Tong Jingyi, Zou Qin, Chen Yongmin, Liao Xiaoping, Chen Rong, Ma Lin, Zhang Daqi, Li Qifu
Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Haikou, 570100, People's Republic of China.
Department of Psychology, The First Affiliated Hospital of Hainan Medical University, Haikou, 570100, People's Republic of China.
Neurol Sci. 2021 May;42(5):1687-1695. doi: 10.1007/s10072-021-05049-w. Epub 2021 Feb 1.
Sphingosine-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.
We 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.
A 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 asymmetry CONCLUSIONS: This 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.
1-磷酸鞘氨醇（S1P）受体广泛应用于多发性硬化症（MS）的治疗。然而，S1P在MS患者中的最佳治疗作用仍不明确。本网络荟萃分析（NMA）系统评价了S1P受体作为疾病修正药物治疗MS患者的疗效和可接受性，以找出最合适的治疗策略，并为MS患者使用S1P药物处方提供可靠依据。
我们进行了一项系统评价和NMA，以比较S1P受体治疗MS患者的疗效和可接受性。从PubMed、Cochrane图书馆、Embase和ClinicalTrials.gov数据库中检索截至2020年5月发表的随机对照试验（RCT）。本研究的主要结局是S1P受体对MS患者的治疗效果，以年化复发率的降低来衡量。次要结局是导致研究中止的不良事件，如不良或意外的体征/症状。结局分别采用随机效应模型进行评估，以标准化均数差（SMD）和风险比（RR）表示，并给出95%置信区间（CI），并使用累积排序曲线下面积（SUCRA）概率对干预措施进行分层聚类排序。
共纳入13项RCT，涉及10554例患者。NMA结果显示，芬戈莫德、拉喹莫德、西普尼莫德、奥扎莫德、阿密司莫德和波尼莫德在降低MS患者年化复发率方面优于安慰剂。在疗效方面，最佳和最差治疗分别是阿密司莫德（0.4mg；SUCRA 8.1%）和安慰剂（SUCRA 90.5%）。在可接受性方面，最佳和最差干预分别是奥扎莫德（1mg；SUCRA 20.4%）和波尼莫德（40mg；SUCRA 96.0%）。纳入研究中年化复发率和副作用的比较调整漏斗图显示，漏斗图无明显不对称。
本NMA表明，阿密司莫德（0.4mg）作为S1P受体对MS患者是最有效的治疗策略。然而，上述研究结果需要在后续研究中进一步证实。
