Enrichment Strategy for Systemic Sclerosis Clinical Trials Targeting Skin Fibrosis: A Prospective, Multiethnic Cohort Study.
Journal
ACR open rheumatology
ISSN: 2578-5745
Titre abrégé: ACR Open Rheumatol
Pays: United States
ID NLM: 101740025
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
24
05
2020
accepted:
03
06
2020
pubmed:
29
7
2020
medline:
29
7
2020
entrez:
29
7
2020
Statut:
ppublish
Résumé
The modified Rodnan skin score (mRSS) is often used as a primary outcome measure in systemic sclerosis (SSc) randomized clinical trials (RCTs). Previous cohort studies with predominantly European Caucasian patients showed that setting an upper limit of mRSS as a selection criterion for RCTs leads effectively to enrichment with progressive patients. This study aimed to demonstrate this effect in an ethnically diverse cohort, rich in patients positive for anti-RNA polymerase III antibodies (Pol3). We selected from the Genetics versus Environment in Scleroderma Outcomes Study (GENISOS) cohort patients with diffuse cutaneous SSc (dcSSc), who had mRSS of 7 or more at inclusion and a documented mRSS after 12 ± 2 months. Progression of skin fibrosis was defined as an increase in mRSS greater than 5 points and 25% or more from baseline. To identify the optimal cutoff for the baseline mRSS yielding the highest sensitivity for progressive skin fibrosis, we developed ROC curves and logistic regression models with "progression" as the outcome variable and a binary variable of baseline mRSS cutoff point as predictor. We included 152 patients (age and disease duration [mean ± SD, years]: 48.7 ± 13.0 and 2.4 ± 1.5 respectively, 22.4% males, 34.2% Pol3-positive). Seventeen patients (11.2%) had skin fibrosis progression after 12 ± 2 months. An mRSS cutoff of 27 or less had the highest probability of progression (odds ratio, 9.12; 95% confidence interval: 1.173-70.851; P = 0.035; area under the curve, 0.652; sensitivity, 94%). We demonstrated in an ethnically diverse cohort of patients with early dcSSc and with a high proportion of patients who are Pol3-positive that setting an upper limit of the mRSS as a selection criterion leads effectively to cohort enrichment with progressors.
Identifiants
pubmed: 32720753
doi: 10.1002/acr2.11165
pmc: PMC7437132
doi:
Types de publication
Journal Article
Langues
eng
Pagination
496-502Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR003167
Pays : United States
Organisme : U.S. Department of Defense
ID : W81XWH-16-1-0296
Organisme : NIAMS NIH HHS
ID : R01 AR073284
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR003168
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01AR073284
Pays : United States
Informations de copyright
© 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
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