A large, prospective UK study found that two commonly prescribed biologic drugs—abatacept and adalimumab—demonstrated similar effectiveness in patients with rheumatoid arthritis, regardless of genetic background.

Specifically, no significant difference in treatment outcomes was observed based on the presence of two genetic variants that are linked to rheumatoid arthritis (RA) susceptibility: the HLA-DRB1 shared epitope (SE) or valine at position 11 (Val11).

The findings came from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS), a nationwide cohort of 342 patients with RA from 53 UK centers. Participants were followed for up to 12 months after initiating either abatacept or adalimumab. Led by Chuan Fu Yap, PhD, of The University of Manchester, the researchers used genetic testing, clinical response assessments, and serum drug level measurements to evaluate associations between genotype and treatment response.

Abatacept modulates T-cell activation, while adalimumab is a tumor necrosis factor inhibitor. Despite their differing mechanisms, the researchers found no difference in effectiveness—as measured by European League Against Rheumatism (EULAR) response—remission rates (DAS28 < 2.6), or changes in disease activity scores.

In a genetic analysis, the authors assessed whether carrying zero, one, or two copies of SE or Val11 affected treatment response. They found a weak association between Val11 copy number and EULAR response, but this effect was not drug-specific. No statistically significant interaction was observed between genotype and treatment type.

In a subgroup analysis of patients who were biologic-naïve, those with SE or Val11 alleles were slightly more likely to achieve remission with abatacept than with adalimumab. However, this observation was based on small sample sizes and was not consistent across other response measures. The researchers noted that these findings require confirmation in larger, independent studies.

The study also adjusted for confounding variables that are known to affect treatment response, including age, sex, body mass index, methotrexate use and adherence, drug levels, and comorbidities. Patients treated with abatacept were generally older, had longer disease duration, and were more likely to have used prior biologics. Adjusting for these factors revealed no consistent genetic advantage for either drug.

Biologic-naïve status and achieving therapeutic drug levels emerged as stronger predictors of response than genetic markers. Patients who were new to biologic therapy and had adequate drug levels were more likely to achieve remission and favorable EULAR scores.

While earlier studies hinted at improved outcomes with abatacept in patients who were SE-positive, this larger real-world cohort does not support genotype-based prescribing for these biologics, and the researchers concluded that current genetic markers may not be suitable for guiding personalized treatment decisions between abatacept and adalimumab in RA management.

Full disclosures can be found in the published study.

Source: Arthritis and Rheumatology