Four trials (n=1,407 patients) were included in the review. Study sample size ranged from 72 to 942 patients. The quality of the included trials was generally high: three trials scored at least 4 out of 5 and one trial scored 3 out of 5. Funnel plot analysis revealed a degree of asymmetry, which indicated potential for publication bias.
Effectiveness: Compared with placebo, natalizumab at a dose of 3mg/kg or 6mg/kg or 300mg every four weeks had a statistically significantly lower risk of at least one relapse (RR 0.50, 95% CI 0.42 to 0.61; two trials); there was no evidence of statistical heterogeneity for this analysis. When all doses of natalizumab were compared with placebo, there was no statistically significant difference in the risk of at least one relapse (RR 0.70, 95% CI 0.42 to 1.17; four trials). There was no statistically significant difference between natalizumab compared with placebo in terms of at least one new Gd-enhancing lesion (RR 0.22, 95% CI 0.05 to 1.01; two trials). There was evidence of statistical heterogeneity for both of these analysis (Q test p<0.01).
Tolerability: Compared with placebo, natalizumab had a statistically significantly higher risk of serious adverse events (RR 0.39, 95% CI 0.29 to 0.52; two trials). There was no statistically significant difference between natalizumab and placebo in terms of any adverse events (RR 0.99, 95% CI 0.96 to 1.01; four trials) and withdrawal due to adverse events (RR 1.43, 95% CI 0.68 to 3.02; two trials). There was no evidence of statistical heterogeneity in any of the tolerability analyses.