The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis

Diego Cadavid; Jeffrey A. Cohen; Mark S. Freedman; Myla D. Goldman; Hans Peter Hartung; Eva Havrdova; Douglas Jeffery; Raj Kapoor; Aaron Miller; Finn Sellebjerg; Deborah Kinch; Sophia Lee; Shulian Shang; Daniel Mikol

doi:10.1177/1352458516638941

The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis

Diego Cadavid^*, Jeffrey A. Cohen, Mark S. Freedman, Myla D. Goldman, Hans Peter Hartung, Eva Havrdova, Douglas Jeffery, Raj Kapoor, Aaron Miller, Finn Sellebjerg, Deborah Kinch, Sophia Lee, Shulian Shang, Daniel Mikol

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

35 Citationer (Scopus)

Abstract

Background: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function. Objective: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment. Methods: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm (n = 215) data, we analyzed disability progression using a novel progression endpoint, "EDSS-Plus," defined as progression on ≥1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ≥24 weeks apart and with a ≥20% minimum threshold change for T25FW and 9HPT. Results: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors' times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone. Conclusion: The 24-week confirmed minimum worsening of ≥20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression.

Originalsprog	Engelsk
Tidsskrift	Multiple Sclerosis
Vol/bind	23
Udgave nummer	1
Sider (fra-til)	94-105
Antal sider	12
ISSN	1352-4585
DOI	https://doi.org/10.1177/1352458516638941
Status	Udgivet - jan. 2017

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10.1177/1352458516638941

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Cadavid, D., Cohen, J. A., Freedman, M. S., Goldman, M. D., Hartung, H. P., Havrdova, E., Jeffery, D., Kapoor, R., Miller, A., Sellebjerg, F., Kinch, D., Lee, S., Shang, S., & Mikol, D. (2017). The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis. Multiple Sclerosis, 23(1), 94-105. https://doi.org/10.1177/1352458516638941

@article{eb4aba25549748bfa9e0437881821eec,

title = "The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis",

abstract = "Background: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function. Objective: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment. Methods: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm (n = 215) data, we analyzed disability progression using a novel progression endpoint, {"}EDSS-Plus,{"} defined as progression on ≥1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ≥24 weeks apart and with a ≥20% minimum threshold change for T25FW and 9HPT. Results: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors' times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone. Conclusion: The 24-week confirmed minimum worsening of ≥20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression.",

keywords = "Disability evaluation, disease progression, endpoint determination, secondary progressive multiple sclerosis",

author = "Diego Cadavid and Cohen, {Jeffrey A.} and Freedman, {Mark S.} and Goldman, {Myla D.} and Hartung, {Hans Peter} and Eva Havrdova and Douglas Jeffery and Raj Kapoor and Aaron Miller and Finn Sellebjerg and Deborah Kinch and Sophia Lee and Shulian Shang and Daniel Mikol",

year = "2017",

month = jan,

doi = "10.1177/1352458516638941",

language = "English",

volume = "23",

pages = "94--105",

journal = "Multiple Sclerosis Journal",

issn = "1352-4585",

publisher = "SAGE Publications",

number = "1",

}

TY - JOUR

T1 - The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis

AU - Cadavid, Diego

AU - Cohen, Jeffrey A.

AU - Freedman, Mark S.

AU - Goldman, Myla D.

AU - Hartung, Hans Peter

AU - Havrdova, Eva

AU - Jeffery, Douglas

AU - Kapoor, Raj

AU - Miller, Aaron

AU - Sellebjerg, Finn

AU - Kinch, Deborah

AU - Lee, Sophia

AU - Shang, Shulian

AU - Mikol, Daniel

PY - 2017/1

Y1 - 2017/1

N2 - Background: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function. Objective: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment. Methods: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm (n = 215) data, we analyzed disability progression using a novel progression endpoint, "EDSS-Plus," defined as progression on ≥1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ≥24 weeks apart and with a ≥20% minimum threshold change for T25FW and 9HPT. Results: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors' times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone. Conclusion: The 24-week confirmed minimum worsening of ≥20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression.

AB - Background: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function. Objective: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment. Methods: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm (n = 215) data, we analyzed disability progression using a novel progression endpoint, "EDSS-Plus," defined as progression on ≥1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ≥24 weeks apart and with a ≥20% minimum threshold change for T25FW and 9HPT. Results: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors' times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone. Conclusion: The 24-week confirmed minimum worsening of ≥20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression.

KW - Disability evaluation

KW - disease progression

KW - endpoint determination

KW - secondary progressive multiple sclerosis

U2 - 10.1177/1352458516638941

DO - 10.1177/1352458516638941

M3 - Journal article

C2 - 27003945

AN - SCOPUS:85011347312

SN - 1352-4585

VL - 23

SP - 94

EP - 105

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

IS - 1

ER -

The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis

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