Identification of HLA-DRB1 association to adalimumab immunogenicity

• Published in: PloS one Vol. 13; no. 4; p. e0195325
• Main Authors: Liu, Mohan, Degner, Jacob, Davis, Justin Wade, Idler, Kenneth B., Nader, Ahmed, Mostafa, Nael M., Waring, Jeffrey F.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.04.2018; Public Library of Science (PLoS)
• Subjects: Adalimumab; Adalimumab - immunology; Adalimumab - therapeutic use; Alleles; Analysis; Anti-Inflammatory Agents - immunology; Anti-Inflammatory Agents - therapeutic use; Antibodies; Antigens; Antirheumatic Agents - immunology; Antirheumatic Agents - therapeutic use; Arthritis; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Autoantibodies; Biology and Life Sciences; Clinical trials; Dosage and administration; Drb1 protein; Drug dosages; Drug therapy; Genomics; Health aspects; Hidradenitis Suppurativa - blood; Hidradenitis Suppurativa - drug therapy; Hidradenitis Suppurativa - genetics; Hidradenitis Suppurativa - immunology; Histocompatibility antigen HLA; Histocompatibility Testing; HLA antigens; HLA-DQ beta-Chains - blood; HLA-DQ beta-Chains - genetics; HLA-DRB1 Chains - genetics; Humans; Immunogenicity; Immunoglobulins; Immunotherapy; Infliximab; Interferon; Medical research; Medicine and Health Sciences; Monoclonal antibodies; Multiple sclerosis; Patients; Pharmacogenomic Variants; Philosophy of science; Physiological aspects; Research and Analysis Methods; Rheumatoid arthritis; Sequence Analysis; Skin diseases; Tissue typing; TNF inhibitors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Values; United States > US; North Chicago Illinois
• DOI: 10.1371/journal.pone.0195325
• ISSN: 1932-6203

Anti-drug antibody formation occurs with most biological agents across disease states, but the mechanism by which they are formed is unknown. The formation of anti-drug antibodies to adalimumab (AAA) may decrease its therapeutic effects in some patients. HLA alleles have been reported to be associated with autoantibody formation against interferons and other TNF inhibitors, but not adalimumab. We analyzed samples from 634 subjects with either rheumatoid arthritis (RA) or hidradenitis suppurativa (HS): 37 subjects (17 RA and 20 HS) developed AAA (AAA+) during adalimumab treatment and 597 subjects (348 RA, 249 HS) did not develop AAA (AAA-) during the clinical trials. Using next-generation sequencing-based HLA typing, we identified three protective HLA alleles (HLA-DQB1*05, HLA-DRB1*01,and HLA-DRB1*07) that were less prevalent in AAA+ than AAA-subjects (ORs: 0.4, 0.25 and 0.28, respectively; and P values: 0.012, 0.012 and 0.018, respectively) and two risk HLA alleles (HLA-DRB1*03 and HLA-DRB1*011) that were more abundant in AAA+ than AAA-subjects (ORs: 2.52, and 2.64, respectively; and P values: 0.006 and 0.019). Similar to the finding of Billiet et al. who found that carriage of the HLA-DRB1*03 allele was more prevalent in those with anti-infliximab antibodies (OR = 3.6, p = 0.002, 95% CI: [1.5,8.6]).), we found HLA-DRB1*03 allele was also more prevalent in anti-adalimumab positive (OR = 2.52, p = 0.006, 95% CI: [1.37,4.63]). The results suggest that specific HLA alleles may play a key role in developing AAAs in RA and HS patients treated with adalimumab.