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

Abstract

An open-label extension study of the phase III trial of intramuscular interferon beta-1a (IFNbeta-1a-Avonex) was conducted to evaluate the immunogenicity and safety of IFNbeta-1a-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 IFNbeta-1a-Avonex 30 microg intramuscularly once weekly for six years, for a treatment duration of up to eight years in patients who received IFNbeta-1a-Avonex in the phase III trial. Serum levels of IFNbeta 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, 218 had participated in the phase III study (103 placebo, 115 IFNbeta-1a-Avonex) and 164 had not participated; 24 of the 164 were IFNbeta-naïve. At baseline, 281 patients were negative for IFNbeta antibodies (NAb-). NAbs (titre> or = 20) developed at any time over six years in 5% of these patients. Of 140 patients who had been on IFNbeta-1b-Betaseron, 49 were positive for NAbs (NAb+) at baseline; 11 of 115 who had been on IFNbeta-1a-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 IFNbeta-1a-Avonex, with a median time of approximately six months. Ten patients who had been on Betaseron had NAb titres > or = 100; five remained NAb+ during six years on IFNbeta-1a-Avonex and five seroconverted to NAb-, but only after at least two years. Five patients who had been on IFNbeta-1a-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 IFNbeta-1a-Avonex had NAb titres > or = 100; five of these remained NAb+ at six years. No patient with a NAb titre > 1000 seroconverted to NAb-, whether initially treated with IFNbeta-1a-Avonex or -Betaseron. Adverse events were similar to those observed in the pivotal phase III trial. Results from this trial indicated that IFNbeta-1a-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 IFNbeta product.

Neutralizing antibodies to interferon beta: Assessment of their clinical and radiographic impact: An evidence report: [RETIRED]

“…50 Also, the reversion rate from NAb-positive to NAb-negative status was 50% in a small Italian study after 3 to 4 years 41 and it was 54% after 3 years in the North American trial of IFN␤-1b in SPMS. 33 It seems that, despite continued treatment with IFN␤, the majority of NAb-positive patients will ultimately revert to NAb-negative status after 3 to 8 years of therapy.…”

Evidence for Long-Term Use of Intramuscular Interferon Beta-1a: An Overview of Relapse, Disability, and MRI Data from Selected Clinical Trials

“…72 Of the 107 (28%) patients who discontinued, 38 (10%) voluntarily withdrew from treatment; 20 (5%) withdrew due to perceived worsening of MS; and 8 (2%) withdrew due to AEs. The incidence and types of AEs during the extension study were similar to those observed in the MSCRG study.…”

“…The incidence and types of AEs during the extension study were similar to those observed in the MSCRG study. 8,72 The most frequently reported AEs were flu-like symptoms (74%), headache (58%), muscle aches (48%), cold symptoms (46%), and accidental injury (48%). 72 A total of 120 patients (31%) experienced a serious AE, which included 36 (9%) patients with a relapse and 12 (3%) with accidental injury.…”

“…8,72 The most frequently reported AEs were flu-like symptoms (74%), headache (58%), muscle aches (48%), cold symptoms (46%), and accidental injury (48%). 72 A total of 120 patients (31%) experienced a serious AE, which included 36 (9%) patients with a relapse and 12 (3%) with accidental injury. Nine (2%) patients discontinued treatment due to AEs, and the most common of these types of events were flu-like symptoms (n = 3), asthenia (n = 2), fever (n = 2), and relapse (n = 2).…”

“…Despite of IM IFNβ-1a when administered to patients for over 6 years. 72 The extension period was not restricted to patients who had participated in the main MSCRG study but was also open to new patients. All patients received once weekly IM IFNβ-1a 30 µg for 6 years (new patients) or up to 8 years (MSCRG patients).…”