Randomized, prospective, rater-blinded, four-year, pilot study to compare the effect of daily versus every-other-day glatiramer acetate 20 mg subcutaneous injections in relapsing-remitting multiple sclerosis

BACKGROUND: The recommended dose of GA in RRMS is 20 mg subcu-taneous (SC) daily (QD) although the optimal dose remains unknown.There is considerable interest in alternate dosing regimens of GA inRRMS. Daily SC injectable therapy can be challenging for long-termpatient compliance. OBJECTIVE: We conducted a pilot trial to comparethe effect of GA 20 mg SC daily versus every other day (QOD) inRRMS. The primary endpoint was based on a composite of clinical,MRI, and immunologic outcomes. METHODS: Treatment naïve RRMSpatients were randomized to GA 20 mg SC QD or QOD and followedprospectively for 2 years. After 2 years, patients in each group weregiven the option to continue or switch to the other group, and fol-lowed for an additional 2 years. EDSS was recorded every 6 months bya rater blinded to dosing allocation. Brain MRI scans were obtained atbaseline, and years 2 and 4. Blood for immunologic testing wasobtained at baseline and multiple time points after randomization. RESULTS: 30 patients were randomized to GA 20 mg SC given QD orQOD. Both groups were well-matched for age, disease duration, EDSS,relapse rate, T2W and gadolinium (Gd) enhancing lesions. After2 years, there were no differences in the relapse rate, disease progres-sion, Change in T2W lesion volume, or Gd enhancing lesionsbetween the two groups. In vitro proliferation of GA-responsive T-cellsand Th1/Th2 cytokine expression did not differ between the twogroups at any time point after randomization. After 2 years, allpatients in the QD group opted to switch to QOD. After a total of4 years of prospective follow-up, there was no difference between theQD-QOD cross over group and the always QOD group. Additionaldata on imaging and immunologic outcomes will be presented. CONCLUSIONS: This pilot study suggests that GA 20 mg SC adminis-tered QD or QOD may be equally effective in RRMS. This may haveimplications for the long-term use of GA. However, large multi-centerstudies are warranted to confirm our findings and to identify the opti-mal dose of GA in RRMS.