POS0900 SYSTEMIC PHARMACOLOGICAL TREATMENT OF DIGITAL ULCERS IN SYSTEMIC SCLEROSIS: A SYSTEMATIC LITERATURE REVIEW

Background Digital ulcers (DU) are common in systemic sclerosis (SSc) and associated with reduced survival, high morbidity poor quality of life. Recommendations have previously been proposed for DU management yet there remains significant unmet patient need. Therefore the World Scleroderma Foundation Working Group intends to develop practical evidence based recommendations management. Objectives To summarise data on efficacy safety treatments SSc DU. Methods A systematic literature review May 2021 was performed. PubMed, MEDLINE, Embase, Web Science, Cochrane Library, Emcare (OVID) Academic Search Premier databases were searched original studies adult patients treated pharmacological treatment. Based PICO framework, eligibility criteria defined references independently screened by two reviewers. Reviewers assessed full text eligible articles. Owing interstudy heterogeneity narrative summaries used present data. Results The search strategy identified 1271 which 45 articles included. Seventeen randomised placebo controlled trials (RCT) pertaining PDE5 antagonists (PDE5i) (n=3), endothelin receptor (ERA) prostanoids (n=7), antiplatelet agents (n=1) other (n=3) (Table 1). No head RCT retrieved. All observational (OBS). Studies highly heterogeneous application differing definition DU, variable study criteria, clinical endpoints follow up periods. This limited calculation effect size comparison across studies. Table 1. Characteristics Author Year Intervention n Follow Outcome Favours intervention Hachulla 2016 Sildenafil 83 12 weeks Time healing - Andrigueti 2017 41 + Shenoy 2010 Tadalafil 24 6 New Khanna Macitentan 554 16 Matucci-Cerinic 2011 Bosentan 188 32 +- Korn 2004 122 Kawald 2008 IV iloprost 50 months Wigley 1992 35 10 1994 73 9 50% reduction score Seibold Treprostinil 148 20 Net burden Vayssairat 1999 Beraprost 107 25 % new Denton Selexipag 74 Number Lau 1993 Cicaprost 33 4 Abou-Raya Atorvastatin 84 Au Cyclophosphamide 158 Beckett 1984 Dipyridamole / aspirin 2 years Change general Nagaraja 2019 Riociguat 17 significantly superior comparator non different from DU: digital IV: intravenous SSc: Several found improved treatment: PDE5i, one showed prevention atorvastatin. Two demonstrated effective bosentan. OBS a total 621 improvements CCB, ERA, statins, N-acetylcysteine, ketanserin ERA. Regarding safety, all generally tolerated few serious adverse events. Treatment ceased 6.25-17.5% due treatment related side effects. Conclusion Despite several assessing it is not possible draw solid conclusions heterogeneity. Small shown benefit Large Our results highlight urgent need trial design generate more robust novel therapies guide Acknowledgements work supported Foundation. Disclosure Interests Nancy Maltez: None declared, Laura Ross: Michael Hughes Speakers bureau: Actelion Pharmaceuticals, Eli Lilly Pfizer outside submitted work., Jan Schoones: Murray Baron: Lorinda Chung Consultant of: Eicos, Corrado Campochiaro: Yossra A. Suliman: Dilia Giuggioli: Pia Moinzadeh Boehringer Ingelheim, Yannick Allanore: Christopher P Denton: Oliver Distler Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Corbus, CSL Behring, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Medscape, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi Topadur., Grant/research support from: Patent issued “mir-29 sclerosis” (US8247389, EP2331143), Tracy Frech: Daniel Furst: Dinesh Eicos Sciences Inc, Janssen, Thomas Krieg: Masataka Kuwana Speaker fees AbbVie, Asahi Kasei Pharma, Astellas, Chugai, Eisai, GlaxoSmithKline, Nippon Shinyaku, Ono Tanabe-Mitsubishi, consultancy Kissei, Mochida Marco Matucci-Cerinic: Janet Pope: Alessia Alunno: declared