BOSTON—Delivering subcutaneous glatiramer acetate as a 40-mg/mL dose three times weekly, rather than 20 mg/mL daily, may reduce the annualized rate of injection-related adverse events by half, according to research presented at the 2014 Joint ACTRIMS–ECTRIMS Meeting. The results are from a randomized, open-label, phase III b trial of patients with relapsing-remitting multiple sclerosis (MS).
The reduction in the annualized rate of moderate and severe injection-related adverse events in patients who received lower-frequency dosing was about 60%, said Jerry S. Wolinsky, MD, Director of the MS Research Group at the University of Texas Health Science Center at Houston. The trial was called Glatiramer Acetate Low Frequency Safety and Patient Experience (GLACIER).
“As we all know, long-term, frequent injections are required for the first-line therapies for relapsing forms of MS, 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 he or she has, improving tolerability, and, in particular, potentially increasing adherence to treatments, especially in the longer-term,” said Dr. Wolinsky. The GLACIER trial was designed, in part, to test the regimen’s potential to yield these improvements.
Patients May Prefer Fewer Injections
Glatiramer acetate 20 mg/mL administered by daily subcutaneous injection is a well-characterized treatment with a good long-term safety profile. The drug has been used for more than 20 years, has accumulated more than two million patient-years of overall exposures, and has established efficacy for the treatment of relapsing-remitting MS. In January 2014, the FDA 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 daily 20-mg/mL regimen.
The GLACIER findings suggest that the 40-mg/mL dosing regimen of glatiramer acetate is a favorable treatment option for some patients, particularly people who want to be on glatiramer acetate, but who prefer to take fewer injections and have more convenient dosing, concluded Dr. Wolinsky.
The annualized rate of injection-related adverse events in 108 adult patients with relapsing-remitting MS 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 injection-related adverse events was 0.88 vs 2.2 in the groups, respectively (relative risk, 0.40), said Dr. Wolinsky.
The most common injection-site reactions were pain, erythema, mass, swelling, and pruritus, and all of these reactions were substantially reduced with lower-frequency dosing, compared with daily dosing. For example, the annualized rate of pain events was 24.8 with lower-frequency dosing vs 55.3 with higher-frequency dosing, and the annualized rate of erythema events was 21.4 vs 43.5.
Patients Had Experience With Glatiramer Acetate
Patients in the GLACIER trial were age 18 or older (mean age, 51) with a diagnosis of relapsing-remitting MS and an Expanded Disability Status Scale score between 0 and 5.5. Most participants (82%) were women, and 94% of patients were Caucasian.
All participants had been treated continuously with the 20-mg/mL daily dosing regimen for at least six months and were stable on that regimen for at least two 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 people withdrew before completing the four-month treatment phase, including three participants in the daily dosing group and seven patients in the lower-frequency dosing group. One patient withdrew because of an adverse event, said Dr. Wolinsky.