Rheumatology (Oxford) 2016 Nov 25;55(11):2050-2055. Epub 2016 Aug 25.
NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
Objective: To determine the concordance between RIA and bridging ELISA at detecting anti-drug antibodies (ADAbs) in the context of random adalimumab levels and investigate the additional clinical utility of detecting ADAbs in RA patients who test ADAb positive by RIA and negative by ELISA.
Methods: ADAb levels were determined using RIA and bridging ELISA in 63 adalimumab-treated RA patients (159 samples). Immunogenicity concordance was determined using receiver operating characteristic curves. To determine the additional clinical value provided by a positive RIA in the presence of negative ELISA, association between treatment response (ΔDAS28), adalimumab drug levels and ADAbs was evaluated longitudinally using generalized estimating equation.
Results: Of the 60 RIA samples (n = 31 patients), 19 (n = 10 patients) were also ELISA, corresponding to 31.7% of samples. Area under the curve for detecting ADAbs using ELISA (compared with RIA) using receiver operating characteristic curves was 0.65 (95% CI: 0.59, 0.71); this increased to 0.91 (95% CI: 0.81, 0.99) if ADAbs were ⩾100 AU/ml using RIA. In RIA/ELISA patients, adalimumab levels were associated with ΔDAS28 over 12 months [regression coefficient: 0.098 (95% CI: 0.043, 0.15), P < 0.0001] and while ADAbs were significantly associated with drug level, they were not directly associated with ΔDAS28 over 12 months [β coefficient: 0.00083 (95% CI: -0.0038 to 0.0054), P = 0.72].
Conclusion: ADAbs were detected using ELISA more frequently when present in high titres as measured by RIA. In RIA/ELISA patients, only drug levels were significantly associated with treatment response. Although ADAbs were not independently associated with treatment response, they may be helpful in determining the aetiology of low drug levels.