Interferon-beta for relapsing-remitting multiple sclerosis: a systematic review

Abstract

Objective To assess the efficacy and safety of interferon-beta (IFN-β) as monotherapy versus placebo for patients with relapsing-remitting multiple sclerosis (RRMS).  Methods We searched Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, CINAHL, LILACS, PEDRO, China Biology Medicine Disc (CBMDisc), as well as clinical trial registries and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP, retrieval deadline: June 2014). Furthermore, we checked reference lists of published reviews and retrieved articles, and communicated personally with investigators and biotechnology companies participating in trials of IFN-β in an effort to identify further studies or unpublished data. Two review authors independently screened studies, extracted data and evaluated the risk of bias. Formal Meta-analysis were conducted by using Review Manager software (Version 5.3.3) and the impacts of limitations in study design or execution (risk of bias), inconsistency in results, imprecision of results, indirectness of evidence and publication bias on the quality of the body of evidence were assessed.  Results A total of 576 articles were retrieved. After screening of titles and abstracts, 26 studies were provisionally selected. The full text of papers were obtained for further assessment of eligibility. Finally, 5 studies were included, involving 2129 patients with RRMS (high-dose IFN-β group: N = 1076; placebo group: N = 1053). All studies were randomized, double-blind, controlled, parallel-group clinical trials with a follow-up for at least one year, evaluating IFN-β versus placebo as monotherapy for patients with RRMS. Most studies had methodological limitations, mainly on a high risk of attrition bias. Moreover, the intention to treat (ITT) principle was not used in data analysis. Data from only 919 patients (43.17%) were available to calculate the primary outcomes at 2 years of follow-up. Meta-analysis indicated IFN-β slightly reduced the number of patients with at least one relapse [risk ratio (RR) = 0.810, 95%CI: 0.740-0.890; P = 0.000] and the number of patients with disability progression during the first 2 years of follow-up (RR = 0.700, 95%CI: 0.550-0.880; P = 0.002). However, the sensitivity analysis (worst-case scenario analysis) showed no treatment effect (RR = 1.110, 95%CI: 0.730-1.680, P = 0.620; RR = 1.310, 95%CI: 0.600-2.890, P = 0.500, respectively). Data from 1581 patients (74.26%) were available to analyze the number of patients with at least one relapse during the first year of follow-up (RR = 0.740, 95% CI: 0.590-0.930; P = 0.010). Absolute risk reduction (ARR) was 13.24% and number needed to treat (NNT) was 8, which meant 8 patients were needed to treat to prevent one patient against relapse. However, the pooled results showed no treatment effect on the annualized relapse rate. The adverse events frequently caused by IFN-β included injection-site reactions, chills, pyrexia, myalgia, influenza-like symptoms, headache, increased alanine aminotransferase (ALT) and increased aspartate aminotransferase (AST). However, the incidences of lymphocytopenia, leucopenia, depression and committed or attempted suicide were not significantly increased by IFN-β.  Conclusions There is high-quality evidence to support that IFN-β slightly reduces the number of patients with RRMS having relapse during the first year of follow-up, but the clinical effect beyond one year is uncertain. There is insufficient evidence to determine the efficacy of IFN-β in reducing the number of patients with disability progression. New randomized controlled trials of high quality are needed to assess the long-term efficacy.

doi: 10.3969/j.issn.1672-6731.2014.09.007