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

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, Marina Anderson, Bridget Griffiths, Francesco Del Galdo, Hazem Youssef, Rajan Madhok, Barbara Arthurs, Maya Buch, Kim Fligelstone, Mohammed Zubair, Justin C. MasonChristopher P. Denton, Ariane L. Herrick (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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.

    Original languageEnglish
    Number of pages19
    JournalRheumatology
    Early online date13 Jan 2023
    DOIs
    Publication statusE-pub ahead of print - 13 Jan 2023

    Keywords

    • Systemic sclerosis
    • pain
    • disability
    • randomised controlled trial
    • corticosteroids

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