Nine randomised controlled trials (RCTs) were included in the review (n=3,980 patients). Sample sizes ranged from 50 to 939. All the RCTs were double-blind and had Jadad scores of 3 or higher.
Number of multiple sclerosis patients with at least one relapse: The pooled relative risk showed a statistically significant benefit with interferon-beta treatment (RR 0.86, 95% CI 0.76 to 0.97; seven RCTs), but there was statistically significant heterogeneity (p = 0.006). In three RCTs using interferon-beta-1a, there was no benefit compared with placebo (but substantial heterogeneity). Three RCTs of interferon-beta-1b showed a statistically significant benefit with a fixed-effect model (RR 0.92, 95% CI 0.85 to 1.00; no significant heterogeneity), but not with a random-effects model. In patients with secondary progressive multiple sclerosis, there was no statistically significant benefit of treatment either overall or with interferon-beta-1b (three RCT; significant heterogeneity, p<0.001); this was also the case in patients with relapsing remitting multiple sclerosis (two RCTs; significant heterogeneity, p=0.004).
Mean change in Expanded Disability Status Scale (EDSS) score: There was no statistically significant benefit of treatment for either the 22μg or the 44μg dose of interferon-beta (two RCTs; significant heterogeneity, p<0.001).
Tolerability: There was a statistically significantly higher rate of discontinuations due to adverse events in the interferon-beta groups (RR 2.76, 95% CI 1.97 to 3.89) with no significant heterogeneity. There were no statistically significant differences between groups in deaths or completed or attempted suicides or depression (three RCTs). There were statistically significantly higher rates of flu like symptoms (six RCTs), injection-site reactions (five RCTs), injection-site inflammation (four RCTs), myalgia (five RCTs), leucopenia (three RCTs), lymphopenia (four RCTs) and increased alanine aminotransferase (three RCTs). The analyses did not show significant heterogeneity, except for injection site reactions and depression.