Long-term impact of interferon or Glatiramer acetate in multiple sclerosis: A systematic review and meta-analysis

In recent years the impact of disease-modifying drugs on long-term progression in multiple sclerosis (MS) was assessed both in observational studies and in extension of randomized controlled trial (RCT). Aim of this work was to quantitatively summarize by a meta-analysis the long-term impact of immunomodulatory drugs (Interferon-Beta (IFN-β) or Glatiramer Acetate (GA)) in relapsing-remitting (RR) MS patients. Methods We collected all published observational studies reporting the long-term efficacy of IFN-β or GA in RRMS patients. The primary outcome was the treatment effect on progression to a sustained EDSS score of 6 or to the Secondary Progressive (SP) phase. A non-parametric approach was adopted to test the overall treatment effect significance, while a random effect model was used to obtain a pooled quantitative estimate of the treatment benefit, in terms of hazard-ratios (HR) or Relative Risks, with their 95% confidence interval (CI). Results Fourteen studies, on a total of 13,238 RRMS patients, were included in the meta-analysis. All studies but two reported a consistent effect of immunomodulatory treatment on long-term disease progression; the pooled effect on progression to EDSS 6 or SP was significant (p<0.01) when tested by the non-parametric test. The quantitative estimate of the treatment effect in reducing progression to EDSS 6 in the subset of studies reporting this outcome was HRpooled=0.49 (95% CI: 0.34-0.69), p<0.001. Conclusions Treatment with immunomodulators seems to reduce long-term probability of disability progression. Additional well-designed observational studies could help to confirm these findings.