POS0317 THE PERFORMANCE OF DIFFUSING CAPACITY FOR MONOXIDE CARBON (DLCO) AND FORCED VITAL CAPACITY (FVC) IN PREDICTING THE ONSET OF SYSTEMIC SCLEROSIS (SSc)-INTERSTITIAL LUNG DISEASE (ILD) IN THE EUROPEAN SCLERODERMA TRIALS AND RESEARCH (EUSTAR) DATABASE
Authors: G. Lepri, C. Bruni, L. Tofani, A. Moggi Pignone, M. Orlandi, T. Sara, M. Hughes, F. Del Galdo, R. Irace, O. Distler, V. Riccieri, Y. Allanore, A. M. Gheorghiu, E. Siegert, J. De Vries-Bouwstra, E. Hachulla, M. Tikly, N. Damjanov, F. Spertini, L. Mouthon, A. M. Hoffmann-Vold, A. Gabrielli, S. Guiducci, M. Matucci-Cerinic, D. Furst, S. Bellando Randone
Journal: Annals of the Rheumatic Diseases (2021)

Background: In SSc, ILD is a major cause of morbidity and mortality. High resolution computed tomography (HRCT) is the gold standard for the diagnosis. Predictors of ILD onset are eagerly awaited to improve SSc-ILD management. Pulmonary function test (PFTs) are routinely performed to measure lung function changes. Objectives: Our aim was to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) in predicting the development of SSc-ILD. Methods: The longitudinal data of DLCO, FVC and ILD on HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t 0 ), after 12 (±4) (t 1 ) and 24 (±4) (t 2 ) months. Patients with negative HRCT for any sign of ILD both at t 0 and t 1 were included. Patients who presented or developed pulmonary hypertension during the study period were excluded. At baseline, demographic data, disease duration from Raynaud’s onset, disease subsets, autoantibodies and other laboratory and instrumental data were recorded. Results: 474/17805 patients were eligible for the study (403 females, 71 males): 26.0% dcSSc, 58.3% lcSSc, 220 (48.0%) patients with positive anticentromere antibodies (ACA) and 117 (25.4%) with positive antitopoisomerase I antibodies (Topo-I abs). Among all enrolled patients, 46 (9.7%) developed HRCT signs of ILD at t 2 . Patients with Topo-I abs showed an association with ILD development at t 2 (16.7% vs 7.8%, p=0.0031), contrarily ACA positive patients were negatively associated with ILD appearance after 2 years of follow-up (4.4% vs 14.4%, p=0.0001). Positive t 2 HRCT patients had a significant lower value of DLCO and FVC at all three assessments when compared to patients with a negative HRCT at t 2 (Table 1) and both t 0 DLCO and FVC values negatively correlated with ILD development (Table 1). The mean t 0 to t 1 change (Δ) of DLCO in patients with negative t 2 HRTC and positive t 2 HRCT were -0.5 (±12.6) and -1.0 (±15.1), respectively. The mean t 0 to t 1 ΔFVC in patients with negative t 2 HRTC and positive t 2 HRCT were -0.2 (±10.6) and 0.1 (±11.5), respectively. None of them predicted the appearance of ILD at t 2 (ΔDLCO: OR (IC) 0.997 (0.97-1.02), p=0.8024; ΔFVC OR (IC) 1.002 (0.97-1.03), p=0.8664). The data showed an association between t 0 DLCO value&lt;80% and ILD appearance after 2 years of follow-up [OR(IC): 3.09(1.49-6.40), p=0.0023]. Such association was not observed for t 0 FVC value&lt;80% [OR(IC): 1.95(0.81-4.68), p=0.1329]. The predictive capability of t 0 DLCO&lt;80% was moderate but stronger than FVC&lt;80% [AU ROC: 0.62 (0.56-0.69), 0.53 (0.48-0.59) respectively, p=0.0205]. Conclusion: Our data suggest that an impaired baseline DLCO (&lt;80%) may have a predictive value for the development of ILD on HRCT after 2 years of follow-up. Further rigorous prospective studies are warranted to understand the role of DLCO evaluation in the course of SSc. Table 1. DLCO and FVC values at t 0 , t 1 and t 2 values in patients with positive or negative HRCT for ILD at t 2 and their statistical differences. Patients without ILD at t2 (mean±SD) Patients with ILD at t2 (mean±SD) OR (95%CL) p-value DLCO at t 0 79.0 ± 16.6 69.9 ± 17.4 0.97 (0.95 - 0.99) 0.0006 DLCO at t 1 78.4 ± 16.8 68.9 ± 18.6 0.97 (0.95 - 0.98) 0.0005 DLCO at t 2 78.0 ± 17.0 65.1 ± 19.1 0.95 (0.93 - 0.97) &lt;0.0001 FVC at t 0 102.2 ± 17.3 94.6 ± 16.2 0.97 (0.96 - 0.99) 0.0052 FVC at t 1 101.9 ± 17.9 94.7 ± 16.5 0.98 (0.96 - 0.99) 0.0092 FVC at t 2 101.6 ± 17.6 94.5 ± 20.0 0.98 (0.96 - 1) 0.0126 Disclosure of Interests: Gemma Lepri: None declared, Cosimo Bruni Speakers bureau: CB reports personal fees from Actelion, personal fees from Eli Lilly, Grant/research support from: CB reports personal fees from Actelion, personal fees from Eli Lilly, grants from European Scleroderma Trial and Research (EUSTAR) group, grants from New Horizon Fellowship, grants from Foundation for Research in Rheumatology (FOREUM), grants from Fondazione Italiana per la Ricerca sull’Artrite (FIRA), outside the submitted work, Lorenzo Tofani: None declared, Alberto Moggi Pignone: None declared, Martina Orlandi: None declared, Tomasetti Sara Speakers bureau: Speaker’s fees for Roche and Boehringer Ingelheim, Mike Hughes: None declared, Francesco Del Galdo: None declared, Rosaria Irace: None declared, Oliver Distler Grant/research support from: OD (last three years) has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Valeria Riccieri: None declared, Yannick Allanore Speakers bureau: YA received personal fees from Boehringer, Sanofi, Menarini and Medsenic and grants from Alpine with regards to the management of systemic sclerosis, Grant/research support from: YA received personal fees from Boehringer, Sanofi, Menarini and Medsenic and grants from Alpine with regards to the management of systemic sclerosis, Ana Maria Gheorghiu: None declared, Elise Siegert: None declared, Jeska de Vries-Bouwstra: None declared, Eric Hachulla: None declared, Mohammed Tikly: None declared, Nemanja Damjanov: None declared, Francois Spertini: None declared, Luc Mouthon: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp &amp; Dohme and Roche; and grants from Boehringer Ingelheim., Consultant of: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp &amp; Dohme and Roche; and grants from Boehringer Ingelheim., Grant/research support from: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp &amp; Dohme and Roche; and grants from Boehringer Ingelheim., Armando Gabrielli: None declared, Serena Guiducci: None declared, Marco Matucci-Cerinic Speakers bureau: has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Grant/research support from: has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Daniel Furst: None declared, Silvia Bellando Randone: None declared