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

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. 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. Results. Antibodies against infliximab were detected in 22 patients (43%). Patients without detectable antiinfliximab antibodies (n ‫؍‬

Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

“…It has been shown that patients with good response to TNFi therapy have higher drug trough serum levels than those with a poor response (28)(29)(30)(31). In accordance with the strong correlation between calprotectin and disease activity observed previously, our results show a significant inverse correlation between IFX and ETN and calprotectin, although no significant association was observed with ADA.…”

“…Only calprotectin distinguished between RA patients in clinical remission and those with low disease activity according to all indices analyzed, a finding that was also observed in PsA. Calprotectin serum levels correlated inversely with TNFi trough serum levels, which are known to be associated with a good therapeutic response (28)(29)(30)(31).…”

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

“…An unwanted consequence of BP therapy is the development of immunogenic responses, which in some cases have little or no impact but in other cases affect safety significantly, with induction of infusion reactions, hypersensitivity reactions and autoimmune syndromes occurring due to cross‐reactivity of anti‐drug antibody (ADA) with endogenous counterparts of the BP 3, 4, 5, 6, and/or decreased efficacy related to neutralization of the BP's biological activity or increasing its clearance 7, 8, 9. For these reasons, immunogenic potential of a BP is determined during clinical trials by measurement and characterization of ADA that develop during treatment; in some cases, monitoring for biopharmaceutical and ADA levels may be conducted during routine use of approved BPs to guide patient care 10, 11, 12.…”

Functional Analysis of the Anti-adalimumab Response Using Patient-derived Monoclonal Antibodies

“…Replacement (R) and silent (S) mutation frequencies were calculated for framework regions and CDRs based on the average number of nucleotides in all analyzed sequences according to the definitions of IMGT/Joinsolver (13). 2 and Fab fragments were generated using pepsin, and subsequent reduction and alkylation with dithioerythritol and N-ethylmaleimide, respectively, were as described previously (14).…”

“…2 However, some of the patients develop an immune response against the therapeutic, which results in the formation of anti-drug antibodies (ADA). The formation of ADA has been linked to lower serum drug levels and reduced clinical response (1)(2)(3)(4)(5)(6)(7). ADA formation can influence treatment efficiency via two possible mechanisms.…”