Changing respiratory expectations with the new disease trajectory of nusinersen treated spinal muscular atrophy [SMA] type 1

Fitzgerald, Dominic A.; Doumit, Michael; Abel, François

doi:10.1016/j.prrv.2018.07.002

Cited by 13 publications

(16 citation statements)

References 59 publications

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“…With the availability of these novel medications, there has been evolving change in the clinical phenotype of SMA compared to the natural history that even a new phenotype termed “treated SMA Type 1” is being proposed 5,44 . However, acknowledging that the response to these therapies can be varied due to multiple factors is important during clinical decision‐making and in family discussions.…”

Section: Long‐term Outcomesmentioning

confidence: 99%

“…Among infants with SMA, 60% have Type 1 disease, which is characterized by the onset of symptoms at 6 months of age or younger and a median life expectancy of less than 2 years without respiratory support 2,3 . There are phenotypic differences between the subtypes of SMA type 1, with Types 1A and 1B having worse impairment than subtype 1C 4–7 . In patients with neuromuscular weakness, the respiratory load exceeds the performance of the weakened muscles due to a combination of limited thoracic expansion, progressive stiffening of the rib cage, atelectasis and loss of lung volume, and worsening thoracic scoliosis with an asymmetric diaphragm and intercostal muscle activity 4,5 .…”

Section: Introductionmentioning

confidence: 99%

“…There are phenotypic differences between the subtypes of SMA type 1, with Types 1A and 1B having worse impairment than subtype 1C 4–7 . In patients with neuromuscular weakness, the respiratory load exceeds the performance of the weakened muscles due to a combination of limited thoracic expansion, progressive stiffening of the rib cage, atelectasis and loss of lung volume, and worsening thoracic scoliosis with an asymmetric diaphragm and intercostal muscle activity 4,5 . Reductions in the tidal volume are compensated by an increase in respiratory rate and therefore patients tend to breathe fast and shallow to maintain adequate minute ventilation, and this is predominant among those with SMA subtypes 1A and 1B compared to subtype 1C 8 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The respiratory impact of novel therapies for spinal muscular atrophy

Paul

Gushue

Kotha

et al. 2020

Pediatric Pulmonology

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The phenotype of spinal muscular atrophy (SMA) has been changing with the recent availability of three FDA‐approved treatments: intrathecal nusinersen, intravenous onasemnogene abeparvovec‐xioi, and enteral risdiplam. The degree of improvement in muscle strength and respiratory health varies with SMA genotype, severity of baseline neuromuscular and pulmonary impairment, medication used, and timing of the first dose. A spectrum of pulmonary outcomes has been reported with these novel medications when used early and in conjunction with proactive multidisciplinary management of comorbidities. In this review, we summarize the reported impact of these novel therapies on pulmonary well‐being and the improving trajectory of pulmonary morbidity, compared to the natural history of SMA. The importance of ongoing clinical monitoring albeit the improved phenotype is reiterated. We also discuss the limitations of the current SMA‐therapy trials and offer suggestions for future clinical‐outcome studies and long‐term monitoring.

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Section: Long‐term Outcomesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The respiratory impact of novel therapies for spinal muscular atrophy

Paul

Gushue

Kotha

et al. 2020

Pediatric Pulmonology

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“…Patients with SMA present with variable severity of chest wall distortion, paradoxical breathing and impaired airway clearance and cough, compounded by bulbar muscle weakness [5,6]. The assessment of respiratory function has gained interest in infants with SMA type 1 [7,8] as recently available treatments have improved patients' motor function and life expectancy [9][10][11]. In contrast, very few studies have focused on the long-term respiratory progression in SMA type 2 and 3 [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Respiratory Trajectories in Type 2 and 3 Spinal Muscular Atrophy in the iSMAC Cohort Study

Trucco¹,

Ridout

Scoto

et al. 2021

Neurology

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Objective.To describe the respiratory trajectories and their correlation with motor function in an international paediatric cohort of patients with type 2 and non-ambulant type 3 spinal muscular atrophy (SMA).Methods.Eight-year retrospective observational study of patients in the iSMAc natural history study. We retrieved anthropometrics, forced vital capacity (FVC) absolute, FVC% predicted (FVC%P.), Non-Invasive ventilation (NIV) requirement. Hammersmith functional motor scale (HFMS) and Revised performance of upper limb (RULM) were correlated with respiratory function. We excluded patients in interventional clinical trials and on Nusinersen commercial therapy.Results.There were 437 patients with SMA: 348 type 2, 89 non-ambulant type 3. Mean age at first visit was 6.9(±4.4) and 11.1(±4) years. In SMA type 2 FVC%P declined by 4.2%/year from 5 to 13 years, followed by a slower decline (1.0%/year). In type 3 FVC%P declined by 6.3%/year between 8 and 13 years, followed by a slower decline (0.9%/year). 39% SMA type 2 and 9% type 3 required NIV at median age 5.0(1.8-16.6) and 15.1(13.8-16.3) years. 84% SMA type 2 and 80% type 3 had scoliosis, 54% and 46% required surgery, which did not significantly affect respiratory decline. FVC%P positively correlated with HFMS and RULM in both subtypes.Conclusions.In SMA type 2 and non-ambulant type 3 lung function declines differently, with a common levelling after age 13 years. Lung and motor function correlated in both subtypes. Our data further defines the milder SMA phenotypes and provides novel information to benchmark the long-term efficacy of new treatments for SMA.

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“…Ein Medikament mit aktuell besonders hohem öffentlichem Interesse ist Nusinersen (Spinraza ® ) für die spinale Muskelatrophie beim Kind, welches Kosten von ca. 500.000 im ersten Therapiejahr und 250.000 in jedem weiteren Jahr verursacht [117,118]. Unter Therapie entwickeln sich die Kinder nach gegenwärtigem Kenntnisstand normal und sollten theoretisch auch eine normale Lebenserwartung haben.…”

Section: öGp-positionspapierunclassified

Masterplan 2025 der Österreichischen Gesellschaft für Pneumologie (ÖGP) – die erwartete Entwicklung und Versorgung respiratorischer Erkrankungen in Österreich

Studnicka

Baumgartner²,

Bolitschek

et al. 2020

Wien Klin Wochenschr

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Zusammenfassung Mitglieder der Österreichischen Gesellschaft für Pneumologie (ÖGP) beschreiben die erwartete Entwicklung der respiratorischen Gesundheit und zeigen Wege einer patientenorientierten und kosteneffizienten Versorgung für Österreich auf. Methoden: Im November 2017 trifft sich eine Gruppe von respiratorisch tätigen Ärzten, Pflegekräften und Physiotherapeuten, gemeinsam mit Vertretern von Selbsthilfe-Gruppen und Experten für Gesundheitsentwicklung, um die Themen Rahmenbedingungen für Lungengesundheit, Asthma und Allergie, COPD, Mukoviszidose und andere Krankheitsbilder der pädiatrischen Pneumologie, Infektionen in der Pneumologie, Schlafbezogene Atemstörungen, Interventionelle Pneumologie, Thorakale Onkologie, und Orphan Diseases zu bearbeiten. Ergebnisse: Respiratorische Erkrankungen sind extrem häufig und werden sehr oft durch individuelles Fehlverhalten (Zigarettenrauchen, Überernährung, körperliche Inaktivität) verursacht. Zudem wird für respiratorische Erkrankungen eine Zunahme der Prävalenz, aber eine Abnahme der Hospitalisierungen erwartet. Folgende Maßnahmen sind erforderlich, um den Herausforderungen der Zukunft zu begegnen. 1. Maßnahmen des Screenings und der Fallfindung sollen für Lungenkarzinom und COPD umgesetzt werden. 2. E-Health (Telemedizin, personalisierte Apps) soll vermehrt eingesetzt werden mit dem Ziel das Patientenmanagement zu erleichtern. 3. Regionale Unterschiede der medizinischen Versorgung können durch E‑Health und Harmonisierung der Angebote der Gesundheitskassen reduziert werden. 4. Patientenschulung und Awareness für respiratorische Erkrankungen soll verbessert werden (essentiell für Schlafstörungen, aber auch für andere respiratorische Erkrankungen) 5. Die angebotene Versorgung soll interprofessionell, und auf der Grundlage erkrankungsspezifischer Boards wie bei Tumorboards (z. B. für interstitielle Lungenerkrankungen, Schlaf und Allergie) erfolgen. 6. Die ambulante Rehabilitation im niedergelassenen Bereich kann einen großen Beitrag zur respiratorischen Gesundheit leisten. 7. Das vermehrte Verständnis der Molekularbiologie wird die personalisierte Medizin und zielgerichtete Therapien (z. B. für Asthma, Lungenkarzinom) ermöglichen, aber auch Gesundheitskosten verändern.

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Changing respiratory expectations with the new disease trajectory of nusinersen treated spinal muscular atrophy [SMA] type 1

Cited by 13 publications

References 59 publications

The respiratory impact of novel therapies for spinal muscular atrophy

The respiratory impact of novel therapies for spinal muscular atrophy

Respiratory Trajectories in Type 2 and 3 Spinal Muscular Atrophy in the iSMAC Cohort Study

Masterplan 2025 der Österreichischen Gesellschaft für Pneumologie (ÖGP) – die erwartete Entwicklung und Versorgung respiratorischer Erkrankungen in Österreich

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