Observational studyRheumatology (Oxford, England)2021
Defining the optimal disease duration of early diffuse systemic sclerosis for clinical trial design.
Observational study in Rheumatology (Oxford, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Efficacy of cyclophosphamide for skin fibrosis in systemic sclerosis: a systematic review and single-arm meta-analysis.European journal of clinical pharmacology · 2025Pooled it
- Skin Biopsies Enhance Prediction of Clinical Trajectory in Diffuse Cutaneous Systemic Sclerosis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Systemic sclerosis: pathogenic mechanisms and their implications for treatment.Seminars in immunopathology · 2025Review
- Hand Swelling and Other Non-Raynaud Phenomenon Symptoms as the Initial Presentation of Systemic Sclerosis: Prevalence and Clinical Associations in Two US Cohorts.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Re-envisioning clinical trial design in systemic sclerosis.Expert review of clinical immunology · 2025Review
- Abnormal Esophageal Scintigraphy Associates With a Distinct Clinical Phenotype in Patients With Systemic Sclerosis.ACR open rheumatology · 2025Article
- Predictors of clinical features in early-onset severe systemic sclerosis: An analysis from a multicenter prospective observational Japanese cohort.The Journal of dermatology · 2024Observational
- Back to the future: targeting the extracellular matrix to treat systemic sclerosis.Nature reviews. Rheumatology · 2023Review
- A data-driven approach finds RNA polymerase III antibody and tendon friction rubs as enrichment tools for early diffuse scleroderma trials.Rheumatology (Oxford, England) · 2023Article
- Very Early Diagnosis of Systemic Sclerosis: Deciphering the heterogeneity of systemic sclerosis in the very early stages of the disease.Journal of scleroderma and related disorders · 2023Article
- Anemia Is an Indicator for Worse Organ Damage Trajectories in Patients with Systemic Sclerosis: A Retrospective Study.Journal of clinical medicine · 2022Article
- Skin involvement in early diffuse cutaneous systemic sclerosis: an unmet clinical need.Nature reviews. Rheumatology · 2022Review
- Large-scale analysis of longitudinal skin gene expression in systemic sclerosis reveals relationships of immune cell and fibroblast activity with skin thickness and a trend towards normalisation over time.Annals of the rheumatic diseases · 2022Article
- Clinical characteristics, visceral involvement, and mortality in at-risk or early diffuse systemic sclerosis: a longitudinal analysis of an observational prospective multicenter US cohort.Arthritis research & therapy · 2021Observational
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesClinical trials in early diffuse cutaneous systemic sclerosis (SSc) using the modified Rodnan skin score (mRSS) as the primary outcome measure have most often been negative. We wanted to assess how the definition of disease onset (first SSc manifestation vs first non-Raynaud manifestation) and varying lengths of disease duration at trial entry as an inclusion criteria functioned. Our objective was to optimize trial inclusion criteria.
methodsWe used the prospective, observational University of Pittsburgh Scleroderma Cohort to identify early diffuse SSc patients first evaluated between 1980 and 2015. All had <3 years from first SSc (n = 481) or first non-Raynaud manifestation (n = 514) and three or more mRSS scores. We used descriptive, survival and group-based trajectory analyses to compare the different definitions of disease onset and disease duration as inclusion criteria for clinical trials.
resultsThere was no appreciable difference between using first SSc manifestation compared with first non-Raynaud manifestation as the definition of disease onset. Compared with other disease durations, <18 months of disease had >70% of patients fitting into trajectories with worsening cutaneous disease over 6 months of follow-up. Longer disease durations demonstrated the majority of patients with trajectories showing an improvement in mRSS (regression to the mean) over 6 months.
conclusionsRegardless of whether the first SSc or first non-Raynaud manifestation is used to define disease onset, duration of <18 months at enrolment is preferable. A longer disease duration criterion more frequently results in regression to the mean of the mRSS score, and likely contributes to negative trial outcomes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.