Course of Progressive Lung Fibrosis in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD) in the EUSTAR Database

Anna-Maria Hoffmann-Vold¹, Yannick Allanore ², Margarida Alves ³, Nicole Graf ⁴, Paolo Airò ⁵, Lidia P. Ananyeva ⁶, László Czirják ⁷, Serena Guiducci ⁸, Eric Hachulla ⁹, Mengtao Li ¹⁰, Carina Mihai ¹¹, Gabriela Riemekasten ¹², Petros Sfikakis ¹³, Gabriele Valentini ¹⁴, Otylia Kowal-Bielecka ¹⁵ and Oliver Distler ¹⁶, ¹Dept. of Rheumatology, Oslo University Hospital, Oslo, Norway, Oslo, Norway, ²Dept. of Rheumatology A, Descartes University, APHP, Cochin Hospital, Paris, France, Paris, France, ³Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, Ingelheim am Rhein, Germany, ⁴Graf Biostatistics, Winterthur, Switzerland, Winterthur, Switzerland, ⁵UO Reumatologia e Immunologia Clinica, Spedali Civili di Brescia, Brescia, Italy, Brescia, Italy, ⁶VA Nasonova Institute of Rheumatology, Moscow, Russian Federation, Moscow, Russia, ⁷Dept. of Rheumatology and Immunology, University of Pécs, Pécs, Hungary, Pécs, Hungary, ⁸Dept. of Clinical and Experimental Medicine, Section of Rheumatology, University of Florence, Italy, Florence, Italy, ⁹Dept. of Internal Medicine and Clinical Immunology, Hôpital Claude Huriez, University of Lille, Lille, France, Lille, France, ¹⁰Dept. of Rheumatology, Peking Union Medical College Hospital (West Campus), Beijing, China, Beijing, China (People's Republic), ¹¹Dept. of Rheumatology, University Hospital Zurich, Zurich, Switzerland, Zurich, Switzerland, ¹²Dept. of Rheumatology and Clinical Immunology, University Medical Center Schleswig-Holstein, Lübeck, Germany, Lübeck, Germany, ¹³Joint Rheumatology Programme, National & Kapodistrian University of Athens Medical School, Athens, Greece, Athens, Greece, ¹⁴Dipartimento di Medicina di Precisione, II Policlinico U.O. Reumatologia, Napoli, Italy, Napoli, Italy, ¹⁵Dept. of Rheumatology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland, Bialystok, Poland, ¹⁶Dept. of Rheumatology, University Hospital Zürich, Zürich, Switzerland, Zürich, Switzerland

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: interstitial lung disease, pulmonary fibrosis and prognostic factors, Systemic sclerosis

Session Information

Date: Tuesday, November 12, 2019

Title: Systemic Sclerosis & Related Disorders – Clinical Poster III

Session Type: Poster Session (Tuesday)

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

Background/Purpose: The course of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is heterogeneous; some patients may experience rapid decline in lung function, while others have relatively stable disease. Large patient registries, such as The European Scleroderma Trials and Research (EUSTAR) database, can assist in mapping the trajectory of SSc-ILD and identifying patients at risk of progression.

Methods: Patients with SSc-ILD by high-resolution computed tomography, according to American College of Rheumatology/European League Against Rheumatism criteria, who were registered in the EUSTAR database with lung function measurements at baseline and after 12±3 months, and known disease duration, were eligible. Patients had to have ≥3 serial annual forced vital capacity (FVC) measurements available. The overall FVC course was assessed using absolute changes in FVC (% predicted) from baseline to last available FVC measurement. Patients were divided into five subgroups: improved FVC (FVC increase of ≥5%); stable FVC (FVC decline or increase of < 5%); minor FVC decline (FVC decline of 5–10%); moderate FVC decline (FVC decline of >10–20%); and major FVC decline (FVC decline of >20%). Absolute FVC changes (% predicted) in individual patients in each 12-month interval during the 5-year follow-up period were then determined and defined as follows: FVC improvement (FVC increase of ≥5%); stable FVC (FVC decline or increase of < 5%); minor decline (FVC decline of 5–10%) and moderate decline (FVC decline of >10%). Candidate predictors of FVC decline were selected based on published reports and expert opinion and tested using linear mixed-effect regression analysis.

Results: Of 826 eligible patients with SSc-ILD, 535 (65%) had ≥3 serial annual FVC measurements available. Overall FVC course among these patients is shown in Figure 1A: over the mean 5-year follow-up period, 335 (63%) patients showed overall improved or stable FVC, while 200 (37%) patients experienced overall mild, moderate or major FVC decline. Among patients whose overall FVC course was improved or stable, 157 (47%) experienced one or more 12-month intervals in which their FVC declined by ≥5% (Table 1). In total during the observation period, 357 patients (67%) experienced one or more 12-month intervals with an FVC decline of ≥5% (Table 1; Figure 1B). 80% of patients who experienced a 12-month interval of FVC decline did not experience further decline in the following 12-month period. Male sex, gastroesophageal reflux disease, skin score, disease duration, age, diffusion capacity of the lungs for carbon monoxide, New York Heart Association class and erythrocyte sedimentation rate were baseline risk factors for FVC decline over a mean of 5 years (Table 2).

Conclusion: These results support close monitoring of patients with SSc-ILD, as most patients experienced at least one 12-month interval with FVC decline during their 5-year follow-up period. Moreover, intervals of FVC decline were seen in some patients who appeared stable overall. Importantly, the risk factors for FVC decline identified herein could help identify patients at risk of disease progression.

Funding: Boehringer Ingelheim International GmbH, Germany

EUSTAR fig 1

FVC course among patients with SSc-ILD in the EUSTAR database -number of patients per category-: A. Overall FVC change during mean 5-year follow-up period; B. FVC changes during 12-month follow-up intervals; C. Subsequent FVC course during 12-month intervals among patients with improved or stable FVC during the first year of follow-up

EUSTAR table 1

Changes in FVC% predicted -n [%]- during 12-month follow-up intervals among patients with SSc-ILD in the EUSTAR database

EUSTAR table 2

Risk factors for FVC% change over the 5-year observation period in multivariable mixed-effect regression analysis in patients with SSc-ILD

Disclosure: A. Hoffmann-Vold, Actelion, 2, 5, Boehringer Ingelheim, 2, 5, GSK, 2, 5; Y. Allanore, Actelion, 2, 5, Alpine, 2, 5, Bayer, 2, 5, BMS, 2, 5, Boehringer Ingelheim, 2, 5, Bristol Myers Squibb, 5, Bristol-Myers Squibb, 2, 5, Genentech Roche, 2, 5, Inventiva, 2, 5, Italfarmaco, 2, 5, Sanofi, 2, 5, Servier, 2, 5; M. Alves, Boehringer Ingelheim, 3; N. Graf, Astellas, 5, Biotronik AG, 5; P. Airò, None; L. Ananyeva, Roche, 5, Boehringer Ingelheim, 5; L. Czirják, None; S. Guiducci, None; E. Hachulla, Actelion, 2, 5, Bayer, 2, 5, Chugai Pharma France, 8, GSK, 2, 5, Pfizer, 2, 5, Roche SAS, 5; M. Li, None; C. Mihai, Actelion, 5, Geneva, 5, Roche, 5, Rofarm, 5; G. Riemekasten, None; P. Sfikakis, None; G. Valentini, AbbVie, 2, 5, Abbvie, 2, 5, BMS, 2, 5, Lilly, 2, 5, Pfizer, 2, 5, Sanofi, 2, 5; O. Kowal-Bielecka, Bayer, 5, Boehringer Ingelheim, 5, Inventiva, 5, Medac, 5, Novartis, 5, Roche, 5; O. Distler, A. Menarini, 5, Abbvie, Acceleron, 5, Acceleron Pharma, 5, Actelion, 2, 5, 8, Actelion Pharmaceuticals, 2, 5, 8, 9, Amgen, 5, AnaMar, 2, 5, Bayer, 2, 5, 8, 9, Biogen Idec, 2, 5, Blade Therapeutics, 5, Boehringer Ingelheim, 2, 5, 8, 9, Catenion, 5, 9, ChemomAb, 2, 5, ChemomAB, 5, CSL Behring, 5, Ergonex, 5, espeRare Foundation, 2, 5, Genentech/Roche, 2, 5, GlaxoSmithKline, 5, GSK, 2, 5, Holds Patent mir-29 for the treatment of systemic sclerosis, 9, Inventiva, 2, 5, iQvia, 5, Italfarmaco, 2, 5, Italfarmco, 5, Lilly, 2, 5, med, 5, 8, medac, 5, Medac, 2, 5, MedImmune, 2, 5, Medscape, 5, 8, 9, Menarini, 8, Mepha, 8, Mitsubishi Tanabe, 2, 5, Mitsubishi Tanabe Pharma, 2, 5, MSD, 5, 8, Novartis, 2, 5, 8, 9, Patent, 9, Patent issued, 9, Pfizer, 2, 5, 8, Pharmacyclics, 2, 5, Roche, 5, 8, 9, Sanofi, 2, 5, Sinoxa, 2, 5, Target Bio Science, 5, Target BioScience, 5, UCB, 2, 5, 9, UCB in the area of potential treatments of scleroderma and its complications, 2, 5.

To cite this abstract in AMA style:

Hoffmann-Vold A, Allanore Y, Alves M, Graf N, Airò P, Ananyeva L, Czirják L, Guiducci S, Hachulla E, Li M, Mihai C, Riemekasten G, Sfikakis P, Valentini G, Kowal-Bielecka O, Distler O. Course of Progressive Lung Fibrosis in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD) in the EUSTAR Database [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/course-of-progressive-lung-fibrosis-in-patients-with-systemic-sclerosis-associated-interstitial-lung-disease-ssc-ild-in-the-eustar-database/. Accessed .

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