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BOSTON– Delivering subcutaneous glatiramer acetate as a 40-mg/mL dose three times weekly rather than 20 mg/mL daily halved the annualized rate of injection-related adverse events in a randomized, open-label, phase IIIb trial of patients with relapsing-remitting multiple sclerosis.
The reduction in the annualized rate of moderate and severe injection-related adverse events in those with lower-frequency dosing was even greater, at about 60%, in the trial, called GLACIER (Glatiramer Acetate Low Frequency Safety and Patient Experience), Dr. Jerry S. Wolinsky reported at the joint meeting of the European and Americas committees for Treatment and Research in Multiple Sclerosis.
Dr. Jerry S. Wolinsky
“As we all know, long-term, frequent injections are required for the first-line therapies for relapsing forms of multiple sclerosis, and this form of drug delivery presents a challenge for patients. Modification of the treatment regimen, such as using alternative dosages and lower-frequency administration schedules for these drugs with long-term proven efficacy, has the potential to improve the patient experience by reducing, perhaps, the number of adverse experiences that they have, improving tolerability, and in particular, potentially increasing adherence to treatments, especially in the longer-term,” Dr. Wolinsky said, explaining the basis for the GLACIER trial.
Glatiramer acetate 20 mg/mL administered by daily subcutaneous injection is a well-characterized treatment with a good long-term safety profile. It has been used for more than 20 years with more than 2 million patient-years of overall exposures, and it has established efficacy for the treatment of relapsing-remitting MS (RRMS). In January, the Food and Drug Administration approved a supplemental New Drug Application for the 40-mg/mL three times weekly regimen after it was shown to have an efficacy and safety profile similar to that of the 20-mg/mL regimen.
The GLACIER findings suggest that the glatiramer acetate 40-mg/mL three times per week dosing regimen is, for some patients, a favorable treatment option, particularly in those who want to be on glatiramer acetate, but who prefer fewer injections and more convenient dosing, concluded Dr. Wolinsky, director of the multiple sclerosis research group at the University of Texas Health Science Center at Houston.
The annualized rate of injection-related adverse events (IRAEs) in 108 adult patients with RRMS who were randomized to receive the thrice weekly injections was 35.3, compared with 70.4 in 101 patients who received daily injections (relative risk, 0.50). The annualized rate of moderate and severe IRAEs was 0.88 vs. 2.2 in the groups, respectively (relative risk, 0.40), he said.
The most common injection site reactions were pain, erythema, mass, swelling, and pruritus, and all of these were substantially reduced with lower-frequency dosing, compared with daily dosing. For example, the annualized rate of pain events was 24.8 vs. 55.3 with lower- vs. higher-frequency dosing, and the annualized rate of erythema events was 21.4 vs. 43.5.
GLACIER trial patients were aged 18 years or older (mean of 51 years) with a diagnosis of RRMS and an Expanded Disability Status Scale score of 0-5.5. Most (82%) were women, and 94% were white.
All were treated continuously with the 20-mg/mL daily dosing regimen for at least 6 months and were stable on that regimen for at least 2 months prior to screening for the GLACIER trial.
At least 75% treatment compliance was achieved by 99% of the GLACIER trial patients, and only 10 withdrew before completing the 4-month treatment phase, including 3 in the daily dosing group, and 7 in the lower-frequency dosing group. Only one patient withdrew because of an adverse event, Dr. Wolinsky said.
The GLACIER trial was funded by Teva Pharmaceutical Industries. Dr. Wolinsky disclosed ties to Teva and other companies marketing MS drugs.
