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A Phase II randomized controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS)

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  • Deborah J Griffiths-Jones
  • Yvonne Sylvestre Garcia
  • W David Ryder
  • John D Pauling
  • Frances Hall
  • Peter Lanyon
  • Smita Bhat
  • Karen Douglas
  • Harsha Gunawardena
  • Mohammed Akil
  • Bridget Griffiths
  • Francesco Del Galdo
  • Hazem Youssef
  • Rajan Madhok
  • Barbara Arthurs
  • Maya Buch
  • Kim Fligelstone
  • Mohammed Zubair
  • Justin C Mason
  • Christopher P Denton
  • Ariane L Herrick
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<mark>Journal publication date</mark>30/09/2023
<mark>Journal</mark>Rheumatology
Issue number9
Volume62
Number of pages6
Pages (from-to)3133-3138
Publication StatusPublished
Early online date13/01/23
<mark>Original language</mark>English

Abstract

Objectives Although the painful and disabling features of early diffuse cutaneous SSc (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 randomized controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomized 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 HAQ Disability Index (HAQ-DI) and modified Rodnan skin score (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 randomized (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 randomized trial. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718.