Treatment expectations and patient-reported outcomes of nusinersen therapy in adult spinal muscular atrophy

Abstract

Background The antisense-oligonucleotide (ASO) nusinersen has recently been approved as the first genetically modifying therapy for 5q-associated spinal muscular atrophy (SMA) based on randomized sham-controlled trials in infants and children. The efficacy in adults with long disease history and advanced disease status is still widely unknown; the same applies to specific expectations of adult SMA patients and to what extent they are met and may impact outcome measures. Methods In a longitudinal monocentric study in adult patients with SMA types 2-4, the Stanford Expectations of Treatment Scale (SETS) was assessed prior to and during nusinersen treatment. Treatment outcome was evaluated using patient-reported outcomes (PROs) as well as objectively quantifiable motor outcome measures. Results Adult SMA patients had high expectations of nusinersen treatment effectiveness regarding increase in muscle strength and disease stabilization. Via PROs, 75% stated improvements in muscle strength, endurance and independence under therapy which was in line with slight improvements in quantifiable motor scores during a ten month observation period. In contrast, patients only expressed few negative expectations which further decreased during therapy. Conclusions This study showed mainly positive treatment expectations and PROs in patients undergoing nusinersen treatment along with measurable functional improvement in adult SMA patients. Moreover, treatment expectations did not significantly influence outcome measures. Keywords Spinal muscular atrophy (SMA) • Patient-reported outcomes (PROs) • Stanford expectations of treatment scale (SETS) • Nusinersen • Antisense-oligonucleotide (ASO)

Treatment satisfaction in 5q-spinal muscular atrophy under nusinersen therapy

“…Besides improvement in muscle strength, SMA patients considered mobility, endurance, and disease stabilization as relevant treatment outcomes in a previous study. 32 Early high treatment satisfaction could therefore already arise from the interruption of further disease progression. As TSQM-1.4 © lacks qualitative analyses, the exact causes underlying patients’ satisfaction with effectiveness remain to be further elucidated.…”

Nusinersen Wearing-Off in Adult 5q-Spinal Muscular Atrophy Patients

“…Comparing patients repeatedly reporting wearing-off to those with no experienced diminishing effects, the BMI was significantly higher in patients with wearing-off phenomena. Interestingly, in a previous study, we already identified that patients with a higher BMI more frequently reported a deterioration of symptoms during the treatment course [ 21 ]. Higher BMI, however, is not associated to an increased CSF volume [ 22 ].…”

Cognitive Performance of Patients with Adult 5q-Spinal Muscular Atrophy and with Amyotrophic Lateral Sclerosis

“…SMA patients ( n = 51) with genetically confirmed mutations in the SMN1 gene were screened between 16 May 2017 and 15 October 2019 at both sites and ALS patients ( n = 67) between 23 April 2015 and 13 June 2018 at MHH only. All enrolled SMA patients received therapy with the antisense oligonucleotide nusinersen [ 26 , 27 ]. Inclusion criteria for all patients were age ≥ 18 years and ability to perform cognitive function testing in a structured personal interview.…”