DALLAS – Subcutaneous administration of pegylated interferon every 2 or 4 weeks to patients with relapsing-remitting multiple sclerosis was associated with low rates of immunogenicity in a phase III, double-blind randomized trial.
At year 2 of the ADVANCE trial, persistent treatment-emergent antibodies occurred in 1% of patients who’d received pegylated interferon (PEG-INF) beta-1a (at 125 mcg delivered subcutaneously either every 2 weeks or 4 weeks. Patients given 1 year of placebo, followed by 1 year of dose-frequency–blinded PEG-INF beta-1a, had a similarly low rate.
Dr. Scott Newsome
Modification of a drug by adding polyethylene glycol molecules (pegylation) increases its half-life. It may also reduce the drug’s immunogenicity.
"Pegylated interferon may provide efficacy and safety to what we see with currently available therapies, with the added advantage of lower dosing frequencies per month, which may improve compliance for injectable [therapies], and possibly decrease immunogenicity," said Dr. Scott Newsome, director of the neurology outpatient infusion center at Johns Hopkins Hospital, Baltimore.
The overall incidence of antipeginterferon antibodies during the 2 years of observation was 7% in the total study population of 1,516 patients, with no difference between treatment arms (3% in the placebo arm vs. less than 1% in those given PEG-INF beta-1a every 2 weeks and 2% in those given it every 4 weeks).
During the 2-year observation of the blinded dosage, the incidence of binding antibodies was 4% in the group that got PEG-INF beta-1a every 2 weeks and 2% with PEG-INF beta-1a every 4 weeks. Antipeginterferon titers were 2% and 6%, respectively.
"I’d also like to point out that the incidence rate of interferon beta-1a neutralizing antibodies was exceedingly low, less than 1% across the entire study and across both treatment arms," Dr. Newsome said at a meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
"No discernible impact on safety or tolerability was observed in this study," Dr. Newsome said, adding that the rate of adverse events such as injection-site reactions did not differ by antibody status or titer.
The findings strengthen PEG-INF’s profile as another potential interferon treatment for relapsing-remitting multiple sclerosis. In March of this year, the Food and Drug Administration extended its review of the Biogen IDEC product by 3 months; their decision is still forthcoming. If approved, the manufacturer plans to market the drug as Plegridy.
The results of the ADVANCE trial presented earlier this year at the annual meeting of the American Academy of Neurology, indicated that the drug met all primary and secondary efficacy endpoints by the end of year 1, and continued to show a similar efficacy and safety profile in year 2.
Dr. Newsome declared he has received funding from Biogen IDEC and Genzyme. Biogen IDEC sponsored this study.
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