Development of antiinfliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis

TLDR

Infliximab therapy can elicit anti‑infliximab IgG antibodies. The study evaluated the clinical significance of these antibodies in rheumatoid arthritis patients. In a cohort of 51 RA patients treated with infliximab, anti‑infliximab antibodies were measured by radioimmunoassay and serum drug levels by ELISA, and the results were correlated with EULAR response criteria over one year. Antibodies were present in 43% of patients and were associated with a lower response rate (36% versus 69% in antibody‑negative patients) and with infusion‑related allergic reactions, underscoring their clinical relevance.

Abstract

Abstract Objective Treatment of patients with infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor, may result in the formation of infliximab‐specific IgG antibodies. This study evaluated the clinical significance of these antibodies in patients with rheumatoid arthritis (RA). Methods Antiinfliximab antibodies were measured using a newly developed radioimmunoassay in a cohort of 51 consecutive patients with RA treated with infliximab, with a followup of 1 year. In addition, serum infliximab levels were determined by enzyme‐linked immunosorbent assay. The results were analyzed in relation to the clinical response to treatment according to the European League Against Rheumatism criteria. Results Antibodies against infliximab were detected in 22 patients (43%). Patients without detectable antiinfliximab antibodies (n = 29 [57%]) were significantly more often classified as responders (20 of 29 [69%]) compared with patients with detectable antiinfliximab antibodies (8 of 22 [36%]; P = 0.04). Three patients had an infusion‐related allergic reaction, all of whom had detectable antiinfliximab antibodies. Conclusion In this study, nearly half of the RA patients treated with infliximab developed antiinfliximab antibodies within the first year of treatment. This seems to be clinically relevant, since development of antiinfliximab antibodies is associated with a reduced response to treatment.