Concordance and Prognostic Relevance of Different Definitions of Systemic Sclerosis Interstitial Lung Disease Progression

enrico De Lorenzis¹, Francesco Del Galdo², gerlando Natalello¹, Stefano Di Donato², lucrezia verardi¹, Vishal Kakkar², pier giacomo Cerasuolo¹, Francesco Varone³, Luca Richeldi³, Maria Antonietta D'Agostino¹ and Silvia Bosello¹, ¹Division of Rheumatology - Catholic University of the Sacred Heart, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy, ²University of Leeds - Leeds Institute of Rheumatic and Muskuloskeletal Medicine, Leeds, United Kingdom, ³Division of Pulmonology - Catholic University of the Sacred Heart, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy

Meeting: ACR Convergence 2023

Keywords: interstitial lung disease, Mortality, prognostic factors, Systemic sclerosis

Session Information

Date: Sunday, November 12, 2023

Title: (0609–0672) Systemic Sclerosis & Related Disorders – Clinical Poster I: Research

Session Type: Poster Session A

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

Background/Purpose: Interstitial Lung Disease (ILD) in systemic sclerosis (SSc) is a common complication that has varied progression rate and prognosis. Different progression definitions include minimal clinically important worsening of forced vital capacity (FVC MCIW), EUropean Scleroderma Trials and Research group (EUSTAR) progression, Outcome Measures in Rheumatology Clinical Trials (OMERACT) progression, and INBUILD/ Erice ILD working group progression. The aim of the study was to assess the concordance and prognostic value of these different definitions in SSc-ILD patients overall and specific clinical subsets.

Methods: Progression status in consecutive SSc-ILD patients was assessed over 24 months, comparing SSc-ILD-related mortality between progressors and non-progressors according to different definitions over the following 60 months. The prediction performances of different progression definitions were investigated with Cox Regression analysis and compared using Akaike information criterion (AIC) with a difference greater than 2 considered as evidence in favor of the model with the smaller AIC.

Results: The 245 SSc-ILD patients enrolled had a mean age of 54.6± 3.2 years and a median disease duration of 4 (IQR 2-8) years from the first non-Raynaud symptoms. Among these patients, 18.8% were males, and 54.7% had the diffuse LeRoy cutaneous variant, 59.2% had anti-Scl70 positivity, and 14.3% anti-centromere antibody positivity.

Twenty-six deaths were reported, and mortality was linked to progression per FVC MCIW (HR 2.27, 95% CI 1.03 – 4.97, p=0.041), OMERACT (HR 2.90, 95% CI 1.28 – 6.57, p=0.011), and INBUILD/Erice trial definitions (HR 11.02, 95% CI 2.38 – 51.08, p=0.002). Prognostic prediction using these four definitions was challenging in patients with longer disease duration, mild pulmonary function impairment, and pulmonary artery systolic pressure (PASP)≥40 mmHg. Erice criteria were superior in patients with disease duration >3 years, limited cutaneous variant, and PASP< 40 mmHg (ΔAIC >2). OMERACT criteria performed better in diffuse cutaneous variant patients with severe baseline functional impairment (ΔAIC >2).

Conclusion: The proposed SSc-ILD progression definitions are not interchangeable, risking potential misdiagnosis in up to a third of progressors. Regardless of criteria, progressors frequently showed diffuse skin disease variant, shorter disease duration, and worse functional impairment.

Comparisons of SSc-ILD survival of progressors and non-progressors according to different definitions.
Four main definitions are compared: A) FVC MCIW, B) OMERACT definition, C) EUSTAR definition D) Erice definition. Abbreviations: EUSTAR EUropean Scleroderma Trials and Research group; FVC MCIW minimal clinical important worsening of forced vital capacity, OMERACT Outcome Measures in Rheumatology Clinical Trials, SSc-ILD scleroderma-related interstitial lung disease.

Risk of SSc-ILD-related death in progressor patients across key clinical subsets
The patients were divided according to A) disease duration, B) LeRoy cutaneous variant, C) severity of baseline functional lung impairment and D) PASP values on echocardiography. The average risks of the whole population are also reported as comparators. The corresponding survival curves of the considered subgroup are displayed and compared on the right. Abbreviations: EUSTAR EUropean Scleroderma Trials and Research group; FVC MCIW minimal clinical important worsening of forced vital capacity, HR hazard ratio, OMERACT Outcome Measures in Rheumatology Clinical Trials, PASP pulmonary artery systolic pressure, PFT pulmonary function test, SSc-ILD scleroderma-related interstitial lung disease.

Disclosures: e. De Lorenzis: None; F. Del Galdo: AbbVie/Abbott, 5, arxx, 2, AstraZeneca, 2, 5, Boehringer-Ingelheim, 2, 5, capella, 2, Chemomab, 2, GlaxoSmithKlein(GSK), 2, Janssen, 2, Mitsubishi-Tanabe, 2, 5; g. Natalello: None; S. Di Donato: None; l. verardi: None; V. Kakkar: None; p. Cerasuolo: None; F. Varone: None; L. Richeldi: None; M. D'Agostino: AbbVie/Abbott, 2, 5, 6, Amgen, 2, 5, 6, Bristol-Myers Squibb(BMS), 2, 5, 6, Celgene, 2, 5, 6, Eli Lilly, 2, 5, 6, Janssen, 2, 5, 6, Merck/MSD, 2, 5, 6, Novartis, 2, 5, 6, Pfizer, 2, 5, 6, UCB, 2, 5, 6; S. Bosello: None.

To cite this abstract in AMA style:

De Lorenzis e, Del Galdo F, Natalello g, Di Donato S, verardi l, Kakkar V, Cerasuolo p, Varone F, Richeldi L, D'Agostino M, Bosello S. Concordance and Prognostic Relevance of Different Definitions of Systemic Sclerosis Interstitial Lung Disease Progression [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/concordance-and-prognostic-relevance-of-different-definitions-of-systemic-sclerosis-interstitial-lung-disease-progression/. Accessed .

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