Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 55-76 |
| Journal | Journal of Scleroderma and Related Disorders |
| Volume | 6 |
| Issue number | 1 |
| Early online date | 5 Oct 2020 |
| DOIs | |
| Publication status | Published - 1 Feb 2021 |
Bibliographical note
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)
Funding Information:
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.L.M. has received grant support US$10,000) from Actelion pharmaceuticals. J.D.P. has undertaken consultancy work for Actelion pharmaceuticals, Sojournix Pharma, and Boehringer Ingelheim. M.H. has received speaker honoraria (<US$10,000) from Actelion pharmaceuticals. C.P.D. has received personal fees from Actelion, Bayer, Boehringer Ingelheim, Corbus, Roche, Sanofi, CSL Behring, GlaxoSmithKline, and Inventiva. L.C. has served as an advisor and speaker, has received grant funding from Boehringer Ingelheim, and has served as an advisor for Mitsubishi Tanabe and Eicos Sciences, Inc. and on the data safety monitoring board for Reata. P.A.M. has received consulting fees from AbbVie, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, ChemoCentryx, CSL Behring, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Insmed, Jannsen, Kiniksa, Kyverna, Magenta, Novartis, Pfizer, Sparrow, Takeda, and Talaris; has received research support from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, ChemoCentryx, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, and InflaRx; and has received royalties from UpToDate. Y.A. has received personal fees from Actelion, Bayer, Boehringer Ingelheim, Curzion, Roche, Sanofi, and Inventiva. M.H.B. has received meeting support from Boehringer Ingelheim. D.C. has received research funding from Pfizer, Novartis, BMS, AstraZeneca, Abbvie, Lilly, Astellas, Merck/EMD Serono, and Bayer and has received consulting fees from Pfizer, Novartis, BMS, Abbvie, Asahi Kasei, PledPharma, Ipsen, and Astellas. V.S. is a consultant to Boehringer Ingelheim, CSL Behring, Corbus, Galapagos, Forbius, and Eicos. F.D.G. has received research funding and/or consulting fees or other remuneration from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Actelion, Capella Bioscience, Chemomab, Kymab, Actelion, iqvia, and Mitsubishi Tanabe. A.L., D.R., R.S., F.Z., R.W., W.T., D.G., and S.F. have no conflict of interest.
Publisher Copyright:
© The Author(s) 2020.
Funding
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.L.M. has received grant support US$10,000) from Actelion pharmaceuticals. J.D.P. has undertaken consultancy work for Actelion pharmaceuticals, Sojournix Pharma, and Boehringer Ingelheim. M.H. has received speaker honoraria (<US$10,000) from Actelion pharmaceuticals. C.P.D. has received personal fees from Actelion, Bayer, Boehringer Ingelheim, Corbus, Roche, Sanofi, CSL Behring, GlaxoSmithKline, and Inventiva. L.C. has served as an advisor and speaker, has received grant funding from Boehringer Ingelheim, and has served as an advisor for Mitsubishi Tanabe and Eicos Sciences, Inc. and on the data safety monitoring board for Reata. P.A.M. has received consulting fees from AbbVie, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, ChemoCentryx, CSL Behring, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Insmed, Jannsen, Kiniksa, Kyverna, Magenta, Novartis, Pfizer, Sparrow, Takeda, and Talaris; has received research support from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, ChemoCentryx, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, and InflaRx; and has received royalties from UpToDate. Y.A. has received personal fees from Actelion, Bayer, Boehringer Ingelheim, Curzion, Roche, Sanofi, and Inventiva. M.H.B. has received meeting support from Boehringer Ingelheim. D.C. has received research funding from Pfizer, Novartis, BMS, AstraZeneca, Abbvie, Lilly, Astellas, Merck/EMD Serono, and Bayer and has received consulting fees from Pfizer, Novartis, BMS, Abbvie, Asahi Kasei, PledPharma, Ipsen, and Astellas. V.S. is a consultant to Boehringer Ingelheim, CSL Behring, Corbus, Galapagos, Forbius, and Eicos. F.D.G. has received research funding and/or consulting fees or other remuneration from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Actelion, Capella Bioscience, Chemomab, Kymab, Actelion, iqvia, and Mitsubishi Tanabe. A.L., D.R., R.S., F.Z., R.W., W.T., D.G., and S.F. have no conflict of interest. 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)
Keywords
- classifications
- combined response index
- composite score
- limited cutaneous systemic sclerosis
- quality of life
- scleroderma
- Systemic sclerosis
ASJC Scopus subject areas
- Immunology and Allergy
- Rheumatology
- Immunology