SAN DIEGO – It seems okay to switch patients with relapsing-remitting multiple sclerosis to 40-mg glatiramer acetate injections three times a week if the usual 20-mg daily injections get to be too much, according to Dr. Omar Khan, interim chair of the neurology department at Wayne State University in Detroit.
"Our patients love what the molecule does" for them, but some want to quit if the daily shots cause too much lipoatrophy or too many injection-site reactions. "I tell them rather than going off it, go every other day. [That] alternative is okay," he said in an interview.
Dr. Omar Khan
The assertion is based in part on the randomized, blinded GALA (Glatiramer Acetate Low Frequency Administration Study), which Dr. Khan led and presented at the annual meeting of the American Academy of Neurology.
The trial randomized 943 relapsing-remitting multiple sclerosis patients to 40 mg of subcutaneous glatiramer acetate (Copaxone) three times weekly and 461 patients to matched placebo injections.
After a year, the placebo patients had an annualized relapse rate of 0.505, compared with a rate of 0.331 for the glatiramer acetate (GA) patients, a 34.4% reduction (P less than .0001). Similarly, the cumulative number of new or enlarging T2 lesions was 34.7% lower in the GA group, and the cumulative number of enhancing T1 lesions was 44.8% lower (P less than .0001 for both).
Although the trial did not pit 20 mg daily against 40 mg three times a week, Dr. Khan noted that the cumulative weekly dose is similar in both regimens, and that the response seen in the 40-mg group was comparable to what would be expected with 20 mg daily.
Injection-site redness, itching, and pain were more common in the GA group, as were headaches; 8.9% of the GA patients and 6.7% of the placebo patients left the study. Those results are also consistent with 20-mg daily injections.
There were no significant baseline differences between the groups. About 70% of the patients were women, they were about 38 years old on average, and almost all were white. The mean baseline Expanded Disability Status Scale score was about 2.7 in both arms, and patients were about 8 years out from diagnosis. The GA group had a baseline T2 lesion load of 19.7 mL, while the placebo group a baseline load of 17.4 mL.
It had been at least 2 years since any of the subjects had monoclonal antibodies, at least 6 months since they had used systemic corticosteroids, and at least 2 months since using immunomodulators. All the patients were GA naïve. The majority were from eastern Europe.
"We have a small phase II immunologic study," Dr. Khan noted, that pitted 20 mg daily against 40 mg every other day. "There were a lot of advantages of taking it every other day" – fewer injection-site reactions and the like – and "immunologically there was no difference" between the two regimens, he said. The study hasn’t been published yet.
In general, "if you look at just your general clinical observations, you can’t tell" which regimen patients are using, he said.
There’s debate about whether it’s better to start patients on a daily regimen, or if it’s okay to go with less frequent injections right out of the gate.
"You might generate a better Th2 [T-cell] shift if you keep them on every day for a few months, and then alter them. It could be true. The fact is that that sample in a large cohort does not exist. [Either way,] it doesn’t change a whole lot because at 6 months [and] 12 months everybody is doing well," Dr. Khan said.
In the meantime, "many of our patients routinely take [GA] less than every other day. They skip weekends; they create their own regimens," he said.
Teva Pharmaceuticals, the maker of GA, paid for the study. Dr. Khan has received personal compensation and research support from Teva, Biogen-Idec, and other companies.