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Publications

Journal Article Ppublish

PubMed: 42760267 DOI: 10.1093/rheumatology/keag521

Proton pump inhibitor use and long-term outcomes in SSc: a real-life analysis from the EUSTAR database.

Rheumatology (Oxford) 65(10)

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

Affiliations

  • Department of Internal Medicine, University Hospital Careggi, Florence, Italy.
  • Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy.
  • Discipline of Rheumatology and Nephrology, Department of Internal Medicine, Nicolae Testemițanu State University of Medicine and Pharmacy, Chisinau, Moldova.
  • Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Deutsches Zentrum Immuntherapie (DZI), FAU Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Department of Internal Medicine, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France.
  • Center for Interdisciplinary Rheumatology, Immunology and Autoimmune Diseases (INDIRA) and Department for Internal Medicine II (Hematology, Oncology, Rheumatology and Clinical Immunology), University Hospital Tuebingen, Tuebingen, Germany.
  • Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Polyclinic Hospital, University of Bari, Bari, Italy.
  • Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy.
  • Departamento de Medicina Interna, Hospital General de Agudos J.M Ramos Mejía, Buenos Aires, Argentina.
  • The Rheumatology Unit, Galilee Medical Center, Nahariyya, Israel.
  • The Azrieli's Faculty of Medicine, Bar-Ilan University, Safed, Israel.
  • Iran University of Medical Sciences, Tehran, Iran.
  • Department of Internal Medicine, Division of Rheumatology, Allergology and Clinical Immunology, Center of Excellence for Systemic Sclerosis in Croatia, University Hospital of Split, Split, Croatia.
  • Internal Medicine Department, School of Medicine, University of Split, Split, Croatia.
  • ImmunoConcEpT, UMR 5164, University Bordeaux, CNRS, Bordeaux, France.
  • CHU de Bordeaux, FHU ACRONIM, Centre national de référence des maladies auto-immunes et systémiques rares Est/Sud-Ouest (RESO), Bordeaux, France.
  • Department of Experimental and Clinical Medicine, Division of Rheumatology, Careggi University Hospital, University of Florence, Florence, Italy.
  • Vita Salute San Raffaele University, Milano, Italy.
  • Inflammation Fibrosis and Ageing Initiative, (INFLAGE), Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milano, Italy.
  • Division of Rheumatology, UTHealth Houston, Houston, TX, USA.
  • Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
  • Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Salford, UK.
  • NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK.

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.

MeSH

Mortality, Phenotype, Rheumatic Diseases, Proton Pump Inhibitors, Proton Pumps, Lung Diseases, Interstitial