ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1195

MUC5B rs35705950 and Rheumatoid Arthritis Associated Interstitial Lung Disease Progression

Pierre-Antoine Juge1, Joshua Solomon2, Romain Garofoli3, Joyce S. Lee4, Fabienne Louis-Sidney5, Esther Ebstein1, Jorge Rojas-Serrano6, Montserrat I. Gonzalez-Perez6, Mayra Mejia6, Ivette Buendia-Roldan6, Ramces Falfan-Valencia7, Enrique Ambrocio-Ortiz7, Effrosyni Manali8, Spyros A. Papiris8, Theofanis Karageorgas9, Dimitrios Boumpas9, Katarina Antoniou10, Coline H.M. van Moorsel11, Joanne van Der Vis11, Yaël A. de Man11, Jan C. Grutters11, Caroline Kannengiesser12, Raphaël Borie13, Lidwine Wemeau-Stervinou14, Rene-Marc Flipo15, Hilario Nunes16, Yurdagul Uzunhan17, Dominique Valeyre18, Nathalie Saidenberg Kermanac'h19, Marie-Christophe Boissier20, Christophe Richez21, Thierry Schaeverbeke22, Tracy J. Doyle23, Paul Wolters24, Marie-Pierre Debray25, Catherine Boileau12, Raphaël Porcher26, Bruno Crestani13, David A. Schwartz4 and Philippe Dieude27, 1Université de Paris, Service de Rhumatologie Hôpital Bichat-Claude Bernard, AP-HP, Paris, France, 2National Jewish Health, Denver, CO, 3Hôpital Cochin, Service de Rééducation, Paris, Paris, France, 4Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA, Aurora, CO, 5Service de Rhumatologie, CHU de Fort de France, Martinique, France, Fort de France, France, 6Interstitial Lung Disease & Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, México City, México, Mexico, Mexico, 7HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas. Mexico City, Mexico, Mexico, Mexico, 82nd Pulmonary Medicine Department, University Hospital of Athens "Attikon", National and Kapodistrian University of Athens, Greece, Athens, Greece, 9Rheumatology and Clinical Immunology Unit, 4th Department of Internal Medicine, University Hospital of Athens "Attikon", National and Kapodistrian University of Athens, Greece, Athens, Greece, 10PS Department of Respiratory Medicine & Laboratory of Molecular & Cellular Pneumonology, Faculty of Medicine, University of Crete, Crete, Greece, Heraklion, Greece, 11St Antonius ILD center of excellence, St Antonius ziekenhuis, Nieuwegein, The Netherlands, Nieuwegein, Netherlands, 12Université de Paris, Hôpital Bichat, Service de Génétique, AP-HP, Paris, Paris, France, 13Université de Paris, Service de Pneumologie Hôpital Bichat-Claude Bernard, AP-HP, Paris, France, 14CHRU de Lille, Service de Pneumologie et Immuno-Allergologie, Centre de compétence des maladies pulmonaires rares, FHU IMMINENT, Lille, France, Lille, France, 15Lille University Hospital, Lille, France, 16Department of Pulmonology, Hôpital Avicenne, APHP, Bobigny, France, Bobigny, France, 17Hôpital Avicennes, Service de Pneumologie, AP-HP, Bobigny, Bobigny, France, 18Hôpital Avicenne, Service de pneumologie, AP-HP, Bobigny, Bobigny, France, 19Hôpital Avicennes, Service de Rhumatologie, AP-HP, Bobigny, Bobigny, France, 20Hôpital Avicenne, Service de Rhumatologie, AP-HP, Bobigny, Bobigny, France, 21Rheumatology Hospital, Pelligrin Hospital, Bordeaux University Hospital, Bordeaux, France, 22CHU de Bordeaux, Service de Rhumatologie, Bordeaux, France, 23Brigham and Women's Hospital, West Roxbury, MA, 24University of California, San Francisco, San Francisco, CA, 25Université de Paris, Service de Radiologie Hôpital Bichat-Claude Bernard, AP-HP, Paris, France, 26Centre d’Epidémiologie Clinique, AP-HP, Hôpital Hôtel-Dieu, F-75004 Paris, France, Paris, France, 27Université de Paris, Service de Rhumatologie Hôpital Bichat-Claude Bernard, AP-HP, Paris, Ile-de-France, France

Meeting: ACR Convergence 2020

Keywords: , ,

Session Information

Date: Sunday, November 8, 2020

Title: RA – Diagnosis, Manifestations, & Outcomes Poster III: Cardiopulmonary Aspects

Session Type: Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Rheumatoid arthritis (RA) associated interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF) sharephenotypic and genotypic similarities. Recently, in a large international genetic association case-control study, the IPF major risk factor, MUC5Brs35705950 promoter variant was found to be associated with RA-ILD. Regarding IPF, MUC5Brs35705950 T risk allele has been associated with better prognosis. However, the impact of MUC5Brs35705950 on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5Brs35705950 on pulmonary function tests (PFTs) evolution in patients with RA-ILD.

Methods: Patients with RA-ILD were included from France, USA, Mexico, Greece andtheNetherlands in this observationalinternational study. Patients were genotyped for MUC5Brs35705950 and PFTs data were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. We defined a significant deterioration of pulmonary function as an absolute decrease of at least 10% in FVC (expressed in percent of the predicted value) or a relative decrease in FVC of at least 10%, at two years from baseline. Individuals who underwent lung transplantation or who died before 2 years from baseline were considered as experiencing a significant decrease of pulmonary function.

Results: Out of 321 registered patients, 261 could be included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 y/o (IQR 57 – 71), 151 ever smokers (59.2%), 128 definite or possible usual interstitial pneumonia (UIP) (53.4%), 74 non-specific interstitial pneumonia (NSIP) (30.8%). Baseline median forced vital capacity (FVC) was 78.2% predicted (IQR 64.2 – 100.7) and Baseline diffusing capacity for carbon monoxide (DLCO) was 56.0% predicted (IQR 46.5 – 72.0). MUC5Brs35705950 minor allele frequency was 27.20%. Median follow-up was 3.5 years. Overall, there was a slight trend to decrease of 0.8% per year (CI95% 0.3 – 1.4). Additionally, an important inter-patient variability of FVC was found at baseline as well as during follow-up. DLOC shows a significant decrease of 1.8% per year on average (CI95% 1.2 – 2.3). A significant deterioration of PFTs at 2 years was observed for 33 of 256 evaluable patients. No baseline characteristics was associated with a significant deterioration of PFTs at 2 years, including the HRCT UIP pattern (OR=0.7; CI95% 0.3 – 1.6). MUC5Brs35705950 T risk allele was not associated with a better or worse deterioration of PFTs (OR=0.7; CI95% 0.2 – 2.2). No difference was found between MUC5Brs35705950 T risk allele carriers and non-carriers for transplant free survival (Figure 1.).

Conclusion: In this international multiethnicobservational study, PFTs from patients with RA-ILD were relatively stable over time andMUC5Brs35705950 T risk allele was not associated with a better or a worse evolution of PFTs.

Figure 1. Transplant-free survival of all patients (A) and according to MUC5B rs35705950 polymorphism (B).

Disclosure: P. Juge, Bristol-Myers Squibb Company, 5; J. Solomon, Pfizer Inc., 2, Boehringer Ingelheim, 2, Roche-Genentech, 9; R. Garofoli, None; J. Lee, None; F. Louis-Sidney, None; E. Ebstein, None; J. Rojas-Serrano, None; M. Gonzalez-Perez, None; M. Mejia, None; I. Buendia-Roldan, None; R. Falfan-Valencia, None; E. Ambrocio-Ortiz, None; E. Manali, None; S. Papiris, None; T. Karageorgas, None; D. Boumpas, None; K. Antoniou, None; C. van Moorsel, None; J. van Der Vis, None; Y. de Man, None; J. Grutters, None; C. Kannengiesser, None; R. Borie, None; L. Wemeau-Stervinou, None; R. Flipo, MSD France, 1, 2, Sanofi-Aventis, 1; H. Nunes, Boehringer Ingelheim, 1, 2, 3, Roche, 1, 2, 3, Galapagos, 1; Y. Uzunhan, None; D. Valeyre, None; N. Saidenberg Kermanac'h, None; M. Boissier, None; C. Richez, Bristol-Myers Squibb, 9, Amgen SAS, 5; T. Schaeverbeke, None; T. Doyle, None; P. Wolters, Boehringer Ingelheim, 2, Roche/Genentech, 2; M. Debray, None; C. Boileau, None; R. Porcher, None; B. Crestani, None; D. Schwartz, None; P. Dieude, None.

To cite this abstract in AMA style:

Juge P, Solomon J, Garofoli R, Lee J, Louis-Sidney F, Ebstein E, Rojas-Serrano J, Gonzalez-Perez M, Mejia M, Buendia-Roldan I, Falfan-Valencia R, Ambrocio-Ortiz E, Manali E, Papiris S, Karageorgas T, Boumpas D, Antoniou K, van Moorsel C, van Der Vis J, de Man Y, Grutters J, Kannengiesser C, Borie R, Wemeau-Stervinou L, Flipo R, Nunes H, Uzunhan Y, Valeyre D, Saidenberg Kermanac'h N, Boissier M, Richez C, Schaeverbeke T, Doyle T, Wolters P, Debray M, Boileau C, Porcher R, Crestani B, Schwartz D, Dieude P. MUC5B rs35705950 and Rheumatoid Arthritis Associated Interstitial Lung Disease Progression [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/muc5b-rs35705950-and-rheumatoid-arthritis-associated-interstitial-lung-disease-progression/. Accessed .

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