TY - JOUR
T1 - Considerations for a combined index for limited cutaneous systemic sclerosis to support drug development and improve outcomes
AU - Lescoat, Alain
AU - Murphy, Susan L.
AU - Roofeh, David
AU - Pauling, John D.
AU - Hughes, Michael
AU - Sandler, Robert
AU - Zimmermann, François
AU - Wessel, Rachel
AU - Townsend, Whitney
AU - Chung, Lorinda
AU - Denton, Christopher P.
AU - Merkel, Peter A.
AU - Steen, Virginia
AU - Allanore, Yannick
AU - Del Galdo, Francesco
AU - Godard, Dominique
AU - Cella, David
AU - Farrington, Sue
AU - Buch, Maya H.
AU - Khanna, Dinesh
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The project was funded by a grant by SRUK/WSF (UH&UHR1). Dr Khanna was supported by NIH/NIAMS K24 (AR063120). Dr. Roofeh was funded by the NIH/NIAMS T32 grant (AR007080)
Publisher Copyright:
© The Author(s) 2020.
PY - 2020
Y1 - 2020
N2 - Systemic sclerosis (systemic scleroderma) is characterized by a heterogeneous range of clinical manifestations. Systemic sclerosis is classified into limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis subgroups based on the extent of skin involvement. Randomized controlled trials in scleroderma have mainly focused on diffuse cutaneous systemic sclerosis partly because the measurement of skin involvement, critical for evaluating a therapeutic intervention, is more dynamic in this subset. Nonetheless, limited cutaneous systemic sclerosis, the most common cutaneous subset (about two-third), is also associated with significant morbidity and detrimental impact on health-related quality of life. The lack of interventional studies in limited cutaneous systemic sclerosis is partly due to a lack of relevant outcome measures to evaluate this subgroup. Combining several clinically meaningful outcomes selected specifically for limited cutaneous systemic sclerosis may improve representativeness in clinical trials and responsiveness of outcomes measured in randomized controlled trials. A composite index dedicated to limited cutaneous systemic sclerosis combining such relevant outcomes could advance clinical trial development for limited cutaneous systemic sclerosis by providing the opportunity to test and select among candidate drugs that could act as disease-modifying treatments for this neglected subgroup of systemic sclerosis. This proposed index would include items selected by expert physicians and patients with limited cutaneous systemic sclerosis across domains grounded in the lived experience of limited cutaneous systemic sclerosis. This article reviews the reasons behind the relative neglect of limited cutaneous systemic sclerosis, discusses the current state of outcome measures for limited cutaneous systemic sclerosis, identifies challenges, and proposes a roadmap for a combined limited cutaneous systemic sclerosis-specific treatment response index.
AB - Systemic sclerosis (systemic scleroderma) is characterized by a heterogeneous range of clinical manifestations. Systemic sclerosis is classified into limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis subgroups based on the extent of skin involvement. Randomized controlled trials in scleroderma have mainly focused on diffuse cutaneous systemic sclerosis partly because the measurement of skin involvement, critical for evaluating a therapeutic intervention, is more dynamic in this subset. Nonetheless, limited cutaneous systemic sclerosis, the most common cutaneous subset (about two-third), is also associated with significant morbidity and detrimental impact on health-related quality of life. The lack of interventional studies in limited cutaneous systemic sclerosis is partly due to a lack of relevant outcome measures to evaluate this subgroup. Combining several clinically meaningful outcomes selected specifically for limited cutaneous systemic sclerosis may improve representativeness in clinical trials and responsiveness of outcomes measured in randomized controlled trials. A composite index dedicated to limited cutaneous systemic sclerosis combining such relevant outcomes could advance clinical trial development for limited cutaneous systemic sclerosis by providing the opportunity to test and select among candidate drugs that could act as disease-modifying treatments for this neglected subgroup of systemic sclerosis. This proposed index would include items selected by expert physicians and patients with limited cutaneous systemic sclerosis across domains grounded in the lived experience of limited cutaneous systemic sclerosis. This article reviews the reasons behind the relative neglect of limited cutaneous systemic sclerosis, discusses the current state of outcome measures for limited cutaneous systemic sclerosis, identifies challenges, and proposes a roadmap for a combined limited cutaneous systemic sclerosis-specific treatment response index.
KW - Systemic sclerosis
KW - classifications
KW - combined response index
KW - composite score
KW - limited cutaneous systemic sclerosis
KW - quality of life
KW - scleroderma
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U2 - 10.1177/2397198320961967
DO - 10.1177/2397198320961967
M3 - Review article
C2 - 34316516
AN - SCOPUS:85092137488
JO - Journal of Scleroderma and Related Disorders
JF - Journal of Scleroderma and Related Disorders
SN - 2397-1983
ER -