Benefit-risk analysis of glatiramer acetate for relapsing-remitting and clinically isolated syndrome multiple sclerosis.

BACKGROUND Glatiramer acetate (GA) and interferon beta-1 are licensed for treating patients with multiple sclerosis (MS). However, they have slightly different indications, side effect profiles, and tolerability. OBJECTIVE The purpose of this study was to assess the benefit-risk (BR) profile of GA in relapse-remitting MS (RRMS) and clinical isolated syndrome (CIS). METHODS MEDLINE, EMBASE, and the Cochrane Register were searched for randomized controlled trials and comparative observational cohort studies in patients older than 18 years who were treated with 20 mg daily of subcutaneous GA for RRMS or CIS. Uncommon risks of GA were assessed in the World Health Organization (WHO) global spontaneous adverse reaction (AR) reports database (Vigibase). RESULTS A total of 248 potentially relevant articles were identified by the search; of these, 11 studies were included in the review: 7 trials and 4 cohort studies with a total of 4759 patients. The proportion of studies included from the search was 4.4% of all titles, 9.3% of all reviewed abstracts, and 45.8% of all eligible articles for review. In patients with RRMS relapse-free rates were higher with GA than with placebo (relative risk [RR] = 1.35; 95% CI, 0.99-1.84) and similar to interferons (IFNs) (RR = 0.99; 95% CI, 0.93-1.06). There was a 33% reduction in clinical progression (RR = 0.69; 95% CI, 0.42-1.13) for GA compared with placebo and an 18% reduction (RR = 0.82; 95% CI, 0.68-0.98) compared with IFNs. Study discontinuations because of adverse events were similar for GA and IFNs (RR = 0.89; 95% CI, 0.57-1.41). In Vigibase, 1271 cases were identified with a suspected relation to GA. Several ARs were identified as statistically strong signals of disproportionate reporting for GA compared with IFNs. WHO critical ARs combined were similar between GA and IFNs, with a reporting rate of 69 per 100,000 person-years for GA. The relative net BR difference was 10.2% in favor of GA compared with placebo and 6.4% compared with IFNs. CONCLUSIONS GA reduced relapses and clinical progression compared with placebo or standard treatment and clinical progression compared with IFNs. Serious adverse events were comparable in GA and IFNs. The BR assessments that were based on these data found that the clinical benefits of GA outweigh the risks, although results differ, depending on the quantitative BR model used, and are limited by the absence of reliable data for assigning weights to the model.

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