Glatiramer Acetate and Interferon Beta 1a and 1b for Clinically Isolated Syndrome: A Review of Clinical Effectiveness and Guidelines

Key Message

Sparse evidence was found in the published literature. One systematic review and one randomized controlled trial provided evidence on the clinical effectiveness of glatiramer, interferon beta-1a, and interferon beta-1b in people with clinically isolated syndrome. One set of evidence-based guidelines provided relevant recommendations. The evidence on each treatment regimen was derived from no more than two RCTs, suggesting a lack of diversity in the patient populations, and limiting opportunities for meaningful meta-analyses. Three of the five RCTs that were included in the systematic review reported on interferon beta-1a; in two trials the drug was delivered intramuscularly and in one, subcutaneously and at two dosages. One of the remaining RCTs reported on patients treated with glatiramer acetate while the other reported on patients treated with interferon beta-1b. Manufacturers of the interventions of interest sponsored the included studies and as such may have had opportunities to influence the selection of patients, comparators, and outcomes. Incidentally, there was some evidence of patient selection bias and discrepancy in the reporting of results between the systematic review and the randomized controlled trial. For these and other reasons, considerable caution must be taken in making inferences from the results presented in this report. Treatment effect was assessed with measurements of time to multiple sclerosis conversion, relative number of new brain lesions that developed during the study period, the change in volume of lesions that existed at study baseline, and the incidence of discontinuation due to adverse events. Overall, relative to placebo, specific doses of glatiramer acetate and beta-interferons slowed down the conversion from clinically isolated syndrome to clinically definite multiple sclerosis or McDonald multiple sclerosis and reduced the development of new brain lesions. Safety outcomes favoured glatiramer acetate and beta-interferons over placebo. The authors did not report on the statistical significance of these effects, nor was there direct comparison of active therapies.Based on a limited quantity of evidence from four randomized controlled trials, a guideline development group provided recommendations on discussing the benefits and risks of disease-modifying therapies, prescribing, monitoring patients with CIS, and stopping therapies.There was no identified evidence on incidence of progression to clinically definite multiple sclerosis, mortality, hospitalizations, quality of life, disability, time to disability, long-term disability progression, or relapse. None of the studies directly compared glatiramer acetate and beta-interferons. Recommendations on switching between therapies that were specific to patients with CIS were not found.