Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I
Abstract
:1. Introduction
2. Materials and Methods
3. Results
- ✓
- Higher improvements in CHOP-INTEND scores 6 months after T1 compared to the same period after T2. Calculated medians for CHOP-INTEND: before T1—15 points, 6 months later it increased to 35 points; before T2—40 points, 6 months later it increased to 52 points.
- ✓
- Ventilation hours were not modified 6 months after T1, the median being 16 for both evaluations. However, before T2, median for the ventilation hours dropped to 12 and after T2 to 8 h/day.
- ✓
- Median for cough assist number of sessions was 4 before T1, 3 after 6 months from T1. Before T2, median was 3, and 6 months later it decreased to 1 time per day.
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient | 1NZ | 2NZ | 3NZ | 4NZ | 5NZ | 6ZN | 7NZ |
---|---|---|---|---|---|---|---|
Gender | M | M | F | M | M | F | F |
Age at symptom onset (months) | 1 | 1 | 4.5 | 4.5 | 2 | 2 | 0.5 |
Age at T1 (months) | 2 | 2 | 6 | 6 | 3 | 5 | 3.5 |
Side effects after T1 | no side effects | no side effects | no side effects | no side effects | no side effects | liver enzymes slightly increased; inappetence | no side effects |
Age at T2 (months) | 9.5 | 12 | 12 | 12 | 14 | 23 | 19 |
Side effects after T2 | AST, ALT higher 2.5-fold from normal; fever | AST, ALT slightly higher; fever; vomit | AST, ALT slightly higher; vomit | AST, ALT slightly higher | AST, ALT higher 3.5-fold from normal; fever | no side effects | severe platelet level drop; AST, ALT higher 10-fold from normal; fever; vomit; bleeding; anemia; respiratory arrest; renal failure |
Duration of steroid (months) | 3 | 2 | 2 | 2 | 5 | 2 | 2.5 |
Ventilation hours before T1 | 16 | 16 | 16 | 0 | 16 | 14 | 16 |
Ventilation hours 6 months after T1 | 16 | 12 | 16 | 0 | 16 | 12 | 16 |
Ventilation hours before T2 | 14 | 12 | 12 | 0 | 12 | 8 | 16 |
Ventilation hours 6 months after T2 | 8 | 4 | 10 | 0 | 8 | 8 | 24 |
Number of cough assist sessions before T1 | 6 | 4 | 6 | 3 | 4 | 4 | 6 |
Number of cough assist sessions 6 months after T1 | 6 | 3 | 4 | 2 | 3 | 3 | 4 |
Number of cough assist sessions before T2 | 4 | 3 | 3 | 2 | 2 | 2 | 3 |
Number of cough assist sessions 6 months after T2 | 2 | 1 | 2 | 1 | 1 | 2 | 0 |
CHOP before T1 | 9 | 14 | 15 | 36 | 22 | 29 | 8 |
CHOP 6 months after T1 | 25 | 43 | 35 | 46 | 34 | 33 | 29 |
CHOP before T2 | 40 | 51 | 40 | 47 | 36 | 38 | 36 |
CHOP 6 months after T2 | 51 | 60 | 44 | 54 | 52 | 47 | 0 |
Patient | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 |
---|---|---|---|---|---|---|
Gender | M | F | M | M | F | F |
Age at symptom onset (months) | 0.5 | 1.5 | 5 | 3 | 2 | 0.5 |
Age at T1 (months) | 2 | 2 | 6 | 5 | 3 | 2 |
Side effects after T1 | no side effects | no side effects | mild agitation | mild agitation | no side effects | no side effects |
Age at first current study evaluation (months) | 14 | 14 | 18 | 16 | 12 | 10 |
Ventilation hours at first current study evaluation | 12 | 10 | 8 | 10 | 12 | 12 |
Ventilation hours at second current study evaluation (6 months later) | 10 | 8 | 6 | 8 | 11 | 12 |
Number of cough assist sessions at first current study evaluation | 4 | 3 | 3 | 4 | 5 | 2 |
Number of cough assist sessions at second current study evaluation (6 months later) | 3 | 3 | 3 | 4 | 4 | 2 |
CHOP at first current study evaluation | 44 | 50 | 34 | 38 | 42 | 54 |
CHOP at second current study evaluation (6 months later) | 54 | 62 | 39 | 44 | 48 | 64 |
CHOP Evolution | CHOP Evolution in Control Group after 6 Months | CHOP Evolution in Study Group at 6 Months after T1 | CHOP Evolution in Study Group at 6 Months after T2 | |
---|---|---|---|---|
N | Valid | 6 | 6 | 6 |
Missing | 0 | 0 | 0 | |
Mean | 13.33 | 15.17 | 9.33 | |
Median | 13.00 | 14.00 | 9.00 | |
Minimum | 8 | 4.00 | 4.00 | |
Maximum | 20 | 29.00 | 16.00 |
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Mirea, A.; Shelby, E.-S.; Axente, M.; Badina, M.; Padure, L.; Leanca, M.; Dima, V.; Sporea, C. Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I. J. Clin. Med. 2021, 10, 5540. https://doi.org/10.3390/jcm10235540
Mirea A, Shelby E-S, Axente M, Badina M, Padure L, Leanca M, Dima V, Sporea C. Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I. Journal of Clinical Medicine. 2021; 10(23):5540. https://doi.org/10.3390/jcm10235540
Chicago/Turabian StyleMirea, Andrada, Elena-Silvia Shelby, Mihaela Axente, Mihaela Badina, Liliana Padure, Madalina Leanca, Vlad Dima, and Corina Sporea. 2021. "Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I" Journal of Clinical Medicine 10, no. 23: 5540. https://doi.org/10.3390/jcm10235540