Results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS)
study found high levels of antidrug antibodies (ADAbs) in patients with rheumatoid arthritis (RA) who were treated with certolizumab. The researchers also found that higher CZP drug levels were associated with improved European League Against Rheumatism (EULAR) 12-month response.
Investigators of the BRAGGSS study sought to evaluate the association between various certolizumab drug levels, ADAbs, and treatment response in patients with RA. They also evaluated longitudinal factors associated with ADAbs and the various drug levels.
“This study demonstrates for the first time that certolizumab ADAbs were detectable in 37% of patients with RA over 12 months of treatment,” the authors concluded in their study, which was published in the Annals of Rheumatic Diseases. “Detectable ADAbs were associated with lower certolizumab drug concentrations, but not independently with treatment response.”
The study cohort included 115 patients with RA who were treated with certolizumab. The researchers collected serum samples at 3, 6, and 12 months and measured disease activity scores and the EULAR response. At the same time periods, they measured drug levels with enzyme-linked immunosorbent assay (ELISA) and measured ADAbs with radioimmunoassay.
High Yield Summary
- Certolizumab ADAbs, detected in 37% of patients in this cohort at 12 months, were associated with lower drug levels
- Certolizumab drug levels were associated with EULAR response at 12 months
The presence of ADAbs was significantly linked to lower drug levels over 12 months (β=-0.037; 95% confidence interval [CI]: -0.055 to 0.018; P<.0001), but it was not independently associated with EULAR response at 12 months (β=0.0013; 95% CI: -0.0032 to 0.00061; P=.18).
However, using ordinal regression, drug levels were associated with EULAR response at 12 months (β=0.032; 95% CI: 0.0011 to 0.063; P=.042).
“Certolizumab drug levels may be useful in therapeutic drug monitoring in combination with clinical parameter assessment,” the authors wrote. “Measurement of ADAbs may facilitate the interpretation of low drug levels and provide valuable information about future strategy. More information is required, however, on the cost-effectiveness of using these tests before implementation in clinical practice.”
Summary & Clinical Applicability
The authors note that this is the first study to find an association between detectable certolizumab ADAbs and drug concentrations, while other studies have demonstrated that high disease burden may be associated with ADAb formation in TNFi-treated patients.
Pretreatment swollen joint count was also significantly higher in patients with detectable ADAbs, which suggests that baseline inflammation may be associated with drug concentrations and certolizumab ADAbs.
“While several TNFi therapeutic drug-monitoring studies have used trough-level serum samples to measure both ADAbs and drug levels to reduce drug interference, ascertainment of random levels is clinically practical,” the authors wrote.
Limitations & Disclosures
The authors note that the 37% of patients with detectable ADAbs may under-represent the true value due to drug interference. The study also did not identify a clear drug concentration cut-off for treatment response in patients with non-trough samples.
Study author M.J. is a clinical training fellow funded by the Medical Research Council , ICON, GlaxoSmithKline, AstraZeneca, and the Medical Evaluation Unit.
Jani M, Isaacs JD, Morgan AW, et al. High frequency of antidrug antibodies and association of random drug levels with efficacy in certolizumab pegol-treated patients with rheumatoid arthritis: results from the BRAGGSS cohort. Ann Rheum Dis. 2016; doi:10.1136/annrheumdis-2015-208849.