Concentrations of infliximab and anti-drug antibodies in relation to clinical response in patients with rheumatoid arthritis

Objective: The efficacy of anti-tumour necrosis factor- (anti-TNF-) treatment with infliximab (IFX) may be reduced by the development of anti-drug antibodies (ADAs). This study evaluated drug concentration and the presence of ADAs, relative to response, in rheumatoid arthritis (RA) patients treated with IFX.Method: Ninety-four RA patients were consecutively included and assessed for disease activity at baseline, and after 14, and 30 or 52weeks. Serum IFX concentration and ADAs were analysed using in-house enzyme-linked immunosorbent assays. ADA analysis was based on binding to TNF--coated plates, with the lower detection limit set at mean+2sd of controls.Results: At 14 and 52weeks, 74.5% of the patients had moderate to good response. Good responders had significantly higher IFX concentrations than moderate and poor responders at 52weeks (6.61.4 mu g/mL vs 3.6 +/- 1.3 mu g/mL and 2.6 +/- 1.6 mu g/mL, respectively). An IFX concentration 4.66 mu g/mL at 14weeks yielded a moderate to good response at 30/52weeks, with 91.3% specificity and 39.3% sensitivity. Eleven patients dropped out owing to lack of efficacy and eight owing to side effects; three with IFX concentration 0.5 mu g/mL were ADA positive. At an IFX concentration 0.5 mu g/mL, 43.8% and 30.1% at 14 and 52weeks, respectively, were ADA positive. None of the good responders had ADAs.Conclusion: One-quarter of patients had an IFX concentration 0.5 mu g/mL but only 11.7% had ADAs. High IFX concentration was related to a good response, suggesting that the lack of response could be due to a lack of IFX, rather than to the presence of ADAs.