BackgroundInterstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc). European consensus guidelines consider that some patients with mild disease might not need pharmacological treatment (1). Up to now, the disease characteristics and the disease course of non-treated SSc-ILD patients remain unknown.ObjectivesTo describe disease characteristics and the disease course of non-treated SSc patients with ILD.MethodsWe included patients from our local EUSTAR center registered since 2008, who had a diagnosis of ILD on high-resolution computed tomography (HRCT) and available data on pulmonary function tests and treatment. Longitudinal study included patients with at least one follow-up visit. Patients were classified as treated if they received a potential ILD modifying drug (immunosuppressive therapy or nintedanib). Treated and untreated patients were compared at baseline. Progression in the untreated group was defined as (i) forced vital capacity (FVC) decline from baseline of ≥10% or (ii) an FVC decline of 5-9% in association with a decline in diffusing capacity for carbon monoxide (DLCO) of ≥15%, or (iii) start of a ILD modifying treatment during follow-up. In the untreated group, patients who progressed at any time were compared with patients with stable disease during follow-up. Multivariable logistic regression was performed to identify (i) factors associated with non-prescription of a treatment in ILD patients at baseline and (ii) factors associated with progression in the untreated patients. Covariates were selected according to clinical experience and literature evidence.ResultsAmong 496 patients included in our cohort, 209 (42%) patients had ILD on baseline HRCT: 48/209 (23%) were males, median disease duration 8 [IQR: 4-12] years, 67/209 (32%) of diffuse cutaneous subset and 86/209 (41%) had anti-Scl70 antibodies.Among them, 142/209 (68%) did not receive any potentially ILD modifying treatments at baseline. Untreated patients were older (59 vs. 54 years), had a longer disease duration, were less frequently smokers, had more frequently anticentromere antibodies and lower levels of CRP. They had more frequently a limited extent (<20%) of lung fibrosis on HRCT, higher FVC (97.02 (±19.76) % vs. 78.29 (±19.23) %) and DLCO (72.10 (±18.97) % vs. 57.57 (±20.81) %), better performances in the 6 minute walking test and were less frequently treated with low dose of glucocorticoids.In multivariable logistic regression, older age (OR: 1.04 [1.01-1.08], p=0.021), a less extensive disease on HRCT (OR: 0.29 [0.09-0.90], p=0.037) and less frequent prescription of glucocorticoids (OR: 0.036 [0.12-0.92], p=0.037) were independently associated with absence of ILD modifying treatment prescription in our cohort.From the 142 untreated patients, 96 were followed-up for 64 [39-96] months. Of these, 56 (58%) patients showed progression of ILD, of whom 43 progressed by lung function parameters. Of these 56 patients, 31 (56%) progressed in the first 18 months. Diffuse cutaneous subtype (OR: 5.26 [1.26-27.62], p=0.031), shorter disease duration (OR: 0.95 [0.90-0.99], p=0.035) and oesophageal symptoms (reflux, dysphagia) (OR: 3.51 [1.12-12.18], p=0.036) at baseline were independent predictors of progression during follow-up in untreated patients.ConclusionA considerable number of SSc patients with ILD are not treated in clinical practice, in particular patients with limited cutaneous SSc, older age and an overall less extensive ILD. However, during a follow-up of 5 years, contrary to the common belief, about 60% of the untreated patients showed ILD-progression. The diffuse cutaneous subtype, shorter disease duration and oesophageal symptoms at baseline characterized these patients. With the development of effective and safe therapies for SSc-ILD, our results support a change in practice for selecting patients for treatment.References[1]Hoffmann-Vold A-M, et al. The Lancet Rheumatology. 2020;2(2):e71-e83.Disclosure of InterestsMoritz Scheidegger: None declared, Alexandru Garaiman: None declared, Carina Mihai Speakers bureau: Boehringer-Ingelheim, MED Talks Switzerland, Consultant of: Boehringer-Ingelheim (advisory board), Janssen (advisory board), Mike O. Becker Speakers bureau: Mepha, MSD, Novartis, GSK, Bayer and Vifor, Consultant of: Mepha, MSD, Novartis, GSK, Bayer and Vifor (advisory board fees), Rucsandra Dobrota Consultant of: Boehringer-Ingelheim (Advisory Board), Cosimo Bruni Speakers bureau: Eli-Lilly2018-2021, Actelion2019, Boehringer-Ingelheim2020-2021, Grant/research support from: AbbVie (educational grant 2021), Suzana Jordan: None declared, Håvard Fretheim Speakers bureau: Personal fees form Bayer and non-financial support from GSK and Actelion, outside the submitted work., Øyvind Midtvedt: None declared, Hilde Jenssen Bjørkekjær: None declared, Imon Barua: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Oliver Distler Speakers bureau: Bayer, Boehringer Ingelheim, Janssen, Medscape, Consultant of: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and Topadur, Grant/research support from: Kymera, Mitsubishi Tanabe, Boehringer Ingelheim, Muriel Elhai Speakers bureau: Speaker fees: BMS outside the submitted work
BackgroundInterstitial lung disease (ILD) in primary Sjögren’s syndrome (pSS) has been reported to be present in 10-15% of patients, but pSS-ILD behavior over time is not well characterized.ObjectivesAssess the pattern of ILD in pSS, its disease behavior and factors associated with disease progression in a well-characterized pSS-ILD cohort.MethodsAll pSS patients from the Oslo University Hospital (OUH) were included if ILD was diagnosed on HRCT. Clinical characteristics, lung function tests including forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) and ILD pattern on HRCT assessed by a radiologist were evaluated. We determined ILD progression, defined as absolute FVC decline >5% or absolute DLCO decline >10% over 12 +/-6 months and increasing extent of ILD on HRCT over the observation period. Factors associated with disease progression were chosen based on expert opinion. Descriptive analyses were conductedResultsOf 702 pSS patients followed at OUH, we identified 60 pSS patients with ILD with 33 (55%) having follow-up at 12 months (Table 1). Patients with pSS-ILD were characterized by high number of males (18%) and by frequent other extra-pulmonary organ involvement (48%) (Table 1). Mean time from pSS diagnosis to ILD diagnosis was 7.4 years. In 67% ILD was diagnosed after pSS, in 13% simultaneously, in 11% before pSS diagnosis and in 9% unknown. In total, 28 (47%) were diagnosed with lymphocytic interstitial pneumonia (LIP) and 32 (53%) with reticular pattern on HRCT. Over mean follow-up of 10.9 months (SD 4.2), 7/33 (21%) showed a FVC >5% decline, 9/32 (28%) a DLCO >10% decline and 12 (36%) had at least one of these defined lung function declines on standard of care treatment. Treatment was registered as ever used and by any indication. Over an observation period of 15.4 (SD 10.6) years, 27/47 (45%) showed any ILD progression on HRCT. HRCT pattern was not associated with risk of >10% DLCO decline or ILD progression on HCRT. >5% FVC decline occurred more frequently in patients with reticular pattern compared to LIP (6/17 (35%) vs 1/16 (6%), p=0.041). Factors significantly associated with ILD progression on lung function included higher baseline FVC (99% (SD16.4) vs 87% (SD14.9), p=0.032), higher DLCO (81% (SD13.1) vs 67% (SD17.4), p=0.020), increased CRP (2/10 (20%) vs 0/16 (0%), p=0.045) and presence of polyneuropathy (2/9 (22%) vs 1/17 (6%), p=0.045).Table 1.Clinical characteristics, demographics and outcome of pSS with ILDpSS-ILD(n=60)Age at pSS diagnosis, y (SD)50 (21.9)Time from pSS to ILD diagnosis, y (SD)7.4 (8.9)Male sex, n (%)11 (18)Anti-SSA AB, n/50 (%)46 (92)Increased CRP, n/47 (%)7 (15)Low complements, n/49 (%)5 (10)Extra-pulmonary involvement, n/46 (%)22 (48)Deceased, n (%)10 (17)Pulmonary involvementFVC% predicted (SD)91 (18.7)FVC decline>5%, n/33 (%)7 (21)DLCO% predicted (SD)70 (20.7)DLCO decline >10%, n/32 (%)9 (32)ILD progression on HRCT, n/47 (%)27 (45)Treatment during follow upRituximab, n (%)11 (18)Any other immunosuppressive, n (%)20 (33)Hydroxychloroquine, n (%)16 (27)Nintedanib, n (%)1 (2)Lung transplant, n (%)1 (2)ConclusionA substantial number of patients with pSS-ILD progressed during the time of observation. This highlights the importance of close monitoring and active consideration of treatment options in pSS-ILD. Recommendations for disease management including screening, diagnosis, disease monitoring and treatment for pulmonary involvement in pSS are lacking to date, but are highly needed.Disclosure of InterestsAnna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Håvard Fretheim Consultant of: Bayer, Grant/research support from: Jansen, Phuong Phuong Diep Speakers bureau: Boehringer Ingelheim, Karoline Lerang: None declared, Helena Andersson: None declared, Øyvind Midtvedt: None declared, Torhild Garen: None declared, Mike Durheim Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim and Roche, Grant/research support from: Boehringer Ingelheim and Roche, Trond M Aaløkken Speakers bureau: Boehringer Ingelheim, Øyvind Palm: None declared, Øyvind Molberg: None declared
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.