Wynn Daniel, Lategan Thomas W, Sprague Tiffany N, Rousseau Franck S, Fox Edward J
Consultants in Neurology, Ltd, Northbrook, IL 60062, USA.
Banner Life Sciences, 3890 Premier Dr., Suite 110, High Point, NC 27265, USA.
Mult Scler Relat Disord. 2020 Oct;45:102335. doi: 10.1016/j.msard.2020.102335. Epub 2020 Jun 25.
Monomethyl fumarate (MMF) is the pharmacologically active metabolite of dimethyl fumarate (DMF). MMF formulated as Bafiertam™ 190 mg and DMF formulated as Tecfidera 240 mg deliver bioequivalent exposure of MMF and therefore possess the same efficacy/safety profiles. DMF is a widely used oral treatment for relapsing-remitting forms of multiple sclerosis (RRMS) but is limited in some patients, primarily female, by issues with gastrointestinal (GI) tolerability.
This was a randomized, double-blind, head-to-head, 5-week study evaluating the GI tolerability of MMF 190 mg vs DMF 240 mg, administered twice daily in healthy subjects, using a derivative of the self-administered Modified Overall Gastrointestinal Symptom Scale (MOGISS). Subjects were stratified (3:1, female:male) and randomized (1:1) to the treatments. The primary endpoint was the Area Under the Curve (AUC) in each of the individual symptoms in the MOGISS over the 5-week treatment period. Other endpoints included the AUC over the 5-week treatment period in the MOGISS composite and total scores; duration and severity of GI events; Number and percentage of subjects reporting GI events during the overall treatment period, and assessment of safety/tolerability.
Inferential analysis of the hierarchical testing of overall treatment differences in each MOGISS symptom AUC occurred in a predefined sequence starting with Abdominal Pain. For each symptom, LSMean AUC values were lower for MMF than DMF, however, the first primary endpoint, Abdominal Pain, was not statistically different between treatments; thus, all subsequent statistical analyses were considered exploratory. The side effects and safety profiles observed were consistent with the known profiles of DMF, with no new or unique safety concerns noted.
Bafiertam showed an improved gastrointestinal tolerability profile compared with Tecfidera, with less severe GI events and fewer days of self-assessed GI symptoms, fewer GI adverse events, and lower discontinuation rates because of GI adverse events.
富马酸单甲酯（MMF）是富马酸二甲酯（DMF）的药理活性代谢产物。以Bafiertam™ 190毫克制剂形式存在的MMF和以Tecfidera 240毫克制剂形式存在的DMF可提供生物等效的MMF暴露量，因此具有相同的疗效/安全性特征。DMF是复发缓解型多发性硬化症（RRMS）广泛使用的口服治疗药物，但在一些患者（主要是女性）中，由于胃肠道（GI）耐受性问题而受到限制。
这是一项随机、双盲、头对头的5周研究，使用自我管理的改良总体胃肠道症状量表（MOGISS）的衍生量表，评估190毫克MMF与240毫克DMF在健康受试者中每日两次给药时的胃肠道耐受性。受试者按性别分层（女性：男性为3:1）并随机（1:1）接受治疗。主要终点是在5周治疗期内MOGISS中各单项症状的曲线下面积（AUC）。其他终点包括5周治疗期内MOGISS综合评分和总分的AUC；胃肠道事件的持续时间和严重程度；在整个治疗期间报告胃肠道事件的受试者数量和百分比，以及安全性/耐受性评估。
对每个MOGISS症状AUC的总体治疗差异进行分层检验的推断性分析按预先定义的顺序进行，从腹痛开始。对于每个症状，MMF的最小二乘均数AUC值低于DMF，然而，第一个主要终点腹痛在治疗组之间无统计学差异；因此，所有后续统计分析均被视为探索性分析。观察到的副作用和安全性特征与DMF的已知特征一致，未发现新的或独特的安全问题。
与Tecfidera相比，Bafiertam显示出更好的胃肠道耐受性，胃肠道事件较轻，自我评估的胃肠道症状天数较少，胃肠道不良事件较少，因胃肠道不良事件导致的停药率较低。
