Effect of nusinersen on respiratory function in paediatric spinal muscular atrophy types 1-3
© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ..
INTRODUCTION: Nusinersen is used in spinal muscular atrophy (SMA) to improve peripheral muscle function; however, respiratory effects are largely unknown.
AIM: To assess the effects of nusinersen on respiratory function in paediatric SMA during first year of treatment.
METHODS: A prospective observational study in paediatric patients with SMA who began receiving nusinersen in Queensland, Australia, from June 2018 to December 2019. Outcomes assessed were the age-appropriate respiratory investigations: spirometry, oscillometry, sniff nasal inspiratory pressure, mean inspiratory pressure, mean expiratory pressure, lung clearance index, as well as polysomnography (PSG) and muscle function testing. Lung function was collected retrospectively for up to 2 years prior to nusinersen initiation. Change in lung function was assessed using mixed effects linear regression models, while PSG and muscle function were compared using the Wilcoxon signed-rank test.
RESULTS: Twenty-eight patients (15 male, aged 0.08-18.58 years) were enrolled: type 1 (n=7); type 2 (n=12); type 3 (n=9). The annual rate of decline in FVC z-score prior to nusinersen initiation was -0.58 (95% CI -0.75 to -0.41), and post initiation was -0.25 (95% CI -0.46 to -0.03), with a significant difference in rate of decline (0.33 (95% CI 0.02 to 0.66) (p=0.04)). Most lung function measures were largely unchanged in the year post nusinersen initiation. The total Apnoea-Hypopnoea Index (AHI) was reduced from a median of 5.5 events/hour (IQR 2.1-10.1) at initiation to 2.7 events/hour (IQR 0.7-5.3) after 1 year (p=0.02). All SMA type 1% and 75% of SMA types 2 and 3 had pre-defined peripheral muscle response to nusinersen.
CONCLUSION: The first year of nusinersen treatment saw reduced lung function decline (especially in type 2) and improvement in AHI.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:77 |
|---|---|
| Enthalten in: |
Thorax - 77(2022), 1 vom: 11. Jan., Seite 40-46 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Chacko, Archana [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 02.02.2022 Date Revised 02.02.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1136/thoraxjnl-2020-216564 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM325148538 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM325148538 | ||
| 003 | DE-627 | ||
| 005 | 20231225191824.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1136/thoraxjnl-2020-216564 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1083.xml |
| 035 | |a (DE-627)NLM325148538 | ||
| 035 | |a (NLM)33963091 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chacko, Archana |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effect of nusinersen on respiratory function in paediatric spinal muscular atrophy types 1-3 |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.02.2022 | ||
| 500 | |a Date Revised 02.02.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a INTRODUCTION: Nusinersen is used in spinal muscular atrophy (SMA) to improve peripheral muscle function; however, respiratory effects are largely unknown | ||
| 520 | |a AIM: To assess the effects of nusinersen on respiratory function in paediatric SMA during first year of treatment | ||
| 520 | |a METHODS: A prospective observational study in paediatric patients with SMA who began receiving nusinersen in Queensland, Australia, from June 2018 to December 2019. Outcomes assessed were the age-appropriate respiratory investigations: spirometry, oscillometry, sniff nasal inspiratory pressure, mean inspiratory pressure, mean expiratory pressure, lung clearance index, as well as polysomnography (PSG) and muscle function testing. Lung function was collected retrospectively for up to 2 years prior to nusinersen initiation. Change in lung function was assessed using mixed effects linear regression models, while PSG and muscle function were compared using the Wilcoxon signed-rank test | ||
| 520 | |a RESULTS: Twenty-eight patients (15 male, aged 0.08-18.58 years) were enrolled: type 1 (n=7); type 2 (n=12); type 3 (n=9). The annual rate of decline in FVC z-score prior to nusinersen initiation was -0.58 (95% CI -0.75 to -0.41), and post initiation was -0.25 (95% CI -0.46 to -0.03), with a significant difference in rate of decline (0.33 (95% CI 0.02 to 0.66) (p=0.04)). Most lung function measures were largely unchanged in the year post nusinersen initiation. The total Apnoea-Hypopnoea Index (AHI) was reduced from a median of 5.5 events/hour (IQR 2.1-10.1) at initiation to 2.7 events/hour (IQR 0.7-5.3) after 1 year (p=0.02). All SMA type 1% and 75% of SMA types 2 and 3 had pre-defined peripheral muscle response to nusinersen | ||
| 520 | |a CONCLUSION: The first year of nusinersen treatment saw reduced lung function decline (especially in type 2) and improvement in AHI | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a paediatric lung disaese | |
| 650 | 4 | |a paediatric physician | |
| 650 | 4 | |a rare lung diseases | |
| 650 | 4 | |a respiratory measurement | |
| 650 | 4 | |a respiratory muscles | |
| 650 | 7 | |a Oligonucleotides |2 NLM | |
| 650 | 7 | |a nusinersen |2 NLM | |
| 650 | 7 | |a 5Z9SP3X666 |2 NLM | |
| 700 | 1 | |a Sly, Peter D |e verfasserin |4 aut | |
| 700 | 1 | |a Ware, Robert S |e verfasserin |4 aut | |
| 700 | 1 | |a Begum, Nelufa |e verfasserin |4 aut | |
| 700 | 1 | |a Deegan, Sean |e verfasserin |4 aut | |
| 700 | 1 | |a Thomas, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Gauld, Leanne M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Thorax |d 1946 |g 77(2022), 1 vom: 11. Jan., Seite 40-46 |w (DE-627)NLM00010387X |x 1468-3296 |7 nnns |
| 773 | 1 | 8 | |g volume:77 |g year:2022 |g number:1 |g day:11 |g month:01 |g pages:40-46 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1136/thoraxjnl-2020-216564 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 77 |j 2022 |e 1 |b 11 |c 01 |h 40-46 | ||