Disease Progression in Multiple System Atrophy—Novel Modeling Framework and Predictive Factors

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  • the EMSA-SG Natural History Study Investigators

Background: Multiple system atrophy (MSA) is a rare and aggressive neurodegenerative disease that typically leads to death 6 to 10 years after symptom onset. The rapid evolution renders it crucial to understand the general disease progression and factors affecting the disease course. Objectives: The aims of this study were to develop a novel disease-progression model to estimate a population-level MSA progression trajectory and predict patient-specific continuous disease stages describing the degree of progress into the disease. Methods: The disease-progression model estimated a population-level progression trajectory of subscales of the Unified MSA Rating Scale and the Unified Parkinson's Disease Rating Scale using patients in the European MSA natural history study. The predicted disease continuum was validated via multiple analyses based on reported anchor points, and the effect of MSA subtype on the rate of disease progression was evaluated. Results: The predicted disease continuum spanned approximately 6 years, with an estimated average duration of 51 months for a patient with global disability score 0 to reach the highest level of 4. The predicted continuous disease stages were shown to be correlated with time of symptom onset and predictive of survival time. MSA motor subtype was found to significantly affect disease progression, with MSA-parkinsonian (MSA-P) type patients having an accelerated rate of progression. Conclusions: The proposed modeling framework introduces a new method of analyzing and interpreting the progression of MSA. It can provide new insights and opportunities for investigating covariate effects on the rate of progression and provide well-founded predictions of patient-level future progressions.

OriginalsprogEngelsk
TidsskriftMovement Disorders
Vol/bind37
Udgave nummer8
Sider (fra-til)1719-1727
ISSN0885-3185
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
K.S. reports personal fees from Teva, UCB, Lundbeck, AOP Orphan Pharmaceuticals AG, Roche, Grünenthal, and AbbVie; honoraria from the International Parkinson and Movement Disorders Society; and research grants from the FWF Austrian Science Fund, The Michael J. Fox Foundation, and the International Parkinson and Movement Disorder Society outside of the submitted work.

Funding Information:
F.K. reports personal fees from Institut de Recherches Internationales Servier, Clarion Healthcare, and the Austrian Society of Neurology and grant support from the MSA Coalition outside of the submitted work.

Funding Information:
G.K.W. reports royalties from the Springer Nature Publishing Group and Thieme Verlag; speaker fees and honoraria from the International Parkinson Disease and Movement Disorders Society, the Austrian Parkinson Society, the Austrian Autonomic Society, Eisai, Inhibikase, Lundbeck, Minoryx, Novartis, Ono Pharma, Takeda, Theravance Biopharma, and Vaxxinity; and research grants from the Stichting ParkinsonFond, US MSA Coalition, Dr Johannes Tuba Stiftung, and the Austrian Science Fund.

Funding Information:
W.P. reports personal fees from AbbVie, AFFiRiS, AstraZeneca, Bial, Boston Scientific, Britannia, Intec, Ipsen, Lundbeck, NeuroDerm, Neurocrine, Denali Pharmaceuticals, Novartis, Orion Pharma, Prexton, Teva, UCB, and Zambon; royalties from Thieme, Wiley Blackwell, Oxford University Press, and Cambridge University Press; and grant support from The Michael J. Fox Foundation, EU FP7, and Horizon 2020.

Funding Information:
This work was partly funded by Innovation Fund Denmark (9066‐00005B). The EMSA Natural History Study was supported by funds of the Fifth Framework Programme of the European Community (QLK6‐CT‐2000‐00661). Funding agencies

Publisher Copyright:
© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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