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New Dose of Glatiramer Acetate May Have Advantages, Compared With Standard Dose


 

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PHILADELPHIA—Among patients with relapsing-remitting multiple sclerosis (MS), a thrice-weekly 40-mg subcutaneous dose of glatiramer acetate, which the FDA approved in January 2014, reduces the rate of injection-related adverse events by approximately 50%, compared with the standard dose of 20 mg/day, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The 40-mg dose is associated with a similar reduction in the rate of direct injection-site reactions.

In a separate study, early treatment with 40 mg of glatiramer acetate was associated with a 31% reduction in the number of confirmed relapses, compared with delayed treatment. Early treatment also was associated with a 67.5% likelihood of relapse freedom, compared with delayed treatment. Early treatment did not affect the rate of disease progression significantly, compared with delayed treatment, but the open-label extension study was not designed to assess disease progression.

The 40-mg dose of glatiramer acetate could affect patient compliance in several ways. For example, patients may prefer receiving injections three times per week to receiving daily injections, but the latter schedule may be easier for patients to remember than the former. “I counsel my patients who want less-frequent injections to set their calendars up [and] to be careful about what they’re doing, because it will take a little bit more behavior change or adaptation on their part to do this correctly,” said Jerry Wolinsky, MD, Interim Chair of the Department of Neurology at the University of Texas in Houston.

Jerry Wolinsky, MD

One problem with the long-term injection of glatiramer acetate is that patients may develop lipoatrophy. “We expect, but don’t know, that with fewer injections, what has been a major compliance problem for some patients in the long run may be put off for years by this kind of a preparation,” added Dr. Wolinsky.

Safety Study Compared 20-mg and 40-mg Doses
Dr. Wolinsky and colleagues performed an open-label, multicenter study to compare the acceptability and tolerability of two formulations of glatiramer acetate. For the study, the researchers enrolled 209 patients with relapsing-remitting MS who had been receiving daily 20-mg injections of glatiramer acetate for at least six months. Eligible participants were 18 or older, were fully ambulatory, had an Expanded Disability Status Scale (EDSS) score between 0 and 5.5, and were relapse-free in the 60 days before randomization.

The investigators randomized 101 participants to continue daily 20-mg injections of glatiramer acetate. The remaining 108 patients were randomized to 40-mg injections of glatiramer acetate three times per week. At the end of a four-month study period, patients were given the option of continuing on 40-mg injections until the trial was completed. Dr. Wolinsky and colleagues conducted various assessments, including subject-reported outcome questionnaires and standard examinations and testing.

The study population differed from that of the typical clinical trial in MS, said Dr. Wolinsky. Average age for patients in this trial was more than 50, and the population included a larger proportion of women than is common in similar studies. In addition, patients’ average disease duration was approximately 16 years, and average time to diagnosis ranged from 10 to 12 years. Participants had a low reported exacerbation rate and a low EDSS score at study entry.

Patients Found the 40-mg Dose Convenient
The trial’s primary end point was the rate of injection-related adverse events, and 40-mg injections of glatiramer acetate were associated with a significant reduction in these events. Secondary end points included the treatment’s effect on questionnaires of physical and psychological well-being (as measured by the MS Impact Scale 29) and subjects’ perceptions of convenience and satisfaction. The researchers found no significant differences between treatment arms in the physical or psychological scores of the MS Impact Scale 29. Convenience scores on the Treatment Satisfaction Questionnaire for Medication-9 appeared to favor the high dose of glatiramer acetate.

Most adverse events in the trial were related to the direct injection, and no new safety signals were reported for glatiramer acetate. “The 40-mg three-times-a-week dosing regime appears to be a favorable treatment option for patients who want glatiramer acetate treatment but prefer fewer subcutaneous injections,” concluded Dr. Wolinsky.

Researchers Examined Efficacy of 40-mg Injections
Omar Khan, MD, Chair and Professor of Neurology at Wayne State University School of Medicine in Detroit, and colleagues conducted an open-label extension study to assess the ongoing safety and efficacy of thrice-weekly subcutaneous 40-mg injections of glatiramer acetate. Of the approximately 1,400 participants in a previous placebo-controlled study, 1,253 patients with relapsing-remitting MS agreed to participate in the open-label extension. The investigators grouped patients into two distinct arms. Participants in the early-start arm had received 40-mg injections of glatiramer acetate thrice weekly for 12 months in the placebo-controlled trial, and they continued to receive this treatment in the extension. Patients in the delayed-start arm had received placebo for 12 months in the placebo-controlled study and received thrice-weekly 40-mg injections of glatiramer acetate in the extension. The clinical end point was the total number of confirmed relapses.

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