Respiratory function in 192 adult patients with spinal muscular atrophy (SMA) treated with nusinersen - a multicenter observational study

Claudia D Wurster^{1

2}, Benjamin Stolte³, Tobias Kessler^{4

5}, Maren Freigang⁶, Bogdan Bjelica⁷, Benjamin Ilse⁸, Jan C Koch⁹, Isabell Cordts¹⁰, Alexander Mensch¹¹, Daniel Zeller¹², Zeljko Uzelac¹³, Georges Sam⁴, Hanna Sophie Lapp⁶, Camilla Wohnrade⁷, Annekathrin Rödiger^{8

14}, Mohamad Tareq Muhandes⁹, Ilka Schneider^{11

15}, Julia Bellut¹², Julia Nentwich¹², Johannes Dorst^{13

16}, Joachim Schuster^{13

16}, Olivia Schreiber-Katz⁷, Alma Osmanovic^{7

17}, Andreas Totzeck³, Andreas Thimm³, Robert Steinbach⁸, Julian Grosskreutz^{8

18

19}, Christoph Kleinschnitz³, Albert C Ludolph^{13

16}, Marcus Deschauer¹⁰, Janbernd Kirschner²⁰, Jens Dreyhaupt²¹, Kurt Wollinsky²², Susanne Petri⁷, Markus Weiler⁴, Tim Hagenacker³, René Günther^{6

23}

Affiliations

¹ Institute of Human Genetics, Ulm University and Ulm University Medical Center, Albert-Einstein-Allee 11, 89081, Ulm, Germany. claudia.wurster@uni-ulm.de.
² Department of Neurology, Ulm University Medical Center, Ulm, Germany. claudia.wurster@uni-ulm.de.
³ Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, Essen, Germany.
⁴ Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
⁵ Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶ Department of Neurology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
⁷ Department of Neurology, Hannover Medical School, Hannover, Germany.
⁸ Department of Neurology, Jena University Hospital, Jena, Germany.
⁹ Department of Neurology, University Medicine Göttingen, Göttingen, Germany.
¹⁰ Department of Neurology, Klinikum rechts der Isar, School of Medicine and Health, Technical University of Munich, Munich, Germany.
¹¹ Department of Neurology, University Medicine Halle, Halle (Saale), Germany.
¹² Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
¹³ Department of Neurology, Ulm University Medical Center, Ulm, Germany.
¹⁴ Center for Rare Diseases, Jena University Hospital, Jena, Germany.
¹⁵ Department of Neurology, St. Georg Hospital Leipzig, Leipzig, Germany.
¹⁶ German Center for Neurodegenerative Diseases, DZNE, Site Ulm, Ulm, Germany.
¹⁷ Essen Centre for Rare Diseases (EZSE), University Hospital Essen, Essen, Germany.
¹⁸ Precision Neurology of Neuromuscular and Motor Neuron Diseases, University of Lübeck, Lübeck, Germany.
¹⁹ Cluster for Precision Medicine in Chronic Inflammation, Universities of Kiel and Lübeck, Lübeck, Germany.
²⁰ Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany.
²¹ Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
²² Department of Anesthesiology, RKU, Ulm University, Ulm, Germany.
²³ Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Dresden, Germany.

PMID: 40922023
PMCID: PMC12418672
DOI: 10.1186/s13023-025-04009-3

Respiratory function in 192 adult patients with spinal muscular atrophy (SMA) treated with nusinersen - a multicenter observational study

Claudia D Wurster et al. Orphanet J Rare Dis. 2025.

. 2025 Sep 8;20(1):476.

doi: 10.1186/s13023-025-04009-3.

Authors

Affiliations

¹ Institute of Human Genetics, Ulm University and Ulm University Medical Center, Albert-Einstein-Allee 11, 89081, Ulm, Germany. claudia.wurster@uni-ulm.de.
² Department of Neurology, Ulm University Medical Center, Ulm, Germany. claudia.wurster@uni-ulm.de.
³ Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, Essen, Germany.
⁴ Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
⁵ Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶ Department of Neurology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
⁷ Department of Neurology, Hannover Medical School, Hannover, Germany.
⁸ Department of Neurology, Jena University Hospital, Jena, Germany.
⁹ Department of Neurology, University Medicine Göttingen, Göttingen, Germany.
¹⁰ Department of Neurology, Klinikum rechts der Isar, School of Medicine and Health, Technical University of Munich, Munich, Germany.
¹¹ Department of Neurology, University Medicine Halle, Halle (Saale), Germany.
¹² Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
¹³ Department of Neurology, Ulm University Medical Center, Ulm, Germany.
¹⁴ Center for Rare Diseases, Jena University Hospital, Jena, Germany.
¹⁵ Department of Neurology, St. Georg Hospital Leipzig, Leipzig, Germany.
¹⁶ German Center for Neurodegenerative Diseases, DZNE, Site Ulm, Ulm, Germany.
¹⁷ Essen Centre for Rare Diseases (EZSE), University Hospital Essen, Essen, Germany.
¹⁸ Precision Neurology of Neuromuscular and Motor Neuron Diseases, University of Lübeck, Lübeck, Germany.
¹⁹ Cluster for Precision Medicine in Chronic Inflammation, Universities of Kiel and Lübeck, Lübeck, Germany.
²⁰ Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany.
²¹ Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
²² Department of Anesthesiology, RKU, Ulm University, Ulm, Germany.
²³ Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Dresden, Germany.

PMID: 40922023
PMCID: PMC12418672
DOI: 10.1186/s13023-025-04009-3

Abstract

Background: Natural history data show that respiratory function is impaired in SMA patients. Observational studies have shown stabilization of respiratory function in adult SMA patients treated with nusinersen. However, long-term studies investigating the effect of nusinersen on respiratory function in adult SMA patients are rare.

Methods: We examined respiratory function using forced vital capacity of predicted normal (FVC%), FVC in liters, capacity per second (FEV1) and peak expiratory flow (PEF) in 192 adult SMA patients treated with nusinersen for a median of 3.2 years (IQR: 2.1–4.0, range: 0.2–5.2). Changes in spirometric parameters were analyzed using individual linear regression models separate in each patient to estimate the slope. Additionally, three multivariable models were performed to assess the effect of age, sex, treatment duration, baseline FVC% and each one of the variables of interest (1) SMA type, (2) ambulation status, (3) spondylodesis on follow-up FVC%. Associations between respiratory parameters and motor function (HFMSE) were investigated via Scatter plots and Spearman’s rank correlation.

Results: Spirometric parameters remained stable during treatment (median annual rate of change of FVC% 0.17% (p = 0.40), FVC in liters -0.002 (p = 0.59), FEV1 -0.014 l (p = 0.06) and PEF 0.025 l/s (p = 0.65)). In all multivariable models, age, sex, treatment duration, SMA type, ambulation status, and spondylodesis showed no significant association with follow-up FVC%. No significant correlations were observed between respiratory and motor function.

Conclusion: Respiratory parameters remained stable during treatment with nusinersen in adult SMA patients over several years.

Clinical trial number: Not applicable.

Keywords: Adult patients; Forced vital capacity (FVC); Nusinersen; Respiratory function; Spinal muscular atrophy (SMA).

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was approved by the local ethics committees (approval number Dresden: EK 393122012, Essen: 18-8285-BO, Göttingen: 13/11/12, Halle: 2020 − 215 and 2021 − 101, Hannover: 6269, Heidelberg: S-554/2018, Jena: 3633-11/12, München: 16/14, Ulm 19/12, Würzburg: 165/18). Consent for publication: Not applicable. Competing interests: CDW has received honoraria from Biogen as an advisory board member and for lectures and as an advisory member and consultant from Hoffmann-La Roche. She also received travel expenses from Biogen. BS received advisory honoraria from Alexion and speaker honoraria and travel reimbursement from Biogen BB received compensation for travel expenses from ITF Pharma GmbH outside of the submitted work. JCK has received consultant fees from Biogen and Hoffmann-La Roche. IC has received research grants and speaker fees from Biogen and Hoffmann-La Roche, outside of the submitted work. AM received honoraria from Sanofi as an advisory board member and for lectures and as an advisory board member from Hormosan. DZ received compensation from Biogen for participation on advisory boards, from Novartis for consultancy work, and travel compensation from Angelini Pharma outside of the submitted work. ZU has received honoraria from Biogen as a consultant. HL has received consultant fees from Biogen. CW received travel compensations from ITF Pharma GmbH outside the submitted work. AR received speaker fees from Amylyx Pharmaceuticals and ROCHE and served on advisory boards for Biogen and Argenx outside of the submitted work. JDo has received honoraria from Biogen for lectures. AO has received honoraria from Biogen for lectures. ATo received speaker honoraria and travel reimbursement from Argenx. ATh received speaker honoraria and travel reimbursement from Biogen, Akcea Therapeutics, Swedish Orphan Biovitrum and Alnylam Pharmaceuticals. RS has received presentation fees from ITF Pharma outside of the submitted work. CK received speaker and consulting honoraria from Biogen, Roche and Novartis. ACL received financial research support from AB Science, Biogen Idec, Cytokinetics, GSK, Orion Pharam, Novartis, TauRx Therapeutics Ltd. and TEVA Pharmaceuticals. He also has received honoraria as a consultant from Mitsubishi, Orion Pharma, Novartis, Teva and as an advisory board member of Biogen, Treeway, and Hoffmann-La Roche. MD received honoraria as a speaker/consultant from Biogen and Roche. JK received compensation for clinical research and/or consultancy activities from Biogen, Novartis, Roche and ScholarRock. SP received speaker and consulting honoraria from Amylyx, Biogen, Roche, Ferrer, Italfarmaco, and Zambon. MW has received consultant honoraria from Biogen and Hoffmann-La Roche, and speaker honoraria and travel support for conference attendance from Biogen, all outside the present work. TH received speaker and consulting honoraria from Amylix, Biogen, Hoffmann-LaRoche, Sanofi-Genzyme, Alexion, Alnylam, UCB, Argenx and research support from Biogen and Hoffmann-LaRoche. RG has received personal fees from Biogen and Hoffmann-La Roche and served on advisory boards from Biogen, Hoffmann-La Roche, ITF Pharma, Zambon and research support from Biogen, outside of the submitted work. MF, JDr, JS, KW, TK, JB, JN, GS, MTM, JG, IS, OSK and BI report no competing interests.

Figures

**Fig. 1**
a: Boxplot FVC% of the entire SMA cohort. Boxplots of FVC% at T1 (baseline, start of treatment with nusinersen) to visit T19. Boxplots show the median and IQR, whiskers show the range. A dot plot was used for visit T19 due to the low number of observations. b: Boxplot FEV1 (l) of the entire SMA cohort. Boxplots of FEV1 (l) at T1 (baseline, start of treatment with nusinersen) to visit T19. Boxplots show the median and IQR, whiskers show the range. A dot plot was used for visit T19 due to the low number of observations. c: Boxplot PEF (l/s) of the entire SMA cohort. Boxplots of PEF (l/s) at T1 (baseline, start of treatment with nusinersen) to visit T19. Boxplots show the median and IQR, whiskers show the range. A dot plot was used for visit T19 due to the low number of observations

See this image and copyright information in PMC

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Respiratory function in 192 adult patients with spinal muscular atrophy (SMA) treated with nusinersen - a multicenter observational study

Affiliations

Respiratory function in 192 adult patients with spinal muscular atrophy (SMA) treated with nusinersen - a multicenter observational study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

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