title: Incidence and clinical significance of neutralizing antibodies in patients receiving recombinant interferon alfa-2a by intramuscular injection.
abstract: More than 1600 patients with neoplastic disorders have received recombinant human interferon alfa-2a (Roferon-A, Hoffmann-La Roche, Nutley, NJ) as part of ongoing or completed clinical trials. In this report, the efficacy of interferon alfa-2a therapy was compared with the incidence of antibodies to this interferon in 617 patients who received the drug by intramuscular administration. Antibody measurements were performed using a highly sensitive enzyme immunoassay, and an interferon antiviral neutralization bioassay. Partial or complete remission occurred in 28% (43 of 152) of the antibody-positive patients, and in 24% (112 of 465) of the antibody-negative patients (P = 0.33). The highest incidence of antibody formation occurred among patients with renal cell carcinoma and acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (44% and 34%, respectively). Both the duration of treatment and length of survival were significantly longer for antibody-positive than for antibody-negative patients. No significant intergroup differences emerged for response rates or for time to onset or duration of therapeutic response. When results from the above assays were compared to those used for the detection of antibodies to recombinant interferon alfa-2b (Intron A, Schering-Plough Inc., Kenilworth, NJ), the immunoradiometric assay method was determined to be seriously deficient for determination of antibody incidence. This decreased assay sensitivity may account for the reportedly lower incidence of antibodies to recombinant alfa-2b interferon.
authors.affiliation: Hoffmann-La Roche Inc., Nutley, New Jersey 07110, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Itri
authors.forename: M
authors.initials: M
authors.lastname: Campion
authors.forename: R A
authors.initials: RA
authors.lastname: Dennin
authors.forename: A V
authors.initials: AV
authors.lastname: Palleroni
authors.forename: J U
authors.initials: JU
authors.lastname: Gutterman
authors.forename: J E
authors.initials: JE
authors.lastname: Groopman
authors.forename: P W
authors.initials: PW
authors.lastname: Trown
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000276:immunology; D000906:Antibodies / Q000276:immunology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D015994:Incidence; D007273:Injections, Intramuscular; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000276:immunology*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000276:immunology; D009500:Neutralization Tests; D016719:Radioimmunodetection; D011994:Recombinant Proteins; D012074:Remission Induction; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000276:immunology; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins