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.

Keywords: Critical review; Nusinersen; Spinal muscular atrophy.

Fig. 1

Search and selection process (PRISMA framework)

Fig. 2

Hammersmith Functional Motor Scale Expanded results reporting author, HFMSE results (0–66 scale, mean ± SD), sample size, mean age (years, range/SD), mean baseline HFMSE (range/SD). a Adult population, b pediatric population. Key to figure: dashed line = 95% Confidence interval, plain line = Standard Deviation, square = SMA 2, circle = SMA 3, diamond = ambulant SMA 3, triangle = non ambulant SMA 3, square + circle + triangle = mix phenotypes. Bold font = Median value, Italic = Mean value. Color coding: light blue =  ~10 months from initiation of drug, Red =  ~12 months from initiation of drug, Green =  ~24 months from infusion. Grey shade = SMA 2, White shade = SMA 3, Striped shade = mixed phenotypes. *Mean/median values of the baseline population non excluding drop-outs at T10, 14 or 24 months of follow-up, **mean/median values of the baseline population of both SMA II and III combined

Fig. 3

Revised Upper Limb Module results reporting author, results (mean ± SD), sample size, mean age (years, range/SD), mean baseline RULM (range/SD). a Adult population, b pediatric population. Key to figure: dashed line = 95% Confidence interval, plain line = Standard Deviation, square = SMA 2, circle = SMA 3, diamond = ambulant SMA 3, triangle = non ambulant SMA 2, square + circle + triangle = mix phenotypes. Bold font = Median value, Italic = Mean value. Color coding: light blue =  ~10 months from infusion, Red =  ~12 months from infusion, Green =  ~24 months from infusion. Grey shade = SMA 2, White shade = SMA 3, Striped shade = mixed phenotypes. *Mean/median values of the baseline population non excluding drop-outs at T10, 14 or 24 months of follow-up, **mean/median values of the baseline population of both SMA II and III combined

Fig. 4

6 min-Walk Test results reporting author, results (mean ± SD), sample size, mean age (years, range/SD), mean baseline 6MWT (range/SD). a Adult population, b pediatric population. Key to figure: dashed line = 95% Confidence interval, plain line = Standard Deviation. Bold font = Median value, Italic = Mean value. Color coding: light blue =  ~10 months from infusion, Red =  ~12 months from infusion. *Mean/median values of the baseline population non excluding drop-outs at T10, 14 or 24 months of follow-up, **mean/median values of the baseline population of both SMA II and III combined