Proton pump inhibitor use and long-term outcomes in SSc: a real-life analysis from the EUSTAR database
Year: 2026
Type: article
Study design: Observational Study
Abstract: OBJECTIVES: To investigate the association between proton pump inhibitor (PPI) use, all-cause mortality and interstitial lung disease (ILD) progression in SSc. METHODS: SSc patients enrolled in the EUSTAR registry with at least two clinical visits were included (EUSTAR CP141). PPI exposure was modelled as a time-varying variable. Inverse probability of treatment weighting (IPTW) based on propensity scores was applied to address confounding by indication. All-cause mortality was analysed using IPTW-weighted time-varying Cox models. ILD progression was assessed using functional endpoints (FVC decline ≥10% and ≥5%; DLCO decline ≥10%). Restricted mean survival time (RMST) was used to quantify absolute effects. Sensitivity analyses included a 6-month lag time. RESULTS: Out of 10 660 patients enrolled, 8637 (81.0%) were exposed to PPIs during a mean follow-up of 5.7 ± 4.3 years. They exhibited a more severe multisystem disease phenotype, including greater gastrointestinal, pulmonary and vascular involvement. After adjustment, PPI exposure was associated with higher all-cause mortality (HR 1.88, 95% CI 1.40-2.54), although the RMST difference at 5 years was minimal. As cause-specific mortality was unavailable, this association might reflect underlying disease severity rather than a direct drug effect. The use of PPI was not associated with a reduced risk of clinically meaningful FVC decline, while a modest attenuation of DLCO decline was observed, and absolute progression-free differences were limited. CONCLUSIONS: PPI is commonly used in SSc characterized by a more severe multisystem phenotype. Only a marginal attenuation of ILD progression is observed, although absolute effects were small. These findings favour the generalized use of PPIs for symptomatic gastroesophageal reflux in SSc.
Source: Rheumatology
Authors: Francesco Bonomi, Giulia Bandini, Corrado Campochiaro, Veronica De Silvestri, Svetlana Agachi, Christina Bergmann, Oliver Distler, Brigitte Granel, Joerg Henes, Florenzo Iannone, Luca Idolazzi, Eduardo Kerzberg, Mohammad E Naffaa, Hadi Poormoghim, Mislav Radic, Marie-Elise Truchetet, Silvia Bellando Randone, Marco Matucci Cerinic, Zsuzsanna H McMahan, Michael Hughes, EUSTAR Group, Ulrich Andreas Walker, Radim Bečvář, Elise Siegert, Yannick Allanore, Carlomaurizio Montecucco, Murat Inanc, Patricia Carreira, Gábor Kumánovics, Michele Iudici, Przemyslaw Kotyla, Elisabetta Zanatta, Gianluca Moroncini, Paolo Airò, Alexandra Balbir-Gurman, Annamaria Iagnocco, Josko Mitrovic, Christopher Denton, Madelon Vonk, Gianluigi Bajocchi, Tânia Santiago, Maria De Santis, David Launay, Valeria Riccieri, Andra Balanescu, Ana Maria Gheorghiu, Vanessa Smith, Addolorata Corrado, Mette Mogensen, Marie Vanthuyne, Juan Jose Alegre Sancho, Branimir Anić, Carolina de Souza Müller, Alberto Cauli, Kamal Solanki, Eiman Soliman, Edoardo Rosato, Britta Maurer, Sophie Blaise, Patricia Senet, Emmanuel Chatelus, Francesco Del Galdo, Ivan Castellví, Massimiliano Limonta, Antonella Marcoccia, Ina Koetter, Vivien Hsu, Dinesh Khanna, Carolina Teles, Yair Levy, Elena Rezus, Daniel Brito de Araujo, Giovanna Cuomo, Petros Sfikakis, Ana-Maria Ramazan, Jeska de Vries-Bouwstra, Alain Lescoat, Julia Spierings, Fabiola Atzeni, Masataka Kuwana, Mickaël Martin, Alfredo Guillén- Del-Castillo, Magda Parvu, Gonçalo Boleto, Nicoletta Del Papa, Enrico Selvi, Marta Mosca, Ulrich Gerth, Duygu Temiz Karadag, Anastas Batalov, Cristina Maglio, Miriam Retuerto, Monique Hinchcliff, Samar Tharwat, Ana Cristina Cordeiro, Francesco Benvenuti, Andrea-Hermina Györfi, Lilian Maria Lopez Nunez, Rossella De Angelis, Alejandro Brigante, Yasser El Miedany, Amato de Paulis, Chris Derk, Lijun Zhang, Bogdan Batko, Ivette Casafont Sole, Anna Lewandowska-Polak, Belén Atienza-Mateo, Tuncay Duruöz, Seda Colak, Janeth Villegas Guzmán, Claudia Mora-Trujillo, Boris Lindner, Maria Sole Chimenti, Samah A El-Bakry, Vera Ortiz-Santamaria, Jorge Rojas-Serran, Fatma Alibaz-Oner, Emine Duygu Ersözlü, Roberto Muñoz Louis, Minrui Liang, Massimo Triggiani, Anastasios Karamanakos, Bianca Dumitru, Lucy Carter, Beatrice André, Giuseppe Murdaca, Patricia Corzo Garcia, Theodora Simopoulou, Fabio Cacciapaglia, Tejaswini Ramineni, Gaia Mansuco, Jhonny Calizaya-Estrada, Gehad Gamal Maghraby, Mustafa Erdogan, Wen-Nan Huang, Graça Sequeira, Greta Pellegrino, Cláudia Vaz, Maya Buch, Joanna Kosałka-Węgiel
Institutions: Azienda Ospedaliero-Universitaria Careggi, IRCCS Ospedale San Raffaele, Nicolae Testemițanu State University of Medicine and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, University of Zurich, University Hospital Zurich, Assistance Publique Hôpitaux de Marseille, Hôpital Nord, Universitätsklinikum Tübingen, Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari, University of Bari Aldo Moro, University of Verona, Hospital Ramos Mejía, Bar-Ilan University, Western Galilee Hospital, Iran University of Medical Sciences, Klinički Bolnički Centar Split, University of Split, Centre National de la Recherche Scientifique, Université de Bordeaux, Centre Hospitalier Universitaire de Bordeaux, Immunology from Concept and Experiments to Translation, University of Florence, Vita-Salute San Raffaele University, The University of Texas Health Science Center at Houston, Manchester Academic Health Science Centre, University of Manchester, Manchester University NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Northern Care Alliance NHS Foundation Trust
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,597
OpenAlex ID: W7213636173