TY - JOUR
T1 - A Phase II randomised controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS)
AU - Griffiths-Jones, Deborah J.
AU - Garcia, Yvonne Sylvestre
AU - Ryder, W. David
AU - Pauling, John D.
AU - Hall, Frances
AU - Lanyon, Peter
AU - Bhat, Smita
AU - Douglas, Karen
AU - Gunawardena, Harsha
AU - Akil, Mohammed
AU - Anderson, Marina
AU - Griffiths, Bridget
AU - Del Galdo, Francesco
AU - Youssef, Hazem
AU - Madhok, Rajan
AU - Arthurs, Barbara
AU - Buch, Maya
AU - Fligelstone, Kim
AU - Zubair, Mohammed
AU - Mason, Justin C.
AU - Denton, Christopher P.
AU - Herrick, Ariane L.
N1 - Funding Information:
PRedSS was funded by Versus Arthritis. The study was supported by the United Kingdom Clinical Research Collaboration-registered King's Clinical Trials Unit at King's Health Partners, which is part funded by the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London and the NIHR Evaluation, Trials and Studies Coordinating Centre.
Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
PY - 2023/1/13
Y1 - 2023/1/13
N2 - Objectives: Although the painful and disabling features of early diffuse cutaneous systemic sclerosis (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate dose prednisolone in early dcSSc.Methods: PRedSS set out as a Phase II, multicentre, double-blind randomised controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomised to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Rodnan skin core (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients.Results: Thirty-five patients were randomised (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was -0.10 (97.5% CI -0.29-0.10), p= 0.254, and in mRSS -3.90 (97.5% CI -8.83-1.03), p= 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (p= 0.027), anxiety (p= 0.018) and helplessness (p= 0.040) than control patients at 3 months. There were no renal crises, but sample size was small.Conclusion: PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomised trial.Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718.
AB - Objectives: Although the painful and disabling features of early diffuse cutaneous systemic sclerosis (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate dose prednisolone in early dcSSc.Methods: PRedSS set out as a Phase II, multicentre, double-blind randomised controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomised to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Rodnan skin core (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients.Results: Thirty-five patients were randomised (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was -0.10 (97.5% CI -0.29-0.10), p= 0.254, and in mRSS -3.90 (97.5% CI -8.83-1.03), p= 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (p= 0.027), anxiety (p= 0.018) and helplessness (p= 0.040) than control patients at 3 months. There were no renal crises, but sample size was small.Conclusion: PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomised trial.Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718.
KW - Systemic sclerosis
KW - pain
KW - disability
KW - randomised controlled trial
KW - corticosteroids
U2 - 10.1093/rheumatology/kead012
DO - 10.1093/rheumatology/kead012
M3 - Article
C2 - 36637209
JO - Rheumatology
JF - Rheumatology
SN - 1462-0324
ER -