQA1*05 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn’s Disease. Gastroenterol. 2020;158(1):189–99; https://doi.org/10.1053/j.gastro.2019.09.041
To identify genetic risk factors for developing antibodies against anti-tumor necrosis factor (anti-TNF) agents, researchers in the United Kingdom analyzed genomic data and clinical outcomes from 1,240 patients with Crohn’s disease starting treatment with infliximab or adalimumab as part of multicenter cohort study. The authors used an enzyme-linked assay to measure anti-drug antibody levels, defining immunogenicity as a titer ≥10 absorbance units (AU) per milliliter.
The analysis revealed that 44% of all patients in the cohort developed anti-drug antibodies within one year of treatment. However, those with the HLA-DQA1*05 allele were 90% more likely to develop immunogenicity than those without this allele (Hazard Ratio [HR], 1.90; 95% Confidence Interval [CI], 1.60–2.25; P<0.05). The highest rates of immunogenicity were seen among infliximab monotherapy recipients with the HLA-DQA1*05 allele, 92% of whom had evidence of immunogenicity within one year of treatment initiation. In contrast, 10% of those who did not carry HLA-DQA1*05 and were treated with adalimumab combination therapy developed immunogenicity within one year.
While the risk of immunogenicity was highest among HLA-DQA1*05 carriers receiving infliximab monotherapy, rates of immunogenicity were still roughly doubled by the presence of the allele among patients who received an anti-TNF in combination with an immunomodulator.
The authors validated their findings prospectively in a separate cohort of patients with Crohn’s disease.
Study Design: Prospective observational cohort
Funding: CORE, the British Society of Gastroenterology, AbbVie Inc., Merck Sharp & Dohme Ltd., NAPP Pharmaceuticals Ltd., Pfizer Ltd., Celltrion Healthcare, and Cure Crohn’s Colitis.
Allocation: Not applicable
Level of Evidence: 2b (Oxford Levels of Evidence)