Effectiveness of Nusinersen in Type 1, 2 and 3 Spinal Muscular Atrophy: Croatian Real-World Data
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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SMA Type | Age at Symptom Onset | Maximum Motor Function Achieved | Prognosis |
---|---|---|---|
0 | Prenatal/foetal | Nil | Poor; usually die before 6 months |
1 | <6 months | Non-sitter | Poor; usually die before 2 years |
2 | 7–18 months | Sit independently | Expected to live into their twenties and beyond |
3 | >18 months | Walker | Progressive weakness, motor disability, normal lifespan |
4 | 10–30 yr | Walker | Weakness of lower extremities, normal lifespan |
Baseline Demographics | SMA 1 | SMA 2 | SMA 3p+pa | SMA 3a | SMA 3 Total | Total | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
N (% out of total) | 18 (34.6%) | 6 (11.5%) | 11 (21.1%) | 17 (32.7%) | 28 (53.8%) | 52 (100%) | |||||
Age (years) | X ± SD | 6.3 ± 6.3 | 8.8 ± 6.0 | 12.2 ± 4.6 | 32.4 ± 8.5 | 24.5 ± 12.3 | 16.4 ± 13.2 | ||||
Med (Min-Max) | 5.2 (0.1–20.8) | 10.2 (1.5–16.7) | 13.5 (4.2–17.5) | 30.5 (18–51.1) | 24.8 (4.2–51.1) | 13.4 (0.1–51.1) | |||||
Male/female | 12/6 | 3/3 | 6/5 | 11/6 | 17/11 | 32/20 | |||||
SMN1 exon 7 copy number | 0 | 17 | 5 | 11 | 17 | 28 | 50 | ||||
1 | 1 | 1 | 0 | 0 | 0 | 2 | |||||
SMN1 exon 8 copy number | 0 | 14 | 4 | 7 | 12 | 19 | 37 | ||||
1 | 4 | 2 | 4 | 2 | 6 | 12 | |||||
2 | 0 | 0 | 0 | 3 | 3 | 3 | |||||
SMN2 exon 7 copy number | 1 | 1 | 1 | 0 | 0 | 0 | 2 | ||||
2 | 15 | 1 | 2 | 0 | 2 | 18 | |||||
3 | 2 | 4 | 6 | 4 | 10 | 16 | |||||
4 | 0 | 0 | 3 | 13 | 16 | 16 | |||||
SMN2 exon 8 copy number | 1 | 4 | 1 | 0 | 0 | 0 | 5 | ||||
2 | 12 | 1 | 1 | 4 | 5 | 18 | |||||
3 | 2 | 4 | 6 | 4 | 10 | 16 | |||||
4 | 0 | 0 | 4 | 9 | 13 | 13 | |||||
NAIP copy number | 0 | 9 | 0 | 1 | 0 | 1 | 10 | ||||
1 | 8 | 6 | 2 | 3 | 5 | 19 | |||||
2 | 1 | 0 | 8 | 13 | 21 | 22 | |||||
3 | 0 | 0 | 0 | 1 | 1 | 1 | |||||
Mechanical ventilation—N (% out of total for corresponding SMA type) | 10 (55.6%) | 2 (33.3%) | 0 (0%) | 0 (0%) | 0 (0%) | 12 (23.1%) | |||||
BiPAP—N (% out of total for corresponding SMA type) | 8 (44.4%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 8 (15.4%) | |||||
PEG—N (% out of total for corresponding SMA type) | 4 (22.2%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 4 (7.7%) | |||||
NG tube—N (% out of total for corresponding SMA type) | 8 (44.4%) | 2 (33.3%) | 0 (0%) | 0 (0%) | 0 (0%) | 10 (19.2%) | |||||
Baseline motor function (N of patients) | X ± SD | CHOP INTEND (N = 17) | 9.1 ± 10.1 | HFMSE (N = 4) | 5.8 ± 8.0 | HFMSE (N = 11) | 49.6 ± 7.9 | RHS (N = 15) | 48.5 ± 15.3 | N/A, N = 26 | N/A, N = 47 |
Med (Min-Max) | 5 (0–38) | 3 (0–17) | 51 (29–60) | 52 (19–65) |
Time of Evaluation/Doses Already Received | All SMA Type 1 Patients | SMA Type 1 Patients Not on MV | ||||||
---|---|---|---|---|---|---|---|---|
N of Patients | CHOP INTEND/X ± SD | Change from Baseline | p Value | N of Patients | CHOP INTEND/X ± SD | Change from Baseline | p Value | |
Before treatment | 14 | 10.8 ± 10.3 | N/A | N/A | 8 | 16.0 ± 10.8 | N/A | N/A |
Day 185/4 | 14 | 20.0 ± 15.8 | 9.2 | 0.003 | 8 | 31.3 ± 11.0 | 15.3 | 0.016 |
Day 307/5 | 14 | 23.8 ± 17.0 | 13.0 | <0.001 | 8 | 35.9 ± 11.6 | 19.9 | 0.008 |
Day 429/6 | 14 | 25.4 ± 18.6 | 14.6 | <0.001 | 8 | 37.9 ± 14.5 | 21.9 | 0.008 |
Day 551/7 | 11 | 29.6 ± 18.2 | 18.2 | 0.001 | 7 | 40.9 ± 12.0 | 25.7 | 0.016 |
Day 673/8 | 7 | 36.0 ± 16.3 | 22.5 | 0.016 | 6 | 40.5 ± 12.2 | 24.8 | 0.031 |
Day 795/9 | 7 | 36.4 ± 18.6 | 22.9 | 0.016 | 6 | 41.0 ± 15.5 | 25.3 | 0.031 |
Day 917/10 | 7 | 40.1 ± 18.6 | 26.6 | 0.016 | 6 | 45.3 ± 13.8 | 29.6 | 0.031 |
Day 1039/11 | 5 | 46.0 ± 15.1 | 31.6 | 0.062 | 5 | 46.0 ± 15.1 | 31.6 | 0.062 |
Day 1161/12 | 4 | 44.3 ± 13.5 | 35.8 | 0.125 | 4 | 44.3 ± 13.5 | 35.8 | 0.125 |
Day 1283/13 | 3 | 44.7 ± 15.9 | 37.4 | N/A | 3 | 44.7 ± 15.9 | 37.4 | N/A |
Day 1405/14 | 3 | 44.0 ± 15.1 | 36.7 | N/A | 3 | 44.0 ± 15.1 | 36.7 | N/A |
Day 1527/15 | 3 | 45.3 ± 13.9 | 38.0 | N/A | 3 | 45.3 ± 13.9 | 38.0 | N/A |
Time of Evaluation/Doses Already Received | N of Patients | HFMSE/X ± SD | Change from Baseline | p Value |
---|---|---|---|---|
Before treatment | 11 | 49.6 ± 7.9 | N/A | N/A |
Day 185/4 | 11 | 53.1 ± 7.7 | 3.5 | 0.008 |
Day 307/5 | 11 | 52.5 ± 9.7 | 2.9 | 0.084 |
Day 429/6 | 11 | 54.7 ± 9.0 | 5.1 | 0.049 |
Day 551/7 | 9 | 55.1 ± 9.2 | 6.1 | 0.008 |
Day 673/8 | 9 | 55.2 ± 9.5 | 6.2 | 0.020 |
Day 795/9 | 8 | 55.1 ± 7.9 | 6.5 | 0.023 |
Day 917/10 | 8 | 55.4 ± 8.2 | 6.8 | 0.016 |
Day 1039/11 | 6 | 55.8 ± 8.2 | 8.1 | 0.031 |
Day 1161/12 | 6 | 56.2 ± 8.3 | 8.5 | 0.031 |
Day 1283/13 | 2 | 59.0 ± 4.2 | 8.0 | N/A |
Time of Evaluation/Doses Already Received | N of Patients | RHS/X ± SD | Change from Baseline | p Value |
---|---|---|---|---|
Before treatment | 12 | 47.9 ± 16.1 | N/A | N/A |
Day 185/4 | 12 | 47.2 ± 15.8 | −0.7 | 0.313 |
Day 307/5 | 12 | 48.4 ± 15.9 | 0.5 | 0.578 |
Day 429/6 | 12 | 48.5 ± 16.2 | 0.6 | 0.577 |
Day 551/7 | 10 | 51.4 ± 17.1 | 1.5 | 0.250 |
Day 673/8 | 9 | 51.7 ± 18.5 | 2.0 | 0.055 |
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Belančić, A.; Strbad, T.; Kučan Štiglić, M.; Vitezić, D. Effectiveness of Nusinersen in Type 1, 2 and 3 Spinal Muscular Atrophy: Croatian Real-World Data. J. Clin. Med. 2023, 12, 2839. https://doi.org/10.3390/jcm12082839
Belančić A, Strbad T, Kučan Štiglić M, Vitezić D. Effectiveness of Nusinersen in Type 1, 2 and 3 Spinal Muscular Atrophy: Croatian Real-World Data. Journal of Clinical Medicine. 2023; 12(8):2839. https://doi.org/10.3390/jcm12082839
Chicago/Turabian StyleBelančić, Andrej, Tea Strbad, Marta Kučan Štiglić, and Dinko Vitezić. 2023. "Effectiveness of Nusinersen in Type 1, 2 and 3 Spinal Muscular Atrophy: Croatian Real-World Data" Journal of Clinical Medicine 12, no. 8: 2839. https://doi.org/10.3390/jcm12082839
APA StyleBelančić, A., Strbad, T., Kučan Štiglić, M., & Vitezić, D. (2023). Effectiveness of Nusinersen in Type 1, 2 and 3 Spinal Muscular Atrophy: Croatian Real-World Data. Journal of Clinical Medicine, 12(8), 2839. https://doi.org/10.3390/jcm12082839