SAN DIEGO—A drug formulation made of polyethylene glycol chains attached to interferon beta-1a (PEGylated interferon beta-1a) may reduce annualized relapse rate significantly for patients with relapsing-remitting multiple sclerosis (MS), researchers reported at the 65th Annual Meeting of the American Academy of Neurology. The drug may also prolong the time to first relapse and reduce the accumulation of disability.
In a phase III pivotal clinical trial, annualized relapse rate was 27.5% lower for patients with MS who received PEGylated interferon beta-1a once every four weeks, compared with patients who received placebo, said Peter Calabresi, MD, Professor of Neurology at the Johns Hopkins Multiple Sclerosis Center in Baltimore. Annualized relapse rate was 35.6% lower among patients receiving the drug every two weeks, compared with patients receiving placebo.
The hazard ratio of a prolonged time to first relapse was 0.61 for patients who received the drug every two weeks and 0.74 for patients who received the drug every four weeks. At one year, disability accumulation was significantly reduced among active patients, compared with controls. The hazard ratio for reduced disability accumulation was 0.62 for all treated patients.
Comparing Two Dosing Frequencies With Placebo
Dr. Calabresi and colleagues enrolled approximately 1,500 patients with relapsing-remitting MS in a two-year, multicenter, randomized, double-blind study. Eligible patients were younger than 65 and had an Expanded Disability Status Scale (EDSS) score of 5 or lower. The trial’s primary end point was annualized relapse rate at one year. Secondary end points included the proportions of patients who relapsed during one year, the proportions of patients with disability progression over one year, and new and newly enlarging T2 hyperintense lesions. The trial was conducted at sites located in India, North America, Western and Eastern Europe, and other countries.
Equal numbers of patients were randomized to receive placebo, 125 µg of PEGylated interferon beta-1a subcutaneously once every four weeks, or 125 µg of PEGylated interferon beta-1a subcutaneously once every two weeks. The treatment groups were well balanced in terms of age, gender, and race. Most patients had an EDSS score lower than 4, and MRI activity was well distributed.
PEGylated Interferon Beta-1a Reduced MRI Activity
At one year, patients receiving PEGylated interferon beta-1a every four weeks had a 28% reduction in new and newly enlarging T2 lesions, compared with controls. Patients receiving the drug every two weeks had a 67% reduction in T2 lesions, compared with controls.
Participants who received PEGylated interferon beta-1a every four weeks had a 36% reduction in gadolinium-enhancing lesions, compared with participants receiving placebo. This result was not statistically significant, but was “a strong trend,” said Dr. Calabresi. Participants who received PEGylated interferon beta-1a every two weeks had an 86% reduction in gadolinium-enhancing lesions, compared with controls, and this result was highly significant.
Researchers observed neutralizing antibodies in less than 1% of patients in both treatment arms. Adverse events were similar in both treatment groups, and the majority of adverse events were mild or moderate. Common adverse events included injection-site reactions, influenza-like illness, and pyrexia. Slightly more active patients than controls dropped out of the trial because of adverse events.
“At year one of the placebo-controlled component of the trial, which was [the time of our] preplanned primary analysis, PEGylated interferon had an effect on the clinical and radiologic measures and seemed to offer the safety profile of presently available interferon beta-1a molecules,” concluded Dr. Calabresi.
—Erik Greb
Senior Associate Editor
Suggested Reading
Hu X, Miller L, Richman S, et al. A novel PEGylated interferon beta-1a for multiple sclerosis: safety, pharmacology, and biology. J Clin Pharmacol. 2012;52(6):798-808.
Kieseier BC, Calabresi PA. PEGylation of interferon-b-1a: a promising strategy in multiple sclerosis. CNS Drugs. 2012;26(3):205-214.
Shirani A, Zhao Y, Karim ME, et al. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2012;308(3):247-256.