Sitting in patients with spinal muscular atrophy type 1 treated with nusinersen

Abstract

Aim To determine factors associated with acquisition of a sitting position in patients with spinal muscular atrophy type 1 (SMA1) treated with nusinersen. Method Using data from the registry of patients with SMA1 treated with nusinersen, we compared the subgroups of sitters and non‐sitters after 14 months of therapy as a function of baseline level, SMN2 copy number, age at treatment initiation, and improvement at 2 and 6 months post‐treatment initiation. We used Hammersmith Infant Neurological Examination, Section 2 (HINE‐2) and Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders for motor evaluation. Results Fifty children (22 females, 28 males), mean age 22 months (SD 20.7; range 2.5–102.8mo) were treated. Data on sitting position acquisition were collected for 47 patients at month 14. Fifteen patients were able to sit unassisted; 11 of 15 had a baseline HINE‐2 score of at least 2 points and 11 of 14 had an improvement over baseline of at least 2 points at month 6. Patients who improved by 2 or more points at month 6 were three times more likely to be sitters at month 14 than those who did not. Interpretation High baseline motor function and improvement in HINE‐2 score after 6 months of treatment are associated with the probability of acquiring a sitting position in patients with SMA1 treated with nusinersen. What this paper adds Fifteen of 47 patients with spinal muscular atrophy could sit unaided 14 months after treatment with nusinersen. The number of SMN2 copies were not predictive of acquisition of a sitting position. Baseline condition and clinical response after 6 months of treatment were most predictive of sitting position acquisition.

European ad-hoc consensus statement on gene replacement therapy for spinal muscular atrophy

“…This improvement is exceptional in symptomatic children with SMA type 1 and may be misleading both for some parents of much more affected children, and for clinicians who are not deeply involved in this field of research. For treatment with Nusinersen Aragon-Gawinska et al have shown that higher baseline motor function is associated with higher probability of acquisition of motor milestones [13]. At the other end of the spectrum, more severely affected patients, who do already depend on respiratory support and tube feeding at initiation of treatment, do in most cases only demonstrate very modest improvement if at all [14e16].…”

<p>Advances in Newborn Screening and Presymptomatic Diagnosis of Spinal Muscular Atrophy</p>

“…The effectiveness of treatment observed in randomized drug trials is confirmed by the results of open clinical trials and real-world data. [12][13][14][15][16][17] In drug trials, 323 patients with various forms of SMA (SMA1, 2, 3 and presymptomatic) were treated with nusinersen. Currently, over 11,000 patients worldwide receive the drug (October 2020).…”

“…Real-world data indicate that up to 30% of symptomatically treated SMA1 patients (15/47 in the group treated for 14 msc, aged 2.5-102.8 msc and 2/61 and 3/16 treated for 6 msc) achieved sitting ability. 15,16,24 Thus, the ability to achieve independent sitting in children with SMA1 treated symptomatically with nusinersen might be estimated at 30-50%, depending on the age of treatment initiation. This efficacy of symptomatic treatment is incomparably lower than the results of presymptomatic treatment.…”

Przegląd metod oceny funkcjonalnej analizujących motorykę małą i dużą u chorych z rdzeniowym zanikiem mięśni

“…Dziecko musi być badane najlepiej rano, kiedy jest ożywione. Dozwolone są trzy próby wykonywania danej czynności [2,10].…”