Immunogenicity of interferon beta: differences among products

Abstract

Protein-based therapies are useful in a variety of diseases; however, their potential for immunogenicity is a disadvantage. Neutralizing antibodies (NAbs) that develop to interferon beta (IFNbeta) products (IFNbeta-1b, IFNbeta-1a-Avonex((R)), or IFNbeta-1a-Rebif((R))), which are first-line therapies for the treatment of multiple sclerosis, are reported to reduce the clinical efficacy of these agents. In individual clinical studies of each commercially available IFNbeta product, 28% to 47% of patients develop NAbs to IFNbeta-1b, 12% to 28 % to IFNbeta-1a-Rebif, and 2% to 6% to IFNbeta-1a-Avonex. Problems exist in comparing the incidence of NAbs among IFNbeta products across studies because of differences in study methodology, including assay methods, treatment duration, and the definition of NAb positive. Results from studies that have directly compared these products are consistent with results from the respective clinical trials of IFNbetas. Both the clinical trials and the independent studies have shown that NAbs develop more frequently with IFNbeta-1b treatment than with IFNbeta-1a treatment and that, among IFNbeta-1a products, NAbs develop more frequently with IFNbeta-1a-Rebif treatment than with IFNbeta-1a-Avonex treatment. Factors that may affect the immunogenicity of IFNbetas, including the dosing regimens and the biochemical properties of the products, are discussed.

Incidence, characterization, and clinical impact analysis of peginterferon beta1a immunogenicity in patients with multiple sclerosis in the ADVANCE trial

“…The incidence of NAbs emerging during treatment with nonpegylated IFN betas has been reported as ranging from 2% to 6% in trials of intramuscular IFN beta1a (Avonex, Biogen, Cambridge, MA, USA), from 12% to 28% with subcutaneous IFN beta1a (Rebif, Merck Serono, Geneva, Switzerland), and from 28% to 47% with subcutaneous IFN beta1b (Betaferon/Betaseron, Bayer-Schering, Leverkusen, Germany) [Bertolotto et al 2004]. Rates reported in clinical trials may vary due to differences in assay methods, timing of sampling and so on [Sorenson et al 2005;Ross et al 2000].…”

Strategies and Assays for the Assessment of Unwanted Immunogenicity

“…The issue is complex as the incidence of antibody formation varies greatly between proteins and also between products based on the same protein, in some cases, even with the same amino acid sequence (Antonelli et al, 1991;Wadhwa et al, 1999;Casadevall et al, 2002;Bertolotto et al, 2004). Antibody induction is also associated with variable clinical consequences depending on the product (Steis et al, 1988;Wadhwa et al, 1999;Casadevall et al, 2002).…”

Review of the clinical evidence for interferon β 1a (Rebif®) in the treatment of multiple sclerosis

“…) are needed to achieve an equivalent effect. These factors may account for the higher degree of immunogenicity and the likelihood of development of binding and neutralizing antibodies (NAbs) over the course of treatment (Bertolotto et al 2004). 28%-47% of patients develop NAbs to INF β 1b, 12%-28% to INF β 1a s.c. (Rebif ® ) and 2%-6% to INF β 1a i.m.…”

“…28%-47% of patients develop NAbs to INF β 1b, 12%-28% to INF β 1a s.c. (Rebif ® ) and 2%-6% to INF β 1a i.m. (Avonex ® ) (Bertolotto et al 2004), and their production has been associated with deterioration of therapeutic response (Malucchi et al 2004).…”