9-Hole Peg test
In the last years, Primary-Progressive Multiple Sclerosis (PPMS) is the focus of scientific interest of different studies concerning Multiple Sclerosis.
The Expanded Disability Status Scale (EDSS) remains the typical outcome measure in PPMS trials. However, it has been widely recognized as inadequate inability to identify predictors of disease progression in PPMS and is associated with several important weaknesses. These include very high inter- and intrarater variability and low risk for reaching one of the disability landmarks in the short term. In addition, EDSS landmarks primarily reflect mobility restrictions at the expense of other functional systems that could also contribute significantly to disability.
The authors report the results of an analysis of the PROMiSe data set undertaken to better understand the utility of the different measures of disability progression—EDSS, T25FW, and 9HPT alone and in combinations in patients with PPMS.
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| 9-Hole Peg test |
In the last years, Primary-Progressive Multiple Sclerosis (PPMS) is the focus of scientific interest of different studies concerning Multiple Sclerosis.
The Expanded Disability Status Scale (EDSS) remains the typical outcome measure in PPMS trials. However, it has been widely recognized as inadequate inability to identify predictors of disease progression in PPMS and is associated with several important weaknesses. These include very high inter- and intrarater variability and low risk for reaching one of the disability landmarks in the short term. In addition, EDSS landmarks primarily reflect mobility restrictions at the expense of other functional systems that could also contribute significantly to disability.
The authors report the results of an analysis of the PROMiSe data set undertaken to better understand the utility of the different measures of disability progression—EDSS, T25FW, and 9HPT alone and in combinations in patients with PPMS.
Comparative utility of disability progression measures in PPMS
Analysis of the PROMiSe data set
- Marcus W. Koch, MD, Ph.D.,
- Gary R. Cutter, Ph.D.,
- Gavin Giovannoni, MD, Ph.D.,
- Bernard M.J. Uitdehaag, MD, Ph.D.,
- Jerry S. Wolinsky, MD,
- Mat D. Davis, Ph.D.,
- Joshua R. Steinerman, MD and
- Volker Knappertz, MD
ABSTRACT
Objective: To assess the comparative utility of disability progression measures in primary progressive MS (PPMS) using the PROMiSe trial data set.
Methods: Data for patients randomized to placebo (n 5 316) in the PROMiSe trial were included in this analysis. Disability was assessed using change in single (Expanded Disability Status Scale [EDSS], timed 25-foot walk [T25FW], and 9-hole peg test [9HPT]) and composite disability measures (EDSS/T25FW, EDSS/9HPT, and EDSS/T25FW/9HPT). Cumulative and cross-sectional unconfirmed disability progression (UDP) and confirmed disability progression (CDP; sustained for 3 months) rates were assessed at 12 and 24 months.
Results: CDP rates defined by a ≥ 20% increase in T25FW were higher than those defined by EDSS score at 12 and 24 months. CDP rates defined by T25FW or EDSS score were higher than those defined by 9 HPT score. The 3-part composite measure was associated with more CDP events (41.4% and 63.9% of patients at 12 and 24 months, respectively) than the 2-part measure (EDSS/T25FW [38.5% and 59.5%, respectively]) and any single measure. Cumulative UDP and CDP rates were higher than cross-sectional rates.
Conclusions: The T25FW or composite measures of disability may be more sensitive to disability progression in patients with PPMS and should be considered as the primary endpoint for future studies of new therapies. CDP may be the preferred measure in classic randomized controlled trials in which cumulative disability progression rates are evaluated; UDP may be feasible for cross-sectional studies.
Objective: To assess the comparative utility of disability progression measures in primary progressive MS (PPMS) using the PROMiSe trial data set.
Methods: Data for patients randomized to placebo (n 5 316) in the PROMiSe trial were included in this analysis. Disability was assessed using change in single (Expanded Disability Status Scale [EDSS], timed 25-foot walk [T25FW], and 9-hole peg test [9HPT]) and composite disability measures (EDSS/T25FW, EDSS/9HPT, and EDSS/T25FW/9HPT). Cumulative and cross-sectional unconfirmed disability progression (UDP) and confirmed disability progression (CDP; sustained for 3 months) rates were assessed at 12 and 24 months.
Results: CDP rates defined by a ≥ 20% increase in T25FW were higher than those defined by EDSS score at 12 and 24 months. CDP rates defined by T25FW or EDSS score were higher than those defined by 9 HPT score. The 3-part composite measure was associated with more CDP events (41.4% and 63.9% of patients at 12 and 24 months, respectively) than the 2-part measure (EDSS/T25FW [38.5% and 59.5%, respectively]) and any single measure. Cumulative UDP and CDP rates were higher than cross-sectional rates.
Conclusions: The T25FW or composite measures of disability may be more sensitive to disability progression in patients with PPMS and should be considered as the primary endpoint for future studies of new therapies. CDP may be the preferred measure in classic randomized controlled trials in which cumulative disability progression rates are evaluated; UDP may be feasible for cross-sectional studies.
Results :
- T25FW 20% at 12 and 24 months was associated with higher rates of dis- ability progression than EDSS, and both T25FW 20% and EDSS were associated with higher disability rates than 9HPT 20%
- the normative approach to using CDP in classic randomized controlled trials is supported.
- combining specific disability measurements may be more useful in the clinical trial setting for assessing progression in patients with PPMS than single measures.
Comparison of cumulative and cross-sectional UDP and CDP rates for EDSS, T25FW 20%, and 9HPT 20%
(A) EDSS rates. (B) T25FW 20% rates. (C) 9HPT 20% rates. 3M CDP 5 3-month confirmed disability progression; 9HPT 5 9-hole peg test; EDSS 5 Expanded Disability Status Scale; T25FW 5 timed 25-foot walk; UDP 5 unconfirmed disability progression.
"Based on the observations presented here and those from previous studies, future studies of agents for the treatment of PPMS may benefit from either using T25FW 20% as a single outcome measure or using T25FW 20% in combination with the EDSS as a primary efficacy endpoint rather than EDSS alone, particularly if higher event rates over shorter exposure periods are sought "
ESPAÑOL
En los últimos años, la esclerosis múltiple primaria progresiva (PPMS) es el foco de interés científico de los diferentes estudios sobre la esclerosis múltiple.
La Escala Expandida de Estado de Discapacidad (EDSS) sigue siendo la medida de resultado, de mayor uso en los ensayos de PPMS. Sin embargo, se ha reconocido ampliamente que con dicha escala no es posible identificar adecuadamente los predictores de la progresión de la enfermedad en el PPMS y se asocia con varias debilidades importantes. Estos incluyen una variabilidad inter e intraobservador muy alta y bajo riesgo de alcanzar uno de los puntos de referencia de la discapacidad en el corto plazo. Además, los hitos de EDSS reflejan principalmente restricciones de movilidad a expensas de otros sistemas funcionales que también podrían contribuir significativamente a la discapacidad.
Los autores informan de los resultados de un análisis del conjunto de datos PROMiSe realizado para comprender mejor la utilidad de las diferentes medidas de progresión de la discapacidad: EDSS, T25FW y 9HPT solos y en combinaciones en pacientes con PPMS.
Utilidad comparada de las medidas de progresión de la discapacidad en PPMS Análisis del conjunto de datos PROMiSe
- Marcus W. Koch, MD, PhD,
- Gary R. Cutter, PhD,
- Gavin Giovannoni, MD, PhD,
- Bernard M.J. Uitdehaag, MD, PhD,
- Jerry S. Wolinsky, MD,
- Mat D. Davis, PhD,
- Joshua R. Steinerman, MD and
- Volker Knappertz, MD
Neurol Neuroimmunol Neuroinflamm May 2017 vol. 4 no. 4 e358
Objetivo: Evaluar la utilidad comparativa de las medidas de progresión de la discapacidad en la EM progresiva primaria (PPMS) utilizando el conjunto de datos del ensayo PROMiSe.
Métodos: Los datos de los pacientes asignados al azar a placebo (n 5 316) en el ensayo PROMiSe se incluyeron en este análisis. La discapacidad se evaluó mediante el cambio en la escala de estado de discapacidad expandida (EDSS), cronometrada de 25 pies (T25FW) y prueba de 9 agujeros (9HPT) y medidas compuestas de discapacidad (EDSS / T25FW, EDSS / 9HPT, Y EDSS / T25FW / 9HPT). Se evaluaron las tasas de progresión acumulada y transversal de la discapacidad no confirmada (UDP) y progresión confirmada de la discapacidad (CDP, sostenida durante 3 meses) a los 12 y 24 meses.
Resultados: Las tasas de CDP definidas por un aumento ≥ 20% en T25FW fueron superiores a las definidas por EDSS a los 12 y 24 meses. CDP tasas definidas por T25FW o EDSS puntuación fueron más altos que los definidos por 9HPT puntuación. La medida compuesta de 3 partes se asoció con más eventos CDP (41,4% y 63,9% de los pacientes a los 12 y 24 meses, respectivamente) que la medida en 2 partes (EDSS / T25FW [38,5% y 59,5%, respectivamente]) y cualquier medida única. Las tasas acumulativas de UDP y CDP fueron más altas que las tasas transversales.
Conclusiones: El T25FW o las medidas compuestas de la discapacidad pueden ser más sensibles a la progresión de la discapacidad en pacientes con PPMS y deben considerarse como el criterio principal de valoración para futuros estudios de nuevas terapias. CDP puede ser la medida preferida en los ensayos clínicos aleatorios clásicos en los que se evalúan las tasas de progresión acumulada de la discapacidad; UDP puede ser factible para estudios transversales.
Resultados:
- T25FW 20% a los 12 y 24 meses se asoció con mayores tasas de progresión de la discapacidad que EDSS, y tanto T25FW 20% y EDSS se asociaron con mayores índices de discapacidad que 9HPT 20%
- Se apoya el enfoque normativo para el uso de CDP en ensayos controlados aleatorios clásicos.
- La combinación de medidas específicas de discapacidad puede ser más útil en el ensayo clínico para evaluar la progresión en pacientes con PPMS que las medidas individuales.
"Sobre la base de las observaciones presentadas aquí y las de estudios previos, los estudios futuros de agentes para el tratamiento de PPMS pueden beneficiarse de T25FW 20% como medida de resultado individual o utilizando T25FW 20% en combinación con el EDSS como principal Eficacia en lugar de EDSS solo, en particular si se busca las tasas de eventos más altos durante períodos más cortos de exposición "
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