Category: Parkinsonism, Atypical: MSA
Objective: To study the rate of progression of multiple system atrophy (MSA) and assess for a potential ceiling effect of the Unified Multiple System Atrophy Rating Scale (UMSARS).
Background: Disease progression of MSA as measured by UMSARS varied significantly in natural history studies. Reported 1-year UMSARS-1 and UMSARS-2 progression rates ranged from 3.9 to 6.5 and 3.5 to 8.2 respectively. We hypothesize that this variability is due, at least in part, to differences in severity at enrollment and a potential ceiling effect in the scale, so that patients in more advanced stages may appear to worsen less, which would have important implications for clinical trial design.
Method: We analyzed the rate of change in the UMSARS in a large international cohort of well-characterized patients with a clinical diagnosis of possible or probable MSA enrolled in the Natural History Study of Synucleinopathies. Annualized progression rates were obtained using 2-year follow-up data.
Results: Three hundred and forty nine patients (61.4±7.9 years old) with MSA were enrolled. Disease duration was 4.5±5.1 years. 143 patients completed 1-year evaluations and 61 completed the 2-year evaluation. The 12-month progression rates were 5.4±5.1 for the UMSARS-I, 5.9±5.3 for the UMSARS-II, and 11.8±9.6 for the total score. The 24-month progression rates were 10.8±7.3 for the UMSARS-I, 12.2±7.9 for the UMSARS-II, and 22.6±13.7 for the total score.
Annualized progression rates were divided according to their baseline UMSARS-I and UMSARS II. There was a significant (p = 0.0153) inverse relationship between rate of progression and UMSARS-I at baseline. A similar, but not significant trend was observed with UMSARS-II at baseline.
Conclusion: The rate of progression as measured by UMSARS is influenced by the baseline disease severity. A possible ceiling effect should be considered when planning enrollment, power calculations, and outcome measures in clinical trials.
To cite this abstract in AMA style:
M. Pérez, J.A Palma, L. Norcliffe-Kaufmann, P. Millar Vernetti, W. Singer, P. Low, M.T Pellecchia, H.J Kim, C. Shibao, A. Peltier, I. Biaggioni, D. Giraldo, M.J Martí, A. Fanciulli, C. Terroba-Chambi, M. Merello, D. Goldstein, R. Freeman, C. Gibbons, S. Vernino, F. Krismer, G. Wenning, H. Kaufmann. Disease stage and UMSARS progression: Implications for clinical trials [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/disease-stage-and-umsars-progression-implications-for-clinical-trials/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/disease-stage-and-umsars-progression-implications-for-clinical-trials/