Adding oral albuterol to glatiramer injections appears to enhance the clinical response of multiple sclerosis patients during the first year of therapy, according to a report in the September issue of the Archives of Neurology.
The combined treatment was superior to glatiramer plus placebo at 6 months and 12 months, but that benefit was no longer evident at 24 months, said Dr. Samia J. Khoury of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her associates.
Albuterol is a beta-2 adrenergic agonist, and adrenergic mechanisms play a major role in modulating the immune response. Oral albuterol has been reported to decrease interleukin 12 and gamma-interferon levels in MS patients.
Dr. Khoury and her colleagues assessed albuterol as an add-on therapy in 44 patients with relapsing-remitting MS who were just beginning glatiramer treatment. The study subjects had never used immunomodulatory or immunosuppressive agents.
Twenty-three patients were randomly assigned to receive glatiramer injections plus oral albuterol and 21 to receive glatiramer injections plus oral placebo. All were followed at 6-month intervals for 2 years. Only 27 (61%) completed the full study period; however, 9 subjects in the combined-therapy group and 8 in the single-therapy group dropped out. A total of 39 subjects contributed to the analysis, and the mean duration of “time on study” was approximately 80 weeks for both groups.
The primary clinical end point was improvement on the Multiple Sclerosis Functional Composite (MSFC) score at 6, 12, 18, and 24 months.
Study subjects taking the combined therapy, compared with those taking glatiramer plus placebo, had significantly higher scores at 6 months (mean difference between groups 0.26) and 12 months (mean difference 0.21). Most of this difference was attributed to performance on a single measure, a timed 25-foot walk. These scores improved in subjects who took glatiramer plus albuterol but worsened in those taking glatiramer plus placebo.
It is unlikely that this difference would have resulted from albuterol’s known capacity to improve pulmonary function, the investigators noted (Arch. Neurol. 2010;67:1055-61).
The apparent benefit from add-on albuterol was accompanied by a decrease in interleukin-13 levels.
Albuterol’s additive benefit was no longer evident at 24 months (mean difference 0.09), as there was no significant difference between the two treatment groups on MSFC scores at that time.
Changes in scores on the Expanded Disability Status Scale and on an ambulation index were not significantly different between the two study groups at any assessment time.
More subjects taking glatiramer plus placebo (eight patients) than taking glatiramer plus albuterol (two patients) experienced relapses during the study. Moreover, the time to first relapse was longer in subjects taking the combined therapy. The annualized relapse rate was 0.09 relapses per year for combined therapy and 0.37 for glatiramer plus placebo.
Both study groups showed decreases in the number of brain lesions on MR imaging with treatment, and there were no significant differences between the two groups. Over time, subjects receiving combined therapy showed a smaller decrease in brain parenchymal fraction, but this study was not powered to detect a significant difference in this outcome.
“Many subjects experienced adverse events, but most were mild. One subject in each treatment group had a serious adverse event,” Dr. Khoury and her associates said.
Of the moderate or severe adverse events, only three were considered to be related to treatment: one reaction at the glatiramer injection site, one episode of leg weakness, and one episode of chest tightness.
“We conclude that treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis,” they wrote.
This study was supported in part by an Autoimmunity Center of Excellence study grant from the National Institute of Allergy and Infectious Diseases. Dr. Khoury and her associates reported ties to EpiVax, LifeCycle Pharmaceutical, PDL, BioPharma, Repligen, Wyeth, Allozyne, EISAI Research Institute, Xceed Molecular Corporation, Actelion, AutoImmune, Biogen Idec, EMD Serono, Enzo, Genentech, Teva Neuroscience, Vascular Biogenics, Millenium Pharmaceuticals, Bayer, and Pfizer.