title: Recombinant and natural human interferons: analysis of the incidence and clinical impact of neutralizing antibodies.
abstract: This review summarizes and analyzes the clinical outcomes following treatment of a wide range of diseases with recombinant interferons (r-IFNs) and/or natural interferons (n-IFNs). The investigation focuses on the frequency of neutralizing antibodies (NABs) directed against IFN, which are formed during treatment and their clinical impact. r-IFNs (α-2a, α-2b, β-1a, and β-1b) induced seroconversion with generation of NABs in 17.2% of patients studied. The highest incidence of NABs occurred in macular degeneration (61.4%) with the lowest in multiple sclerosis (14.7%). The incidence of antibodies induced against n-IFNs was very low (<0.2%) and was significantly less than that seen for r-IFNs (P<0.0001). Overall, the fraction of relapsed and refractory patients is statistically greater in NAB positive patients compared to NAB negative patients (<0.0001), whereas the percentage of responding patients is higher in the NAB negative cohort (P<0.001). Finally, we also analyzed relapsed and refractory NAB positive patients who switched treatment to n-IFN, such as leukocyte derived Alferon N Injection® (α-n3) or Wellferon® (α-n1). Overall, in 33/40 (82%) of these relapsed or refractory patients, switching to n-IFNs restored the clinical response. This result is consistent with serology studies showing that the NABs directed against r-IFNs do not effectively cross-react with n-IFNs.
authors: Department of Clinical Research, Hemispherx Biopharma, Inc., Philadelphia, Pennsylvania 19103, USA. david.strayer@hemispherx.net
authors: David R
authors: DR
authors: Strayer
authors: William A
authors: WA
authors: Carter
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D003429:Cross Reactions; D006801:Humans; D015994:Incidence; D007370:Interferon Type I / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D057134:Antibodies, Neutralizing; D007370:Interferon Type I; D011994:Recombinant Proteins