Proton pump inhibitor use and long-term outcomes in systemic sclerosis: a real-life analysis from the EUSTAR database
Abstract
Objectives To investigate the association between proton pump inhibitor (PPI) use, all-cause mortality, and interstitial lung disease (ILD) progression in systemic sclerosis (SSc). Methods SSc patients enrolled in the EUSTAR registry with at least two clinical visits were included (EUSTAR CP141). PPI exposure was modeled 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, 8,637 (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 are commonly used in SSc characterised by a more severe multisystem phenotype. Only a marginal attenuation of ILD progression is observed, although absolute effects were small. These findings favour the generalised use of PPIs for symptomatic gastroesophageal reflux in SSc.
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BibTeX
@misc{bonomi2026proton,
title = {{Proton pump inhibitor use and long-term outcomes in systemic sclerosis: a real-life analysis from the EUSTAR database}},
author = {Francesco Bonomi and Giulia Bandini and Corrado Campochiaro and Veronica de Silvestri and Svetlana Agachi and Christina Bergmann and Oliver Distler and Brigitte Granel and Joerg Henes and Florenzo Iannone and Luca Idolazzi and Eduardo Kerzberg and Mohammad E Naffaa and Hadi Poormoghim and Mislav Radic and Marie-Elise Truchetet and Silvia Bellando Randone and Marco Matucci Cerinic and Zsuzsanna H Mcmahan and Michael Hughes},
howpublished = {HAL},
year = {2026},
month = sep,
doi = {10.1093/rheumatology/keag521},
url = {https://u-bordeaux.hal.science/hal-05770592v1},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Proton pump inhibitor use and long-term outcomes in systemic sclerosis: a real-life analysis from the EUSTAR database
AU - Francesco Bonomi
AU - Giulia Bandini
AU - Corrado Campochiaro
AU - Veronica de Silvestri
AU - Svetlana Agachi
AU - Christina Bergmann
AU - Oliver Distler
AU - Brigitte Granel
AU - Joerg Henes
AU - Florenzo Iannone
AU - Luca Idolazzi
AU - Eduardo Kerzberg
AU - Mohammad E Naffaa
AU - Hadi Poormoghim
AU - Mislav Radic
AU - Marie-Elise Truchetet
AU - Silvia Bellando Randone
AU - Marco Matucci Cerinic
AU - Zsuzsanna H Mcmahan
AU - Michael Hughes
PY - 2026
DA - 2026/09/18
PB - HAL
DO - 10.1093/rheumatology/keag521
UR - https://u-bordeaux.hal.science/hal-05770592v1
AB - Objectives To investigate the association between proton pump inhibitor (PPI) use, all-cause mortality, and interstitial lung disease (ILD) progression in systemic sclerosis (SSc). Methods SSc patients enrolled in the EUSTAR registry with at least two clinical visits were included (EUSTAR CP141). PPI exposure was modeled 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, 8,637 (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 are commonly used in SSc characterised by a more severe multisystem phenotype. Only a marginal attenuation of ILD progression is observed, although absolute effects were small. These findings favour the generalised use of PPIs for symptomatic gastroesophageal reflux in SSc.
ER -