FRI0265 IS AN IMPROVEMENT IN SKIN FIBROSIS ASSOCIATED WITH BETTER OUTCOME IN PATIENTS WITH SYSTEMIC SCLEROSIS? A EUSTAR ANALYSIS
Authors: A. Wyss, S. Jordan, N. Graf, E. Siegert, L. Czirják, A. Doria, A. Giollo, E. Rosato, A. M. Hoffmann-Vold, A. Gabrielli, O. Distler
Journal: Annals of the Rheumatic Diseases (2020)

Background: In previous studies, we showed that in patients with diffuse cutaneous systemic sclerosis (dcSSc), worsening of skin fibrosis predicts later decline in lung function and worse survival. However, in many patients, an improvement of skin fibrosis is the natural course of dcSSc, and many current clinical trials are designed to show improvement of skin fibrosis rather than prevention of skin fibrosis progression. Objectives: To investigate whether an improvement in skin fibrosis is associated with less progression of visceral organ involvement and better overall-survival during follow-up. Methods: We evaluated patients from the European Scleroderma Trials and Research Group (EUSTAR) database with diffuse cutaneous systemic (dcSSc), baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 follow-up visit. Regression of skin fibrosis was defined as a decrease in mRSS &gt;5 and ≥25% and progression as increase by the respective numbers from baseline to 12±3 months. Outcomes were pulmonary progression, cardiac progression, intestinal progression, new onset of scleroderma renal crisis and all-cause death using recently specified definitions (1). Associations between skin changes and outcomes were evaluated by Kaplan-Meier analysis and multivariable Cox regression. Results: Of 1257 included patients, 282 (22.4%) showed a regression of skin fibrosis, 883 (70.2%) were categorized as stable patients and 92 (7.3%) showed progression of skin fibrosis at 12±3 months. Median long-term follow-up for organ involvement/death was 4.2 years. Cox regression analyses indicated that skin fibrosis regression had a significantly lower probability of later FVC decline ≥10% than non-regressive (stable and progressive) patients when controlled for baseline mRSS (p=0.013). No significant association of skin fibrosis regression was found with other organ manifestations or all-cause death. Conversely, associations of skin fibrosis progression were found for later FVC decline ≥10% with a more significant p-value (p&lt;0.001, Figure 1), and there was also an association with all cause death (p=0.026). Conclusion: Progression of skin fibrosis is stronger associated with organ changes and all-cause death at follow up than improvement of skin fibrosis. These data suggest a prevention of progression paradigm for clinical practice. They also suggest that clinical trials designed for prevention of skin fibrosis progression are more meaningful for long-term outcome of SSc patients than trials designed to show improvement of skin fibrosis References: [1]Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort. Wu W, Jordan S, Graf N, de Oliveira Pena J, Curram J, Allanore Y, Matucci-Cerinic M, Pope JE, Denton CP, Khanna D, Distler O; EUSTAR Collaborators. Ann Rheum Dis. 2019 May;78(5):648-656 Disclosure of Interests: Anja Wyss: None declared, Suzana Jordan: None declared, Nicole Graf: None declared, Elise Siegert Grant/research support from: Actelion, Consultant of: AEC, Speakers bureau: NA, László Czirják Consultant of: Actelion, BI, Roche-Genentech, Lilly, Medac, Novartis, Pfizer, Bayer AG, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Alessandro Giollo: None declared, Edoardo Rosato: None declared, Anna-Maria Hoffmann-Vold Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion, Bayer, GlaxoSmithKline, Speakers bureau: Boehringer Ingelheim, Actelion, Roche, Armando Gabrielli: None declared, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche