POS0230 CHARACTERISTICS AND DISEASE COURSE OF SSc-ILD PATIENTS WITH GASTROESOPHAGEAL REFLUX – AN ANALYSIS OF THE EUSTAR COHORT
Authors: E. Roth, C. Bruni, L. Petelytska, P. Carreira, J. K. De Vries-Bouwstra, A. Balbir-Gurman, V. Liakouli, G. Moroncini, C. Bergmann, L. Mouthon, C. P. Denton, M. De Santis, A. Cauli, P. Hasler, V. Bernardino, M. E. Truchetet, M. Vonk, F. Del Galdo, A. M. Hoffmann-Vold, O. Distler, M. Elhai
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Interstitial lung disease (ILD) is common in systemic sclerosis (SSc) and remains the leading cause of death. Gastroesophageal reflux disease (GERD) is frequent in SSc and has recently been recognized as an independent predictive factor for ILD progression. However, the characteristics of SSc patients with GERD and ILD are unknown, as well as predictive factors for the progression of ILD in this population. <h3>Objectives:</h3> We aimed (1) to analyze the prevalence of GERD in SSc-ILD patients in the EUSTAR database, (2) to assess the association of GERD with disease characteristics in SSc-ILD patients and (3) to identify the predictive factors for ILD progression in SSc patients with GERD. <h3>Methods:</h3> SSc-patients from the EUSTAR database fulfilling the ACR/EULAR criteria for SSc, with ILD confirmed on high-resolution computed tomography (HRCT) and available data on GERD were included. GERD was diagnosed if reflux/dysphagia was present at least once since the baseline visit. The longitudinal study included patients with at least two visits 12±3 months apart. Disease characteristics in patients with and without GERD were compared at baseline. The progression of lung fibrosis was defined as an FVC% decline of ≥ 10% or an FVC% decline of 5-9% in association with a DLCO% decline of ≥ 15% between two visits. Progression-free survival was defined as the time from baseline visit until ILD progression and/or death. Multivariable logistic regression was performed to identify factors associated with GERD in SSc-ILD patients at baseline. Prognostic factors for ILD progression, death and a combined outcome of death and ILD progression in SSc-ILD patients with GERD were tested by multivariate Cox proportional hazards regression. Multiple imputation was used to impute missing data. <h3>Results:</h3> 5462 SSc patients with ILD at baseline were included. GERD was reported in 4400 (80.6%) of the SSc-ILD patients. Patients with GERD were more often female, had a longer disease duration, more frequent diffuse cutaneous subset, musculoskeletal and intestinal symptoms as compared to patients without GERD. Additionally, they had more severe lung involvement with more severe respiratory symptoms, lower FVC, lower DLCO and worse performances at 6-minute walking test as compared to patients without GERD (Table 1). The diffuse cutaneous subtype (OR: 1.43 [1.18-1.72], p &lt; 0.001), lower DLCO (OR: 0.99 [0.99-1.00], p = 0.018) and treatment with ILD modifying drugs (OR: 1.97 [1.65-2.37], p &lt; 0.001) were independently associated with GERD at baseline. Of the SSc-ILD patients with GERD, 1747 were included in the longitudinal analysis. Over a mean follow-up of 3.3 years, progression was observed in 34.8% of SSc-ILD patients with GERD. An older age (HR: 1.02 [1.01-1.02], p &lt; 0.001), female sex (HR: 1.37 [1.07-1.75], p = 0.013) and the use of ILD modifying drugs (immunosuppressive and/or antifibrotic therapies) (HR: 1.41 [1.09-1.82], p = 0.009) were independent predictors for ILD progression in SSc-ILD patients. In total, 199 deaths were recorded over a mean follow-up of 5.9± 3.7 years. The use of PPI, as a surrogate marker of more persistent and severe GERD, independently predicted death (HR: 2.30 [1.52-3.48], p &lt; 0.001) and the combined outcome of death and ILD progression (HR: 1.28 [1.04-1.56], p = 0.017) (Figure 1). <h3>Conclusion:</h3> GERD is common in SSc-ILD patients and is associated with more severe lung involvement. The risk of ILD progression is increased in older patients and women with GERD and SSc-ILD, suggesting special attention to these populations. Current PPI use predicts death and ILD progression, supporting the hypothesis of the deleterious nature of persistent reflux in SSc-ILD progression and prognosis. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> EUSTAR collaborators. <h3>Disclosure of Interests:</h3> Eliane Roth: None declared, Cosimo Bruni Consulting for Boehringer Ingelheim., Research grants from Foundation for Research in Rheumatology (FOREUM), Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC), Scleroderma Research Foundation (SRF), Novartis Foundation for Bio-medical Research, EMDO Foundation. Educational grants from AbbVie and Wellcome Trust. Congress participation support from Boehringer Ingelheim., Liubov Petelytska: None declared, Patricia Carreira Patricia E Carreira has received fees for conferences and advisory boards (last 5 years): Janssen, Lilly, VivaCell, Emerald Health Pharmaceuticals, Gesynta Pharma, Boehringer Ingelheim, Abbie, Sanofi Genzyme, Mitsubishi Tanabe, Patricia E Carreira has received fees for conferences and advisory boards (last 5 years): Janssen, Lilly, VivaCell, Emerald Health Pharmaceuticals, Gesynta Pharma, Boehringer Ingelheim, Abbie, Sanofi Genzyme, Mitsubishi Tanabe, Jeska K. de Vries-Bouwstra Speaker fees from Dutch Society (payments made to institution), Boehringer Ingelheim (payments made to institution)., Consulting fees from Boehringer Ingelheim, Jansen-Cilag and Abbvie (payments made to institution), JdVB has received grant/research support to her institution from ReumaNederland (Dutch patient Society for Rheumatology), Nationale Vereniging voor mensen met lupus, APS, sclerodermie en MCTD (Dutch patient society), ARCH (Autoimmune Research and Collaboration Hub; Dutch interdisciplinary society for patients and caregivers), Janssen-Cilag, and Boehringer IngelheimJanssen-Cilag (payments made to institution)., Alexandra Balbir-Gurman Speaker for (pharmaceutical) companies Boehringer Ingelheim, Abbvie, Pfizer, Sanofi, Janssen, Scientific grant from Abbvie, Vasiliki Liakouli: None declared, Gianluca Moroncini: None declared, Christina Bergmann Consulting fees from Janssen and Boehringer-Ingelheim, not related to the content of this work., Luc Mouthon: None declared, Christopher P Denton: None declared, Maria De Santis consulting for Boehringer Ingelheim., Research grant from Gruppo Italiano Lotta alla Sclerodermia (GILS). Congress participation support from Abbvie, Lilly, Janssen, Grunenthal, Galapagos, Novartis, Alberto Cauli: None declared, Paul Hasler: None declared, Vera Bernardino Speaker fees from Astrazeneca and GSK., Marie-Elise Truchetet: None declared, Madelon Vonk received speaker fees from Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen Pharmaceutical Companies of Johnson &amp; Johnson, MSD, Novartis, and Roche; served as a data safety monitoring board member at Corbus; and is treasurer of EUSTAR and steering committee member of the ERN ReCONNET., received consulting fees from Boehringer Ingelheim and Janssen Pharmaceutical Companies of Johnson &amp; Johnson, received research grants from Boehringer Ingelheim, Ferrer, Galapagos and Janssen Pharmaceutical Companies of Johnson &amp; Johnson, Francesco Del Galdo has received fees and research support from: Abbvie, Argenx, Arxx, AstraZeneca, Boehinger-Ingelheim, Chemomab, GSK, Janssen, IAG, Merck, Mitsubishi-Tanabe, Novartis., has received fees and research support from: Abbvie, Argenx, Arxx, AstraZeneca, Boehinger-Ingelheim, Chemomab, GSK, Janssen, IAG, Merck, Mitsubishi-Tanabe, Novartis., Anna-Maria Hoffmann-Vold Boehringer Ingelheim, Boehringer Ingelheim, Janssen, Medscape, Merck Sharp &amp; Dohme, Novartis and Roche, ARXX, BMS, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck Sharp &amp; Dohme and Roche, Boehringer Ingelheim, Janssen, Oliver Distler OD has/had consultancy relationship with and/or has received research funding from and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus, Redxpharma, Roivant, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis" (US8247389, EP2331143). Co-founder of CITUS AG., OD has/had consultancy relationship with and/or has received research funding from and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus, Redxpharma, Roivant, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis" (US8247389, EP2331143). Co-founder of CITUS AG., OD has/had consultancy relationship with and/or has received research funding from and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus, Redxpharma, Roivant, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis" (US8247389, EP2331143). Co-founder of CITUS AG., Muriel Elhai: None declared.