1. Stratification in systemic sclerosis according to autoantibody status versus skin involvement: a study of the prospective EUSTAR cohort
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Muriel Elhai, Nanthara Sritharan, Marouane Boubaya, Alexandra Balbir-Gurman, Elise Siegert, Eric Hachulla, Jeska de Vries-Bouwstra, Gabriela Riemekasten, Jörg H W Distler, Edoardo Rosato, Francesco Del Galdo, Fabian A Mendoza, Daniel E Furst, Carlos de la Puente, Anna-Maria Hoffmann-Vold, Armando Gabrielli, Oliver Distler, Coralie Bloch-Queyrat, Yannick Allanore, Marco Matucci Cerinic, Ulrich Walker, Florenzo Iannone, Suzana Jordan, Radim Becvar, Otylia Kowal Bielecka, Maurizio Cutolo, Giovanna Cuomo, Claudia Kedor, Simona Rednic, Jérome Avouac, P. Vlachoyiannopoulos, C. Montecucco, Jiri Stork, Murat Inanc, Patricia E. Carreira, Srdan Novak, László Czirják, Michele Iudici, Eugene J. Kucharz, Elisabetta Zanatta, Katja Perdan-Pirkmajer, Bernard Coleiro, Gianluca Moroncini, Dominique Farge Bancel, Paolo Airò, Roger Hesselstrand, Mislav Radic, Yolanda Braun-Moscovici, Andrea Lo Monaco, Nicolas Hunzelmann, Raffaele Pellerito, Alessandro Giollo, Jadranka Morovic-Vergles, Christopher Denton, Madelon Vonk, Nemanja Damjanov, Jörg Henes, Vera Ortiz Santamaria, Stefan Heitmann, Dorota Krasowska, Paul Hasler, Michaela Kohm, Ivan Foeldvari, Gianluigi Bajocchi, Maria João Salvador, Bojana Stamenkovic, Carlo Francesco Selmi, Mohammed Tikly, Lidia P. Ananieva, Ariane Herrick, Ulf Müller-Ladner, Raffaele De Palma, Merete Engelhart, Gabriela Szücs, Cristina Sobrino Grande, Øyvind Midtvedt, David Launay, Valeria Riccieri, Ruxandra Maria Ionescu, Ami Sha, Ana Maria Gheorghiu, Cord Sunderkötter, Francesca Ingegnoli, Luc Mouthon, Vanessa Smith, Francesco Paolo Cantatore, Susanne Ullman, Carlos Alberto von Mühlen, Maria Rosa Pozzi, Kilian Eyerich, Piotr Wiland, Marie Vanthuyne, Juan Jose Alegre-Sancho, Kristine Herrmann, Ellen De Langhe, Branimir Anic, Maria Üprus, Sule Yavuz, Brigitte Granel, Carolina de Souza Müller, Joanna Busquets, Svetlana Agachi, Simon Stebbings, D'Alessandro Mathieu, Percival D. Sampaio-Barros, Lisa Stamp, Kamal Solanki, Douglas Veale, Esthela Loyo, Mengtao Li, Walid Ahmed Abdel Atty Mohamed, Antonietta Gigante, Fahrettin Oksel, Cristina-Mihaela Tanaseanu, Rosario Foti, Codrina Ancuta, Britta Maurer, Jacob van Laar, Cristiane Kayser, Nihal Fathi, Paloma García de la Peña Lefebvre, Jean Sibilia, Ira Litinsky, Giuseppina Abignano, Goda Seskute, Lesley Ann Saketkoo, Eduardo Kerzberg, Washington Bianchi, Ivan Castellví, Massimiliano Limonta, Doron Rimar, Maura Couto, François Spertini, Antonella Marcoccia, Sarah Kahl, Ivien M. Hsu, Thierry Martin, Sergey Moiseev, Lorinda S. Chung, Tim Schmeiser, Dominik Majewski, Zbigniew Zdrojewski, Julia Martínez-Barrio, Vera Bernardino, Sabine Sommerlatte, Yair Levy, Elena Rezus, Omer Nuri Pamuk, Piercarlo Sarzi Puttini, Hadi Poormoghim, Ina Kötter, Francis Gaches, Laura Belloli, Petros Sfikakis, Juliana Markus, Gary R Feldman, Ana-Maria Ramazan, H.U. Scherer, Marie-Elise Truchetet, Alain Lescoat, Lorenzo Dagna, J.M. van Laar, Lidia Rudnicka, Susana Oliveira, Fabiola Atzeni, Masataka Kuwana, Arsene Mekinian, Mickaël Martin, Yoshiya Tanaka, Elhai, M., Sritharan, N., Boubaya, M., Balbir-Gurman, A., Siegert, E., Hachulla, E., de Vries-Bouwstra, J., Riemekasten, G., Distler, J. H. W., Rosato, E., Del Galdo, F., Mendoza, F. A., Furst, D. E., de la Puente, C., Hoffmann-Vold, A. -M., Gabrielli, A., Distler, O., Bloch-Queyrat, C., Allanore, Y., Matucci Cerinic, M., Walker, U., Iannone, F., Jordan, S., Becvar, R., Kowal Bielecka, O., Cutolo, M., Cuomo, G., Kedor, C., Rednic, S., Avouac, J., Vlachoyiannopoulos, P., Montecucco, C., Stork, J., Inanc, M., Carreira, P. E., Novak, S., Czirjak, L., Iudici, M., Kucharz, E. J., Zanatta, E., Perdan-Pirkmajer, K., Coleiro, B., Moroncini, G., Farge Bancel, D., Airo, P., Hesselstrand, R., Radic, M., Braun-Moscovici, Y., Lo Monaco, A., Hunzelmann, N., Pellerito, R., Giollo, A., Morovic-Vergles, J., Denton, C., Vonk, M., Damjanov, N., Henes, J., Ortiz Santamaria, V., Heitmann, S., Krasowska, D., Hasler, P., Kohm, M., Foeldvari, I., Bajocchi, G., Salvador, M. J., Stamenkovic, B., Selmi, C. F., Tikly, M., Ananieva, L. P., Herrick, A., Muller-Ladner, U., De Palma, R., Engelhart, M., Szucs, G., Sobrino Grande, C., Midtvedt, O., Launay, D., Riccieri, V., Ionescu, R. M., Sha, A., Gheorghiu, A. M., Sunderkotter, C., Ingegnoli, F., Mouthon, L., Smith, V., Cantatore, F. P., Ullman, S., Alberto von Muhlen, C., Pozzi, M. R., Eyerich, K., Wiland, P., Vanthuyne, M., Alegre-Sancho, J. J., Herrmann, K., De Langhe, E., Anic, B., Uprus, M., Yavuz, S., Granel, B., de Souza Muller, C., Busquets, J., Agachi, S., Stebbings, S., Mathieu, D. A., Sampaio-Barros, P. D., Stamp, L., Solanki, K., Veale, D., Loyo, E., Li, M., Abdel Atty Mohamed, W. A., Gigante, A., Oksel, F., Tanaseanu, C. -M., Foti, R., Ancuta, C., Maurer, B., van Laar, J., Kayser, C., Fathi, N., Garcia de la Pena Lefebvre, P., Sibilia, J., Litinsky, I., Abignano, G., Seskute, G., Saketkoo, L. A., Kerzberg, E., Bianchi, W., Castellvi, I., Limonta, M., Rimar, D., Couto, M., Spertini, F., Marcoccia, A., Kahl, S., Hsu, I. M., Martin, T., Moiseev, S., Chung, L. S., Schmeiser, T., Majewski, D., Zdrojewski, Z., Martinez-Barrio, J., Bernardino, V., Sommerlatte, S., Levy, Y., Rezus, E., Nuri Pamuk, O., Sarzi Puttini, P., Poormoghim, H., Kotter, I., Gaches, F., Belloli, L., Sfikakis, P., Markus, J., Feldman, G. R., Ramazan, A. -M., Scherer, H. U., Truchetet, M. -E., Lescoat, A., Dagna, L., van Laar, J. M., Rudnicka, L., Oliveira, S., Atzeni, F., Kuwana, M., Mekinian, A., Martin, M., and Tanaka, Y.
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Rheumatology ,Immunology ,Immunology and Allergy - Abstract
Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81–0·84 for cutaneous only vs 0·84, 0·82–0·85 for antibody only vs 0·84, 0·83–0·86 for combined) or for progression-free survival (0·70, 0·69–0·71 vs 0·71, 0·70–0·72 vs 0·71, 0·70–0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46–0·71 for antibody only vs 0·29, 0·19–0·39 for cutaneous only) and disease progression (0·36, 0·29–0·46 vs 0·21, 0·14–0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70–0·74 for antibody only vs 0·66, 0·64–0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75–0·77 vs 0·71, 0·70–0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Funding: World Scleroderma Foundation.
- Published
- 2022