Abstract
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.
Highlights
Nusinersen has been approved for all 5q-spinal muscular atrophy (SMA) patients based on pivotal phase 3 trials exclusively conducted in infants and children, which showed a so-far never-seen improvement in motor function in this distinct patient group [6,7]
Adults represent a relevant proportion of the overall SMA population, nusinersen tolerability, pharmacokinetics, safety and efficacy have not been investigated in adult SMA patients ahead of approval
Questionnaires that were filled in during the therapy loading period were excluded from the analysis since treatment intervals were short and no clinically meaningful treatment benefits were expected at this early treatment time point (n = 12; time since treatment initiation: two weeks n = 3; one month n = 4 and two months n = 5)
Summary
Nusinersen efficacy in adult SMA has been reported based on multicenter observational trials [8,9,10]. These studies demonstrated a clinically meaningful treatment effect, especially in less severely affected SMA patients, so far classified as SMA type 3. Type 3 patients are characterized by disease onset after 18 months of age and by reaching the motor milestone of being able to walk independently This function can be lost during the disease course, so SMA type 3 comprises a broad clinical continuum [11].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
