Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 26.
doi: 10.1002/art.43298. Online ahead of print.

Comparative Effectiveness of Abatacept Versus Adalimumab in Shared Epitope Positive and Negative Patients With Rheumatoid Arthritis

Chuan Fu Yap  1 , Nisha Nair  2 , Seema D Sharma  1 , John Bowes  1 , Amirah Binti Mohammad Ariff  1 , Ann W Morgan  3 , John D Isaacs  4 , Anthony G Wilson  5 , Kimme L Hyrich  6 , Suzan Verstappen  6 , James Bluett  2 , Andrew P Morris  2 , Anne Barton  2 , Darren Plant  2 , Sebastien Viatte  7
Affiliations
Free article

Comparative Effectiveness of Abatacept Versus Adalimumab in Shared Epitope Positive and Negative Patients With Rheumatoid Arthritis

Chuan Fu Yap et al. Arthritis Rheumatol. .
Free article

Abstract

Objective: The effect of the shared epitope (SE) and valine at position 11 (Val11) of HLA-DRB1 on the activation of CD4+ T cells is expected to be diminished by abatacept, a costimulation blocker. However, published evidence on the value of genetic stratification for abatacept treatment is conflicting. We aimed to compare the difference in effectiveness of abatacept and adalimumab in patients carrying the SE (or Val11).

Methods: The Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate is a nationwide observational cohort study recruiting patients from 53 centers across the United Kingdom before the initiation of biologic treatment and following them up prospectively for 12 months. Three hundred forty-two patients starting either abatacept or adalimumab were eligible for this analysis. Serum drug levels for abatacept, adalimumab, and methotrexate were determined at multiple time points. Multivariate modeling integrating demographic, clinical, and pharmacological variables was used to test for associations between the number of copies of the SE or Val11 and response to treatment (EULAR response; Disease Activity Score in 28 joints [DAS28] remission; change in DAS28). Differential effectiveness between drugs and genetic markers was assessed by the significance of their interaction term.

Results: There was no difference in the efficacy of abatacept versus adalimumab. We found weak evidence for an independent association of genetic markers with response to treatment (Val11 with EULAR response: P = 0.02), but there was no significant difference in this effect between drugs.

Conclusion: We found no evidence that HLA typing is clinically useful to support prescription decisions for these two drugs.

PubMed Disclaimer

References

REFERENCES

    1. Wei M, Chu CQ. Prediction of treatment response: personalized medicine in the management of rheumatoid arthritis. Best Pract Res Clin Rheumatol 2022;36(1):101741.
    1. James EA, Rieck M, Pieper J, et al. Citrulline‐specific Th1 cells are increased in rheumatoid arthritis and their frequency is influenced by disease duration and therapy. Arthritis Rheumatol 2014;66(7):1712–1722.
    1. Law SC, Street S, Yu CHA, et al. T‐cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis patients carrying HLA‐DRB1 shared epitope alleles. Arthritis Res Ther 2012;14(3):R118.
    1. Moon JS, Younis S, Ramadoss NS, et al. Cytotoxic CD8+ T cells target citrullinated antigens in rheumatoid arthritis. Nat Commun 2023;14(1):319.
    1. Han B, Diogo D, Eyre S, et al. Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity. Am J Hum Genet 2014;94(4):522–532.

LinkOut - more resources