Pos1273 characteristics and Disease Course of Untreated Patients With Interstitial Lung Disease Associated With Systemic Sclerosis in a Real-Life Two-Center Cohort

Abstract

BackgroundInterstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc). Current guidelines consider that some patients may not require pharmacological treatment. To date, the characteristics and disease course of untreated SSc-ILD patients remain unknown.ObjectivesTo describe disease characteristics and disease course in untreated SSc-ILD patients in two well characterized SSc-ILD cohorts.MethodsWe included SSc patients from Zurich and Oslo who had a diagnosis of ILD on high-resolution computed tomography (HRCT) and available data on pulmonary function tests and treatment. The longitudinal study included patients with at least one follow-up visit. Patients were classified as treated if they had received a potential ILD modifying drug (immunosuppressive therapy or nintedanib). Treated and untreated patients were compared at baseline. ILD progression in the untreated group was defined as (i) decline in forced vital capacity (FVC) from baseline of ≥10% or (ii) decline in FVC of 5-9% associated with a decline in diffusing capacity for carbon monoxide (DLCO) of ≥15%, or (iii) start of any ILD modifying treatment during follow-up. In the untreated group, patients with ILD progression at any time point were compared with patients with no ILD progression during follow-up. Multivariable logistic regression was performed to identify (i) factors associated with no treatment of ILD at baseline and (ii) factors associated with progression in untreated patients. Covariates were selected based on clinical experience and literature evidence.ResultsThe cohort included 386 SSc-ILD patients, 301 (78%) had their first visit before 2016, 82 (21.5%) were males, mean age 57±14 years, mean disease duration 12±22 years, 120 (31%) had diffuse cutaneous SSc and 127/381 (33%) positive for anti-Scl70 antibodies. Of all, 290 (75%) were untreated at baseline. Untreated patients were more often women, had a longer disease duration, more frequently a limited cutaneous form, anticentromere antibodies and lower CRP levels. They had lower NYHA functional class, limited extent (<20%) of lung fibrosis, higher FVC (96±19 % vs. 81±22%), higher DLCO (69±20 % vs. 58±21) and better performances in the 6-minute walking test. In multivariable logistic regression, a less extensive disease on HRCT (OR: 3.71 [1.66-8.53], p=0.002) and anticentromere antibodies (OR: 5.18 [1.81-18.88], p=0.005) were independently associated with no treatment of ILD at baseline in our cohort. Over mean 56 months of follow-up, 135/233 (58%) untreated SSc-ILD patients showed progression. Among them, 116 progressed on lung function parameters. Half of the patients (68) progressed at the first follow-up visit (mean 14 months). Male sex, diffuse cutaneous subtype and extensive lung fibrosis were independently associated with lung progression during follow-up in untreated patients (Figure 1).Figure 1.ConclusionIn the past, a large number of SSc-ILD have been untreated, particularly patients with anti-centromere antibodies and overall less extensive ILD. However, during a follow-up of nearly 5 years, contrary to common belief, about 60% of untreated patients showed progression of ILD. With the development of effective and safe therapies for SSc-ILD, our results support a change in clinical practice in selecting patients for treatment.AcknowledgementsJason Hagedorn for help with the statistical analysis.Disclosure of InterestsMoritz Scheidegger: None declared, Alexandru Garaiman: None declared, Imon Barua: None declared, Mike O. Becker Speakers bureau: Mepha, Bayer, MSD, GSK, Amgen, Novartis and Vifor, Consultant of: Mepha, Bayer, MSD, GSK, Amgen, Novartis and Vifor, Hilde Jenssen Bjørkekjær Grant/research support from: Research grant from Janssen outside of the submitted work, Cosimo Bruni Consultant of: from Eli-Lilly, Boehringer Ingelheim outside of the submitted work, Grant/research support from:. Research grants from Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Scleroderma Clinical Trials Consortium (SCTC). Educational grants from AbbVie outside of the submitted work, Rucsandra Dobrota Consultant of: consulting or speaker fees from Actelion and Boehringer-Ingelheim outside of the submitted work, Grant/research support from: research grants from Articulum Fellowship, sponsored by Pfizer (2013-2014), Actelion, congress support from Amgen, outside the submitted work., Håvard Fretheim: None declared, Suzana Jordan: None declared, Malgorzata Maciukiewicz: None declared, Øyvind Midtvedt: None declared, Carina Mihai Consultant of: CM received consulting fees and/or honoraria from Boehringer Ingelheim, Janssen, MED Talks Switzerland, Mepha, and PlayToKnow AG outside of the submitted work, Grant/research support from: CM received congress support from Boehringer Ingelheim and Roche outside of the submitted work, Anna-Maria Hoffmann-Vold Speakers bureau: Boehringer Ingelheim, Jannsen, Medscape, Merck Sharp & Dohme and Roche outside of the submitted work, Consultant of: ARXX, Boehringer Ingelheim, Genentech, Jannsen, Medscape, Merck Sharp & Dohme and Roche outside of the submitted work, Grant/research support from: Boehringer Ingelheim, Jannsen outside of the submitted work, Oliver Distler Speakers bureau: Bayer, Boehringer Ingelheim, Janssen, Medscape outside of the submitted work, Consultant of: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant Siences, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Pfizer, Prometheus, Redxpharna, Roivant, Sanofi and Topadur outside of the submitted work, Grant/research support from: Kymera, Mitsubishi Tanabe, Boehringer Ingelheim outside of the submitted work, Muriel Elhai Consultant of: BMS outside the submitted work, Grant/research support from: Janssen for congress support outside of the submitted work.