POS0850 A PHASE II RANDOMISED CONTROLLED TRIAL OF ORAL PREDNISOLONE IN EARLY DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS (PRedSS)

Background A highly controversial question is whether or not corticosteroids should be prescribed for patients with early diffuse cutaneous systemic sclerosis (dcSSc). Although the painful and disabling features of dcSSc (including tight itchy skin, contractures, fatigue) have an inflammatory basis are likely to respond corticosteroids, a risk factor potentially life-threatening scleroderma renal crisis. Objectives Our aim was examine safety efficacy moderate dose prednisolone in dcSSc. Specific objectives were evaluate reduced pain disability, improved skin score, safe particular reference function Methods PRedSS set out as Phase II, multicentre, double-blind randomised controlled trial, converted open-label because Covid-19 pandemic. Patients receive either (approximately 0.3 mg/kg) matching placebo (or no treatment during open-label) 6 months. The co-primary endpoints Health Assessment Questionnaire Disability Index (HAQ-DI) modified Rodnan core (mRSS) at 3 Over 20 secondary included patient reported outcome measures reflecting pain, itch, anxiety depression, fatigue helplessness. 72 participants 1:1 planned anticipated yield 60 evaluable, giving over 80% power each ANCOVA analyses [assumptions; HAQ-DI (α = 0.025, δ -0.6, σ 0.9, ρ 0.6), mRSS -5.5, 8.2, 0.6)]. Mixed Models Repeated Measures (week 6, month 3, 6) fitted covariates trial arm, baseline anti-Scl-70 their interactions time point. An unstructured covariance matrix assumed primary focus being arm effect Results study terminated due pandemic consequently did meet recruitment target patients. Thirty-five (Table 1) (17 18 placebo/control, 25 phase), whom 34 completed assessment. adjusted mean difference between groups months score -0.10 (97.5% CI -0.29 0.10), p=0.25, -3.90 -8.83 1.03), p=0.070, both favouring but significantly. group experienced less helplessness than control months: scores -0.49, 95%CI (-0.93 -0.06), p=0.027, Hospital Anxiety Depression (HADS) -2.05, (-3.73 -0.37), p=0.018, -1.54, (-3.01 -0.07), p=0.040. There crises. Table 1. Baseline characteristics by allocation Characteristic Prednisolone (n=17) Control (n=18) Age (years) 52.7 (14.0) 55.3 (12.7) Female n (%) 10 (59) 9 (50) Duration thickening 1.6 (0.8) 1.7 Anti-topoisomerase-1 5 (29) (33) Anti-RNA polymerase III (35) 8 (44) (0.7) 18.8 (7.9) 23.5 (8.6) Values (standard deviation) unless stated otherwise Conclusion exemplified challenges running clinical investigational medicinal product associated increased infection Because prior recruitment, it underpowered, any conclusions extremely cautious. suggested some benefit from prednisolone, small sample indicates need further trial. References [1]Herrick AL et al. Clinical protocol: PRednisolone Systemic Sclerosis. J Scleroderma Rel Disord 2021; 6: 146-153. Acknowledgements This work funded Versus Arthritis Disclosure Interests Deb Griffiths-Jones: None declared, Yvonne Sylvestre Garcia: David Ryder: John Pauling Speakers bureau: Janssen, Consultant of: Boehringer Ingelheim, Permeatus Inc, Sojournix Pharma Astra Zeneca, Frances Hall Sobi, Roche, Grant/research support from: Alexion, Lilly, BMS, Actelion, Peter Lanyon Vifor pharma, Justin Mason Pfizer, Novartis, Janssen Roche., Christopher P Denton GSK, CSL Behring, Corbus, Gesynta, Servier, Arxx Therapeutics, Horizon, Ariane Herrick Arena, Boehringer-Ingelheim, Camurus, CSL-Behring, Gesynta