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Clinical Trial
. 2018 Apr 3;13(4):e0195325.
doi: 10.1371/journal.pone.0195325. eCollection 2018.

Identification of HLA-DRB1 association to adalimumab immunogenicity

Mohan Liu  1 , Jacob Degner  1 , Justin Wade Davis  1 , Kenneth B Idler  1 , Ahmed Nader  2 , Nael M Mostafa  2 , Jeffrey F Waring  1
Affiliations
Clinical Trial

Identification of HLA-DRB1 association to adalimumab immunogenicity

Mohan Liu et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: All authors are affiliated with AbbVie. The following product is under development with AbbVie: HUMIRA (adalimumab). This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Forest plot of AAA formation (auto-antibody to adalimumab) according to the different HLA-DQB and DRB alleles in HS and RA by different tests.
(A) HLA Class II DQB and DRB alleles effect of combined subjects in HS and RA by odds ratio and 95% confidence intervals (CIs) on AAA formation by Fisher’s Exact Test. (B) HLA Class II DQB and DRB alleles effect of combined subjects in HS and RA by odds ratio and 95% confidence intervals (CIs) on AAA formation by Fisher’s Exact Test.
See this image and copyright information in PMC

References

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