Influence of immunogenicity on the efficacy of long-term treatment with infliximab in rheumatoid arthritis

Abstract

The formation of anti-infliximab Abs during treatment with infliximab is associated with a loss of clinical response, the appearance of infusion reactions and discontinuation of treatment.

Cytokines as Therapeutic Targets in Rheumatoid Arthritis and Other Inflammatory Diseases

“…The reported prevalence of anti-infliximab antibodies varies greatly depending on the assay and timing, but appears to be around 30% in RA (PascualSalcedo et al, 2011) and may be as high as 61% in Crohn's disease (Baert et al, 2003), with this latter high prevalence most likely due to the episodic dosing schedule used in Crohn's. Although the development of anti-infliximab antibodies is associated with reduced efficacy of infliximab, these antibodies could also be detected in a significant proportion of patients who were classified as moderate or good infliximab responders (Pascual-Salcedo et al, 2011). This limits their utility in an individual patient, and measurement of anti-drug antibodies is therefore not currently part of standard clinical practice.…”

Comparison of immunogenicity test methods used in clinical studies of infliximab and its biosimilar (CT-P13)

“…The percentage of subjects who screened positive for ADAs in these comparative studies of CT-P13 and RMP was somewhat higher than some values previously reported in the literature [12,13,24,25,[27][28][29][30][31][32][33][34]37,38]. Most of the historical studies of RMP used the ELISA method to measure ADAs and rates were low in the majority of studies [27,28,31,32,37,38].…”

“…For example, one of the earliest studies to use ELISA to study the immunogenicity of infliximab, published in 1998, reported that 17.4% of patients receiving this drug in combination with methotrexate developed ADAs (TABLE 2) [28]. However, four studies reported rates similar to PLANETRA [27,29,33,34]. ADA rates were 40-50% in two studies that used the RIA method in patients with RA, which are similar results to those generated with ECL in PLANETRA [24,25].…”

“…Many published clinical studies have used the ELISA method to evaluate ADAs to infliximab in patient serum [19,[27][28][29][30][31][32][33][34][35]. In one Table 1.…”

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

“…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.…”