RESUMEN
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 (â¼0.3 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.
RESUMEN
The COVID-19 pandemic is an unprecedented healthcare emergency causing mortality and illness across the world. Although primarily affecting the lungs, the SARS-CoV-2 virus also affects the cardiovascular system. In addition to cardiac effects, e.g. myocarditis, arrhythmias, and myocardial damage, the vasculature is affected in COVID-19, both directly by the SARS-CoV-2 virus, and indirectly as a result of a systemic inflammatory cytokine storm. This includes the role of the vascular endothelium in the recruitment of inflammatory leucocytes where they contribute to tissue damage and cytokine release, which are key drivers of acute respiratory distress syndrome (ARDS), in disseminated intravascular coagulation, and cardiovascular complications in COVID-19. There is also evidence linking endothelial cells (ECs) to SARS-CoV-2 infection including: (i) the expression and function of its receptor angiotensin-converting enzyme 2 (ACE2) in the vasculature; (ii) the prevalence of a Kawasaki disease-like syndrome (vasculitis) in COVID-19; and (iii) evidence of EC infection with SARS-CoV-2 in patients with fatal COVID-19. Here, the Working Group on Atherosclerosis and Vascular Biology together with the Council of Basic Cardiovascular Science of the European Society of Cardiology provide a Position Statement on the importance of the endothelium in the underlying pathophysiology behind the clinical presentation in COVID-19 and identify key questions for future research to address. We propose that endothelial biomarkers and tests of function (e.g. flow-mediated dilatation) should be evaluated for their usefulness in the risk stratification of COVID-19 patients. A better understanding of the effects of SARS-CoV-2 on endothelial biology in both the micro- and macrovasculature is required, and endothelial function testing should be considered in the follow-up of convalescent COVID-19 patients for early detection of long-term cardiovascular complications.