There were 109 eligible RCTs, involving 26,828 patients and 145 different treatments. Of these 82 reported incidence of relapse, 48 disease progression,29 MRI progression and 25 adverse events. Most trials were double-blind (at least 72%, depending on outcome), most described patient withdrawals (also at least 72%, depending on outcome), about half reported randomisation details and 49% used an intention-to-treat analysis.
Comparison with placebo
Eleven treatments were significantly better than placebo for patient relapse, levamisole was best (OR 6.00, 95% CI 1.54 to 23.40). Seven treatments reduced the incidence of disease progression, levamisole was best (OR 11.7, 95% CI 2.44 to 55.8). Seven treatments reduced the incidence of MRI progression, intravenous immunoglobulin (0.4g/kg) was best (OR 27.00, 95% CI 1.04 to 698.8). Only natalizumab (300mg) and fingolimod (0.5mg) were significantly better than placebo for all three outcomes. Six treatments increased adverse events, levamisole was worst (OR 80.6 95% CI 4.26 to 1523).
Comparison with interferon beta-1b (250μg)
Based on indirect analyses, sixteen treatments (or treatment combinations) were better than interferon beta-1b (250μg) for patient relapse, interferon beta-1a (44μg) with methylprednisolone (200mg/day) was best (OR 10.77 95% CI 6.38 to 19.4). Six treatments reduced the incidence of disease progression, levamisole was best (OR 5.05 95% CI 2.67 to 9.53). Only alemtuzumab (12 mg and 24mg) and levamisole were significantly better for both patient relapse and disease progression. No treatment was significantly better than interferon beta-1b for MRI progression.