A Meta-analysis On Efficacy And Safety Of Teriflunomide For Multiple Sclerosis

Objective: To assess the efficacy and safety of teriflunomide(TFN)in contrast to placebo in multiple sclerosis(MS)patients.Methods:All published randomized controlled trials(RCTs)of teriflunomide for MS were identified by searching the electronic databases(Pub Med,EMBASE,Cochrane Library,CBMdise,CNKI)and relevant journals from the origination dates to February,2018.The selection of studies,evaluation of quality and extraction of data were conducted by two independent reviewers.The Cochrane risk-of-bias tool was used to assess the methodological quality of included RCTs.A sensitivity analysis was performed on the primary outcomes to assess the stability of our results.The Stata 12.0 software was employed for meta analysis.The evaluation index by 95% confidence interval was estimated and the size of test was set for 0.05.Results:Six studies were included in the review,totally involving 3293 patients,of which four compared teriflunomide(7mg·d-1 and 14mg·d-1)with placebo,two presented with two dosages of teriflunomide added-on to interferon-beta or glatiramer acetate in MS treatment.All studies shared a middle quality.Our results showed that both dosages of teriflunomide were more effective than placebo in reducing the ARR(7mg: RR=0.72,95%CI: 0.65-0.80;14mg: RR=0.67,95%CI: 0.61-0.75,both P<0.0001),the incidence of at least one relapse(7mg: RR=0.78,95%CI: 0.70-0.87;14mg: RR=0.69,95%CI: 0.61-0.77;both P<0.0001)and improving active MRI measures in T1-Gd enhancing lesions(7mg: RR=0.78,95%CI: 0.71-0.86;14mg: RR=0.64,95%CI: 0.58-0.72,both P<0.0001).Only teriflunomide 14 mg alleviated the progression of disability compared to placebo(14mg: RR=0.69,95%CI: 0.55-0.87,P=0.002)and was superior to 7mg in improving active MRI measures(7mg vs.14mg: RR=1.21,95%CI: 1.08-1.37,P=0.002).The incidence of adverse events(AEs)and serious adverse events were similar in all treatment groups,while the incidence of study discontinuation because of AEs was higher in teriflunomide groups compared placebo(7mg: RR=1.47,95%CI: 1.12-1.92,P=0.005;14mg: RR=1.63,95%CI: 1.25-2.13,P<0.0001).The most common AEs were mild to moderate,including elevated alanine aminotransferase(ALT)levels,hair thinning,diarrhea,nausea and fatigue.A dose-related effect existed in the safety and efficacy profiles.The sensitive analysis got the most similar results and suggested that the initial meta analysis results stable.Conclusions:Both doses of teriflunomide could significantly reduce relapses and active MRI measures with a similar and acceptable safety profile compared to placebo.Teriflunomide 14 mg is more desirable for MS patients due to its ability on reducing disability progression.There are some limitations in our review and caution should be taken in the clinical practice.