Osmanovic Alma, Schreiber-Katz Olivia, Petri Susanne
Department of Neurology, Hannover Medical School, 30625 Hannover, Germany.
Brain Sci. 2021 Mar 13;11(3):367. doi: 10.3390/brainsci11030367.
The antisense oligonucleotide nusinersen was the first drug treatment available for all types of 5q-spinal muscular atrophy (SMA). The dosing regime has been derived from pivotal clinical trials in infants and children. The efficacy of nusinersen in severely affected adult SMA patients is still questionable, as no placebo-controlled trials have been conducted. In the present study, we systematically examined wearing-off phenomena during nusinersen maintenance dosing using a patient-centered approach. We found that adult SMA patients perceived wearing-off after nearly half of 51 investigated nusinersen administrations, primarily within the last month prior to the next administration. Symptoms and functions affected were mainly general strength and arm and leg muscle function next to endurance and independence in daily routine. Lack of walking ability and higher body mass index were characteristic phenotypic features in patients with consistent wearing-off effects. We assume that specific SMA phenotypes might benefit from higher dosing, shorter treatment intervals, change of treatment administration or a combination of all. Efforts towards treatment optimization may result in higher efficacy in distinct phenotypes.
反义寡核苷酸诺西那生是首个可用于治疗所有类型5q脊髓性肌萎缩症（SMA）的药物。给药方案源自针对婴幼儿和儿童的关键临床试验。由于尚未进行安慰剂对照试验，诺西那生在重度成年SMA患者中的疗效仍存疑问。在本研究中，我们采用以患者为中心的方法，系统地研究了诺西那生维持给药期间的药效减退现象。我们发现，在接受调查的51次诺西那生给药中，近半数给药后成年SMA患者察觉到药效减退，主要发生在下一次给药前的最后一个月内。受影响的症状和功能主要包括一般力量、手臂和腿部肌肉功能，以及日常活动中的耐力和独立性。缺乏行走能力和较高的体重指数是出现持续药效减退效应患者的典型表型特征。我们认为，特定的SMA表型可能会从更高剂量、更短治疗间隔、改变给药方式或三者结合中获益。致力于优化治疗的努力可能会在不同表型中产生更高的疗效。
