HLA Alleles May Play a Role in Formation of Anti-Drug Antibodies to Adalimumab

Specific human leukocyte antigen (HLA) alleles are associated with the formation of anti-drug antibodies to adalimumab in patients with rheumatoid arthritis (RA) and hidradenitis suppurativa (HS), potentially causing reduced therapeutic response, according to recent research by Mohan Liu, PhD, and colleagues published online in PLoS One.

Although certain HLA alleles are known to be associated with antibody formation against infliximab, the role of patient-related factors in determining anti-adalimumab antibody formation had not previously been shown. The results suggest that specific HLA alleles may play a key role in developing these antibodies in patients with RA and HS treated with adalimumab, the authors conclude.

The study received funding from AbbVie, maker of reference adalimumab (Humira). Two biosimilar adalimumab products have been approved by the FDA.

The researchers drew their study subjects from participants in 4 different phase 3 clinical trials that enrolled patients with RA or HS at sites predominantly in the United States and Europe. Patients with RA received subcutaneous injections of 40 mg of adalimumab every other week for up to 24 weeks, as well as weekly oral doses of methotrexate; patients with HS received 40 mg subcutaneous adalimumab injections every week or every other week for up to 36 weeks.

Samples from 634 subjects with either RA or HS were analyzed. Of this group, 37 subjects (17 with RA, 20 with HS) developed antibodies to adalimumab during treatment, and 597 subjects (348 with RA, 249 with HS) did not develop these antibodies during the clinical trials.

Using next-generation sequencing-based HLA typing, the researchers identified 3 specific protective HLA alleles that were less prevalent in antibody-positive subjects than in antibody-negative subjects (odds ratios [OR]: 0.4, 0.25, and 0.28, respectively) and 2 risk HLA alleles that were more abundant in antibody-positive than in antibody-negative subjects (OR: 2.52 and 2.64, respectively).

The 3 protective alleles were:

• HLA-DQB1*05
• HLA-DRB1801
• HLA-DRB1*07

The 2 risk alleles were:

• HLA-DRB1*03
• HLA-DRB1*011

The researchers report that HLA-DRB1*03 is independently predictive of antibody formation in patients with RA and HS with adalimumab treatment and in patients with inflammatory bowel disease receiving infliximab treatment. “These results provide additional insight into underlying reasons for variable immunogenicity response across different patients treated with [anti—tumor necrosis factor] therapy,” they conclude.

Reference

Liu M, Degner J, Davis JW, Idler KB, Mostafa N, Waring JF. Identification of HLA-CRB1 association to adalimumab immunogenicity. PLoS One. 2018;13(4):e0195325. doi: 10.1371/journal.pone.0195325.