Eight-year immunogenicity and safety of interferon beta-1a-Avonex® treatment in patients with multiple sclerosis

An open-label extension study of the phase III trial of intramuscular interferon beta-la (IFN beta-la-Avonex) was conducted to evaluate the immunagenicity and safety of IFN beta-la-Avonex over six years in patients with relapsing multiple sclerosis (MS). Patients who participated in the pivotal phase III study were offered enrolment, entry was also open to patients who had not participated. All patients received IFN beta-la-Avonex 30 mu g intramuscularly once weekly for six years, for a treatment duration of up to eight years in patients who received IFN beta-la-Avonex in the phase III trial. Serum levels of IFN beta antibodies were measured every six months using a screening enzyme-linked immunosorbent assay (ELISA) followed by an antiviral cytopathic effect assay to detect neutralizing antibodies (NAbs) in serum samples positive on ELISA. The incidence of adverse events and laboratory test results assessed safety. Of 382 total patients, 2 18 had participated in the phase III study (103 placebo, 115 IFN beta-la-Avonex) and 164 had not participated, 24 of the 164 were IFN beta-naive. At baseline, 281 patients were negative for IFN beta antibodies (NAb -). NAbs (titre >= 20) developed at any time over six years in 5% of these patients. Of 140 patients who had been on IFN beta-lb-Betaseron, 49 were positive for NAbs (NAb +) at baseline; 11 of 115 who had been on IFN beta-la-Avonex were NAb+ at baseline. Thirty-nine of 49 patients who had been on Betaseron and were NAb + had titres < 100, 36 of these 39 seroconverted to NAb - while on IFN beta-la-Avonex, with a median time of approximately six months. Ten patients who had been on Betaseron had NAb titres >= 100; five remained NAb + during six years on IFN beta-la-Avonex and five seroconverted to NAb -, but only after at least two years. Five patients who had been on IFN beta-la-Avonex during the clinical trial were NAb + with titres <100 at baseline; four seroconverted to NAb -, with a median time of two to three years. Six patients who had been on IFN beta-la-Avonex had NAb titres >= 100, five of these remained NAb + at six years. No patient with a NAb titre > 1000 seroconverted to NAb -, whether initially treated with IFN beta-Ia-Avonex or -Betaseron. Adverse events were similar to those observed in the pivotal phase III trial. Results from this trial indicated that IFN beta-la-Avonex was associated with a low incidence of NAbs and was well tolerated for up to eight years. Further the results indicate that persistence of NAbs is dependent on titre and IFN beta product.