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

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.