Different Doses of Fingolimod in Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Xin Wu; Tao Xue; Zilan Wang; Zhouqing Chen; Xuwei Zhang; Wei Zhang; Zhong Wang

doi:10.3389/fphar.2021.621856

Different Doses of Fingolimod in Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Front Pharmacol. 2021 May 17:12:621856. doi: 10.3389/fphar.2021.621856. eCollection 2021.

Authors

Xin Wu^{1

2}, Tao Xue¹, Zilan Wang¹, Zhouqing Chen¹, Xuwei Zhang³, Wei Zhang², Zhong Wang¹

Affiliations

¹ Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Neurosurgery, Suzhou Ninth People's Hospital, Suzhou, China.
³ Department of Neurosurgery, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang, China.

Abstract

Background: The efficacy and safety of fingolimod for relapsing-remitting multiple sclerosis (RRMS) had been well verified in several large randomized controlled trials (RCTs) during the past decade. However, there are fewer systematic comparisons of different doses of fingolimod and whether the dose of 0.5 mg/d is the optimal one still remains to be solved. Objective: The objective of this systematic review was to evaluate the efficacy and safety of the four existing doses of fingolimod in the treatment of RRMS, especially the dose of 0.5 mg/d. Methods: MEDLINE, EMBASE, Cochrane Library, and clinicaltrials.gov were searched for RCTs which were performed to evaluate different doses of fingolimod and the corresponding control (placebo or DMTs) up to October 2020. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and mean difference (MD) was analyzed and calculated with a random effect model. Results: We pooled 7184 patients from 11 RCTs. Fingolimod 0.5 mg/d was superior to control group in all eight efficacy outcomes including annualized relapse rate (ARR) (MD -0.22, 95%CI -0.29 to -0.14, p < 0.00001) but surprisingly showed a higher risk of basal-cell carcinoma (RR 4.40, 95%CI 1.58 to 12.24, p = 0.004). Although 1.25 mg/d is more than twice the dose of 0.5 mg/d, the effect size was almost similar between them. Dose of 5 mg/d obtained an unsatisfactory efficacy while showing a greater risk of adverse events than other three doses (RR 1.17, 95%CI 1.05 to 1.30, p = 0.003). Additionally, fingolimod 0.25 mg/d not only showed a better performance in delaying the disease progress of magnetic resonance imaging (MRI), but also achieved a certain degree of patient treatment satisfaction. Conclusion: At present, 0.5 mg/d remains to be the optimal dose of fingolimod for RRMS patients but trials of a lower dose are still of great clinical significance and should be paid more attentions.

Keywords: different doses; fingolimod; multiple sclerosis; relapsing-remitting; systematic review.