Abstract
Background and objectiveSphingosine-1-phosphate (S1P) receptors are extensively used in the treatment of multiple sclerosis (MS). However, the optimal therapeutic role of S1P in MS patients has still remained elusive. This network meta-analysis (NMA) systematically evaluated the efficacy and acceptability of S1P receptors, as disease-modifying drugs, in the treatment of patients with MS, so as to find out the most appropriate therapeutic strategy and provide a reliable basis for the prescription of S1P drugs for patients with MS.MethodsWe conducted a systematic review and NMA to compare the efficacy and acceptability of S1P receptors for treating MS patients. Randomized controlled trials (RCTs), which were published until May 2020, were retrieved from the PubMed, Cochrane Library, Embase, and ClinicalTrials.gov databases. The primary outcome in this study was the treatment efficacy for the S1P receptor for MS patients, in terms of decrease in annualized relapse rate. The secondary outcomes were adverse events leading to discontinuation of a study, such as an unfavorable or unintended sign/symptom. Outcomes were appraised using a random effects model expressed as standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs), respectively, and were ranked using surface under the cumulative ranking curve (SUCRA) probabilities for hierarchical clustering of interventions.ResultsA total of 13 RCTS were included, which enrolled 10,554 patients. The results of NMA showed that Fingolimod, Laquinimod, Siponimod, Ozanimod, Amiselimod, and Ponesimod were superior to placebo in terms of reducing the annualized relapse rate of MS patients. Regarding efficacy, the best and worst treatments were Amiselimod (0.4 mg; SUCRA 8.1%) and placebo (SUCRA 90.5%), respectively. As for acceptability, the best and worst interventions were Ozanimod (1 mg; SUCRA 20.4%) and Ponesimod (40 mg; SUCRA 96.0%), respectively. The comparison-adjusted funnel plots of annualized relapse rate and side effects in the included studies revealed that there was no significant funnel plot asymmetryConclusionsThis NMA indicated that Amiselimod (0.4 mg) is the most effective treatment strategy as a S1P receptor for MS patients. However, the abovementioned findings need to be further confirmed in the next researches.
Highlights
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), in which inflammation, demyelination, and axonal loss occur in even early stages of the disease
Efficacy: the result of each cell is the outcome of comparing a drug in the vertical cell with a drug in the horizontal cell (MD)
Acceptability: the result of each cell is the outcome of comparing a drug in the horizontal cell with a drug in the vertical cell (RR)
Summary
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), in which inflammation, demyelination, and axonal loss occur in even early stages of the disease. The aim of MS therapy is to regulate the immune system, control inflammation, reduce recurrence, and attenuate the severity of pain caused by neurological. Fingolimod (FTY720) is the first oral treatment for MS. It binds to sphingosine 1-phophate receptors on lymphocytes and via downregulation of the receptor that prevents lymphocyte egress from lymphoid tissues into the circulation. The optimal therapeutic role of S1P in MS patients has still remained elusive This network meta-analysis (NMA) systematically evaluated the efficacy and acceptability of S1P receptors, as disease-modifying drugs, in the treatment of patients with MS, so as to find out the most appropriate therapeutic strategy and provide a reliable basis for the prescription of S1P drugs for patients with MS
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