Antidrug Antibodies Associated With Biologic Drug Response in Rheumatoid Arthritis

Antidrug antibodies are associated with a lack of response to biologic disease-modifying antirheumatic drugs (bDMARDs) among patients with rheumatoid arthritis (RA), highlighting the importance of monitoring these antibodies during treatment management, according study results published in JAMA Network Open.

Investigators assessed the relationship between antidrug antibodies and response to bDMARDs among patients with RA.

A cohort study was conducted utilizing data from the multicentric, open, prospective Anti-Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance to Minimize the Risk of Immunization in RA Patients study (ClinicalTrials.gov Identifier: NCT02116504). Adult patients with a diagnosis of RA according to 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria who were initiating a new bDMARD were included in the analysis.

The primary study outcome was the correlation between the presence of antidrug antibodies and 12-month EULAR treatment response. Secondary outcomes included 6-month EULAR treatment response, as well as responses from subsequent study visits from months 6 to 15 through 18. 

A total of 230 patients were included in the analysis. Mean age was 54.3 years and 77% were women.

At the 12-month mark, the percentage of patients who tested positive for antidrug antibodies was 38.2% among those treated with anti-tumor necrosis factor monoclonal antibodies (anti-TNF mAbs), 6.1% among those taking etanercept, 50.0% among those taking rituximab, and 20.0% among those taking tocilizumab.

According to univariate analysis, an inverse relationship was found between antidrug antibody positivity and EULAR response at the 12-month mark for all bDMARDs (odds ratio [OR], 0.19; 95% CI, 0.09-0.38; P <.001)).

Generalized estimating equation models confirmed this inverse association for all bDMARDs (OR, 0.35; 95% CI, 0.18-0.65; P <.001) for all visits from month 6 onward.

An inverse association between antidrug antibody positivity and EULAR response was also found for tocilizumab, when drugs were analyzed individually (OR, 0.18; 95% CI, 0.04-0.83; P =.03). The results for individual analyses of other drugs were not statistically significant.

Antidrug antibody positivity (OR, 0.41; 95% CI, 0.20-0.83; P =.048), body mass index of at least 25 kg/m² (OR, 0.35; 95% CI, 0.18-0.66; P =.02), and rheumatoid factor positivity (OR, 0.42; 95% CI, 0.20-0.87; P = .02) were all independently inversely associated with response to treatment.

Patients who tested negative for antidrug antibodies had higher drug concentrations of anti-TNF mAbs compared with those who tested positive (mean difference, -9.6 mg/L; 95% CI, -12.4 to -6.9 mg/L; P < .001).

In contrast, drug concentrations for etanercept and adalimumab were lower among patients who withdrew from the study or switched drug treatments (etanercept: 1.8 mg/L; 95% CI, 1.4-2.2 mg/L; adalimumab: 4.6 mg/L; 95% CI, 3.4-5.8 mg/L) compared with those who responded to treatment (etanercept: 2.5 mg/L; 95% CI, 2.0-3.0 mg/L; adalimumab: 6.4 mg/L; 95% CI, 5.0-7.8 mg/L).

This study was underpowered to demonstrate associations for each drug. Further limitations included the large proportion of patients missing antidrug antibody measurements and inclusion of secondary study end points that were not corrected for multiple tests.

The study authors concluded, “Findings of this study suggest that antidrug antibodies are associated with nonresponse to biologic drugs in RA and can be monitored in the

management of patients with RA, particularly nonresponders.”

Disclosure: One or more of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.