Abstract
Background: Raynaud's phenomenon (RP) and digital ulcers (DU) are important features of digital vasculopathy in systemic sclerosis (SSc). Laser Doppler flowmetry (LDF), Laser Doppler Imaging (LDI) and Laser Speckle Contrast Imaging (LSCI) can non-invasively quantify digital perfusion and may be useful outcome measures for SSc-RP and/or SSc-DU clinical trials. We undertook a systematic literature review to evaluate the performance of laser-derived imaging as outcome measures in clinical trials of SSc-related digital vasculopathy. Methods: Standardized searches (EMBASE and MEDLINE) identified trials that incorporated laser-derived imaging of digital vasculopathy in adult subjects with SSc. Data was extracted (by >2 reviewers) on study design, laser endpoints, and reported outcomes. Study quality was assessed using validated instruments (PROSPERO 2019:CRD42019142409). Results: Of 126 identified articles, full data extraction was undertaken from 29 studies. Fifteen randomized and 14 non-randomized trials (total of 689 SSc patients with mean 23.8/study) have evaluated a broad range of oral, intravenous and topical interventions for SSc-RP (n = 11), digital perfusion alone (n = 15) and SSc-DU (n = 3). The studies were published between 1987 and 2019 (17/29 since 2010) and incorporated LDF (11/29), LDI (15/29) and LSCI (4/29, including one with LDF); with LSCI and LDI more commonly incorporated in recent trials. Most studies (16/29, 55%) reported improvement in digital perfusion following intervention, often concordant with patient- and clinician-derived outcomes. Conclusions: Establishing laser-derived methods as a surrogate for SSc-related digital vasculopathy will greatly support drug development. Full-field perfusion of the digits (with/without provocation testing) is a promising clinical trial outcome measure for trials of SSc-related digital vasculopathy.
| Original language | English |
|---|---|
| Pages (from-to) | 1114-1130 |
| Number of pages | 17 |
| Journal | Seminars in Arthritis and Rheumatism |
| Volume | 50 |
| Issue number | 5 |
| Early online date | 6 Jul 2020 |
| DOIs | |
| Publication status | Published - 31 Oct 2020 |
Funding
John Pauling has received research grants, honoraria and undertaken consultancy work for Actelion pharmaceuticals. John Pauling has undertaken consultancy work for Boehringher-Ingelheim and Sojournix Pharma. Andrea Guida and Natalia Hackett have no relevant disclosures. Dr. Merkel has received research support from AstraZeneca, Boeringher-Ingelheim, Bristol-Myers Squibb, Celgene, ChemoCentryx, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Kypha, and TerumoBCT. Dr. Merkel has received payment for consulting form AbbVie, AstraZeneca, Biogen, Boeringher-Ingelheim, Bristol-Myers Squibb, Celgene, ChemoCentryx, CSL Behring, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Insmed, Jannsen, Kiniksa, Pfizer, Sparrow, and Talaris. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Ms Natalia Hackett supported this work as part of a University of Bristol Medical School 3rd year Student Selected Components (SSC) placement. Dr Andrea Guida supported this work as part of an ERASMUS+ placement.
Keywords
- Clinical trials
- Laser doppler
- Laser speckle contrast imaging
- Raynaud's phenomenon
- Systemic sclerosis
- Vasculopathy
ASJC Scopus subject areas
- Rheumatology
- Anesthesiology and Pain Medicine