Effectiveness of Nusinersen in Type 1, 2 and 3 Spinal Muscular Atrophy: Croatian Real-World Data

Abstract

(1) Background: To investigate the real-world effectiveness and safety profile of nusinersen in Croatian paediatric and adult spinal muscular atrophy (SMA) patients. (2) Methods: A retrospective and anonymous collection of relevant demographic and clinical data for all Croatian SMA patients treated with nusinersen and reimbursed by the Croatian Health Insurance Fund (CHIF) between April 2018 and February 2022 was performed through searching the CHIF database and studying the associated reimbursement documentation. All patients who received at least one dose of nusinersen were included in the baseline clinical-demographic overview and safety analysis, whereas only subjects who had completed six doses were included in the effectiveness analysis. (3) Results: Fifty-two patients [61.5% male; median age 13.4 (0.1–51.1) yr.] received nusinersen treatment. In SMA type 1 and type 3 paediatric patients, statistically significant motor function improvement (CHOP INTEND 10.8 ± 10.3 vs. 20.0 ± 15.8, p = 0.003; HFMSE 49.6 ± 7.9 vs. 53.1 ± 7.7, p = 0.008; respectively) was achieved immediately after 4 loading doses of nusinersen and remained statistically significant onwards. Average improvements in HFMSE motor performance in SMA type 2 patients after four, five, and six doses of nusinersen were +6.0, +10.5, and +11.0 points, respectively. In SMA type 3 adult patients, no significant improvement in RHS motor performance or the 6-Minute Walk Test (MWT) was demonstrated. During the study period, 437 doses were administered without any new safety concerns appearing. (4) Conclusions: Our RWD findings indicate that nusinersen is an effective and safe treatment in a heterogeneous group of paediatric patients with all types of SMA; however, no significant benefit (but only RHS and 6MWT maintenance) was demonstrated in SMA type 3 patients who started nusinersen after >18 years of age.

Switching from Nusinersen to Risdiplam: A Croatian Real-World Experience on Effectiveness and Safety

“…We have again demonstrated nusinersen’s effectiveness (motor function improvement) in SMA 1 and SMA 3a, whilst its effectiveness was again questionable in the SMA 3p subpopulation, where we can talk about motor function preservation only ( Figure 1 A–C). Those observations confirmed our previous conclusions provided from our bigger real-word nusinersen cohort, that we recently published in the Journal of Clinical Medicine [ 14 ]. Our study clearly demonstrated risdiplam as a non-inferior treatment option, when compared to nusinersen in SMA 1, SMA 3p, and SMA 3a subpopulations ( Table 2 ).…”

“…By presenting this data, we are once again supporting SMA orphan drugs’ efficacy and safety on a wider, heterogenous sample (compared to RCT models in rare diseases), as well as gaining and providing further insights with DMT individualisation, switch, and comparisons [ 14 ]. Besides being important for regulatory issues (pricing, reimbursement, and potential shift of available financial resources), by providing experience and concrete evidence it also upgrades SMA patients’ clinical care, quality of life, and options for management if/when the ineffectiveness or ADRs of primary introduced DMT arise.…”

“…Since this was a retrospective observational study using already collected and aggregated data within the CHIF database and standardised reimbursement documentation, the reported results should be reported accordingly. Unfortunately, due to the high prevalence of scoliosis and spinal fusion among the SMA 2 patients (as it can also be seen from our previous report) they were only occasionally candidates for nusinersen and/or started risdiplam through compassionate use very early, so they did not meet our prespecified inclusion criteria from several reasons; thus, we here only provide scientific evidence for SMA 1, SMA 3p, and SMA 3a [ 14 ]. However, since we have proven non-inferiority in SMA 1 and SMA 3, bearing in mind the clinical and pathophysiological characteristics, we are confident that our safety and effectiveness conclusions can be easily extrapolated to the SMA 2 subpopulation also.…”

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy

“…Subsequent real-life studies with type 1 SMA patients, including those using the drug in an expanded access program, further confirmed the positive effects of nusinersen on motor and respiratory function, as well as on the survival of patients with long-term illness and varying respiratory conditions. 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 …”

Use of the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) in Spinal Muscular Atrophy

“…The use of real-world data, such as those applied in our study, has been shown to offer insights that help to enlighten changing natural history, advance the standard of care and bridge the gap between research and real life. Such studies have noted the potential value of obtaining information on the quality of everyday lives, as we strived to do in our study [16].…”