Use of platelet inhibitors for digital ulcers related to systemic sclerosis: EUSTAR study on derivation and validation of the DU-VASC model
Alexandru Garaiman, Klaus Steigmiller, Cathérine Gebhard, Carina Mihai, Rucsandra Dobrota, Cosimo Bruni, Marco Matucci‐Cerinic, J. Henes, Jeska de Vries‐Bouwstra, Vanessa Smith, Andrea Doria, Yannick Allanore, Lorenzo Dagna, Branimir Anić, Carlomaurizio Montecucco, Otylia Kowal‐Bielecka, M. Martin, Yoshiya Tanaka, Anna‐Maria Hoffmann‐Vold, Ulrike Held, Oliver Distler, Mike Oliver Becker, EUSTAR Collaborators, Silvia Bellando-Randone, Gemma Lepri, Ulrich A. Walker, Florenzo Iannone, Suzana Jordan, Radim Bečvář, Ewa Gińdzieńska‐Sieśkiewicz, Katarzyna Karaszewska, Maurizio Cutolo, Giovanna Cuomo, Elise Siegert, Simona Rednic, Jérôme Avouac, Carole Desbas, Roberto Caporali, Lorenzo Cavagna, Patrícia Carreira, Srđan Novak, László Czirják, Michele Iudici, Eugene J Kucharz, Elisabetta Zanatta, Bernard Coleiro, Gianluca Moroncini, Dominique Farge Bancel, Paolo Airó, Roger Hesselstrand, Mislav Radić, Alexandra Balbir‐Gurman, Nicolas Hunzelmann, Raffaele Pellerito, Alessandro Giollo, Jadranka Morović‐Vergles, Christopher P. Denton, Nemanja Damjanov, Ann-Christian Pecher, Vera Ortiz-Santamaría, Stefan Heitmann, Dorota Krasowska, Paul Hasler, Ivan Foeldvari, Maria João Salvador, Bojana Stamenković, Carlo Selmi, Lidia P Ananieva, Ariane L. Herrick, Ulf Müller‐Ladner, Raffaele De Palma, Merete Engelhart, G Szücs, Carlos de la Puente, Øyvind Midtvedt, Torhild Garen, Håvard Fretheim, É. Hachulla, Valeria Riccieri, Ruxandra Ionescu, Ana Maria Gheorghiu, Cord Sunderkötter, Jörg H. W. Distler, Francesca Ingegnoli, Luc Mouthon, Francesco Paolo Cantatore, Susanne Ullman, Maria Rosa Pozzi, Kilian Eyerich, Piotr Wiland, Marie Vanthuyne, Juan José Alegre Sancho, Kristine Herrmann, Ellen De Langhe, Marko Barešić, Miroslav Mayer, Şule Yavuz, B. Granel, Carolina de Souza Müller, Svetlana Agachi
Abstract
OBJECTIVE: To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. METHODS: We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. RESULTS: Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. CONCLUSION: The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.