背景:生物素可能激活乙酰辅酶A-,3-甲基巴豆酰基-CoA-,丙酰基-CoA-,和丙酮酸羧化酶,以增加髓鞘修复和/或合成,并可能增强三磷酸腺苷(ATP)的产生,这对预防神经变性可能是必不可少的。本综述的目的是通过对随机对照试验的系统评价,确定高剂量生物素(HDB)在多发性硬化症中的有效性和安全性。
方法:我们在以下电子数据库中搜索了相关文章:MEDLINE,中部,EMBASE,Scopus,和ClinicalTrials.gov网站,直到2021年4月。我们考虑了随机临床试验(RCT),该试验涉及诊断为符合McDonald2010/2017标准或Lublin2014标准的任何多发性硬化症表型的成年患者。我们纳入了使用高剂量生物素或“MD1003”的研究,口服至少300mg/天,并给予至少三个月。使用Cochrane偏差风险(RoB)工具对纳入研究的方法学质量评估。等级方法用于评估证据的确定性[COE]。
结果:在确定的366条记录中,纳入3项RCT,包括889名被诊断为MS的个体(830名参与者有进展性MS(PMS);59名参与者有RRMS),用于分析.总体女性:男性比例为1.16:1。所有纳入的试验均使用HDB作为辅助治疗。三项研究中的偏倚风险在所有领域都很低。在12到15个月,没有足够的证据表明HDB和安慰剂组在MS相关残疾的综合改善方面存在差异(相对风险(RR)2.87;95%CI0.29-28.40;2项试验;796名参与者;I2=66%)[低COE],扩展残疾状况量表(IEDSS)的改善(RR2.27;95%CI0.25-20.98;2项试验;796名参与者;I2=63%)[低COE],在PMS患者中,IEDSS和25英尺步行时间(ITW25)(IEDSS-ITW25)(RR0.58;95%CI0.17-2.00;2项试验;796名参与者;I2=13%)[中度COE]。12至15个月ITW25的汇总数据具有统计学意义(RR2.06;95%CI1.04-4.09;2项试验;796名参与者;I2=0%)[中度COE]有利于PMS患者的HDB。在12到15个月,在PMS患者中,EDSS的平均变化无显著差异(MD-0.06;95%CI-0.14-0.02;2项研究;796名参与者;889名参与者;I2=68%).任何AE发生率的综合数据(RR0.98;95%CI0.92-1.04;3项试验;I2=0%)[高COE]和任何严重AE(RR0.98;95%CI0.77-1.24;3项试验;889名参与者;I2=0%)[中度COE]在HDB组和安慰剂组之间没有显着差异。在HDB组的662名合并患者中,与合并安慰剂组的零事件相比,发现31名患者(4.7%)具有实验室测试干扰[高COE]。
结论:证据的适度确定性表明,就ITW25而言,在PMS患者中,支持HDB给药12至15个月的潜在益处。然而,这种益处的一个重要权衡是,证据的高度确定性表明,在进行HDB时,实验室测试干扰的发生率增加.
BACKGROUND: Biotin may activate the acetyl-CoA-, 3-methylcrotonyl-CoA-, propionyl-CoA-, and pyruvate carboxylases to increase myelin repair and/or synthesis, and may enhance the production of adenosine triphosphate (ATP), which may be essential to prevent neurodegeneration. The purpose of this
review was to determine the effectiveness and safety of high-dose
biotin (HDB) in multiple sclerosis via a systematic
review of randomized controlled trials.
METHODS: We searched the following electronic databases for relevant articles: MEDLINE, CENTRAL, EMBASE, Scopus, and ClinicalTrials.gov website until April 2021. We considered randomized clinical trials (RCTs) that involved adult patients diagnosed with any phenotype of multiple sclerosis that conforms with the McDonald 2010/2017 criteria or the Lublin 2014 criteria. We included studies employing high-dose
biotin or \"MD1003\" administered orally for at least 300 mg/day and given for at least three months. The methodological quality assessment of the included studies was done using the Cochrane Risk of Bias (RoB) tool. The GRADE approach was used to assess the certainty of evidence [COE].
RESULTS: Out of 366 records identified, three RCTs involving 889 individuals diagnosed with MS (830 participants had progressive MS (PMS); 59 had RRMS) were pooled for analyses. The overall female:male ratio was 1.16:1. All included trials used HDB as an adjunctive treatment. The risks of bias in the three studies were low across the domains. At 12 to 15 months, there is insufficient evidence that the HDB and placebo arms differed in terms of composite improvement of MS-related disability (relative risk (RR) 2.87; 95% CI 0.29-28.40; 2 trials; 796 participants; I2 = 66%) [low COE], improvement in expanded disability status scale (IEDSS) (RR 2.27; 95% CI 0.25-20.98; 2 trials; 796 participants; I2 = 63%) [low COE], and both IEDSS and improvement in 25-foot walk time (ITW25) (IEDSS-ITW25) (RR 0.58; 95% CI 0.17-2.00; 2 trials; 796 participants; I2 = 13%) [moderate COE] among patients with PMS. Pooled data for ITW25 at 12 to 15 months yielded statistical significance (RR 2.06; 95% CI 1.04-4.09; 2 trials; 796 participants; I2 = 0%) [moderate COE] favoring HDB among patients with PMS. At 12 to 15 months, no significant differences were found in terms of mean change in EDSS (MD -0.06; 95% CI -0.14-0.02; 2 studies; 796 participants; 889 participants; I2 = 68%) among patients with PMS. Synthesized data on incidence of any AEs (RR 0.98; 95% CI 0.92-1.04; 3 trials; I2 = 0%) [high COE] and any serious AEs (RR 0.98; 95% CI 0.77-1.24; 3 trials; 889 participants; I2 = 0%) [moderate COE] were not significantly different between HDB and placebo groups. Out of 662 pooled patients in the HDB group, 31 patients (4.7%) were found to have laboratory test interference compared to zero event in the pooled placebo group [high COE].
CONCLUSIONS: A moderate certainty of evidence suggests a potential benefit in favor of HDB administered for 12 to 15 months in terms of ITW25 in patients with PMS. However, an important trade-off of this benefit is the high certainty of evidence suggesting an increased incidence of laboratory test interference when HDB is taken.