Motor function in type 2 and 3 SMA patients treated with Nusinersen: a critical review and meta-analysis

Abstract

Background There is an increasing number of papers reporting the real world use of Nusinersen in different cohorts of SMA patients. Main body The aim of this paper was to critically review the literature reporting real world data on motor function in type 2 and 3 patients treated with Nusinersen, subdividing the results according to SMA type, age and type of assessment and performing a meta-analysis of the available results. We also report the available data collected in untreated patients using the same measures. Of the 400 papers identified searching for Nusinersen and spinal muscular atrophy, 19 reported motor function in types 2 and 3: 13 in adults, 4 in children and 2 included both. Twelve papers reported untreated patients’ data. All studies reported positive changes on at least one of the functional measures and at every time point while all-untreated cohorts showed negative changes. Conclusion Our review suggests that Nusinersen provides a favorable benefit in motor function across a wide range of SMA type 2 and 3 patients over a 10–14 month observation period. Although a direct comparison with studies reporting data from untreated patients cannot be made, the longitudinal changes in the treated cohorts (consistently positive) are divergent from those observed in the untreated cohorts (consistently negative). The difference could be observed both in the global cohorts and in smaller groups subdivided according to age, type or functional status.

Nusinersen efficacy data for 24‐month in type 2 and 3 spinal muscular atrophy

“…Our results confirm the previously reported increase in motor function after 12 months of nusinersen treatment 5,7,9,10,20 but also show that further improvement, even if smaller, can also be observed in the second year. The increase was more obvious on the HFMSE, with changes reaching significance already after 12 months in type 2.…”

“…The advantage of the present study is that we not only had a much larger cohort of treated patients, but also a suitable large comparator group of untreated patients in different age subgroups available from recent natural history studies. [18][19][20][21][22] The comparison was possible because both treated and natural history cohorts had been assessed by the same clinical evaluators using the same measures.…”

Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial

“…SMA type 3 causes less severe disability than SMA type 2, with patients being able to stand and walk independently, although with increasing difficulty as they age. Patients with SMA type 3 have later symptom onset and develop fewer and less severe musculoskeletal, respiratory, and feeding problems 7 , 8 , 10 – 12 . Considerable heterogeneity within this clinical framework exists 10 , 11 .…”

“…Patients with SMA type 3 have later symptom onset and develop fewer and less severe musculoskeletal, respiratory, and feeding problems 7 , 8 , 10 – 12 . Considerable heterogeneity within this clinical framework exists 10 , 11 . Observational studies of SMA type 2 and type 3 use continuous variables such as measures of motor performance, upper limb strength and activity, pulmonary function, and compound motor action potential (CMAP) 7 , 8 , 12 – 15 .…”

Spinal muscular atrophy: Surviving respiratory failure, intensive care and pursuing creatively fulfilled life

“…Advances in respiratory support seem to have brought down mortality 4 . In untreated SMA type II, the course of the disease is slower to progress and life expectancy is lower than the healthy population 5 . Fortunately, Hong Kong has devoted expert physicians and allied health colleagues caring for these children with special needs.…”