THU0331 INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS: DECLINE IN FORCED VITAL CAPACITY DOES NOT PREDICT FURTHER PROGRESSION IN THE FOLLOWING PERIOD
Authors: A. M. Hoffmann-Vold, H. Fretheim, B. Maurer, M. Durheim, Ø. Midtvedt, M. O. Becker, R. Dobrota, Ø. Molberg, S. Jordan, O. Distler
Journal: Annals of the Rheumatic Diseases (2020)

Background: In systemic sclerosis (SSc) patients with interstitial lung disease (ILD) approximately 30% show progressive ILD. It is unknown whether a progressive ILD period is followed by further lung function decline. In clinical practice, treatment is frequently initiated after observation of lung function decline over 6-12 months and lung function stabilization at follow up is often interpreted as treatment effect. Objectives: Assess the predictive ability of lung function decline over 12 months for further deterioration adjusted for known risk factors for ILD and treatment in two large and well characterized SSc cohorts. Methods: Patients with SSc-ILD by HRCT, fulfilling SSc classification criteria, from the Oslo and Zurich University Hospital were included. The first period with three consecutive annual forced vital capacity (FVC) measurements (i.e. at 0, 12 and 24 months, +/- 3 months) was used. Lung function decline was assessed by absolute changes in FVC% predicted. Moderately progressive ILD was defined as FVC decline of &gt;5-&lt;10% and significantly progressive ILD as FVC decline ≥10% in 12 months. Candidate predictors by experts (including SSc subtype, autoantibodies, disease duration, baseline and FVC decline in the first period, extent of lung and skin (mRSS) fibrosis, CRP, reflux, tendon friction rubs, O2 desaturation, dyspnea) for FVC decline in the second period were tested using logistic regression analysis. Treatment included low dose corticosteroids, mycophenolate mofetil; and other immunosuppressive treatment (cyclophosphamide, Rituximab and Tocilizumab). Results: In total, 240 SSc-ILD patients met the inclusion criteria (table). Of these 69 (29%) SSc-ILD patients showed progressive ILD in the first 12 months period; 34 (14%) with moderate (5-10%) and 35 (15%) with significant FVC decline (≥10%). Independent of FVC changes in the first period, 77 (32%) showed progressive ILD in the second period; 44 (18%) moderate and 33 (14%) significant FVC decline. Only 21 (9%) SSc-ILD patients had two progressive periods, and 115 (48%) were stable in the two 12 month’s periods; all independent of treatment. In multivariable logistic regression, progressive ILD in the first period (moderate, significant or combined FVC decline) was not predictive for progression in the following period. Of all applied risk factors, only mRSS was significantly predictive for further FVC decline, also when adjusted for age, gender and treatment (OR 1.03, 95%CI 1.00-1.08, p=0.035). Conclusion: Decline of FVC in one 12 months period did not predict further ILD progression in the following 12 months independent of treatment. These results have important clinical implications. Firstly, a decline of lung function in one period seems not to be the right indicator for initiating treatment. Secondly, stabilization of lung function under treatment initiated after ILD progression cannot necessarily be interpreted as a treatment response on the individual patient level. Table: First period Both periods SSc-ILD (n=240 ) ILD progression (n=69 ) ILD progression (n=21 ) Stable ILD (n=115 ) Age, years (SD) 48 (14.7) 49 (13.8) 50 (14.3) 46 (15.3) Male, n (%) 57 (24) 18 (26) 5 (24) 27 (24) Disease duration yrs, mean (SD) 10.2 (11.4) 9.8 (10.2) 8.8 (11.0) 10.8 (12.3) Disease duration &lt;3 years, n (%) 68 (28) 22 (32) 8 (38) 29 (25) Diffuse cutaneous SSc, n (%) 95 (40) 30 (44) 11 (52) 43 (27) Anti-topoisomerase I Ab, n (%) 84 (35) 27 (40) 9 (43) 42 (37) mRSS, mean (SD) 10 (9.3) 11 (10.2) 16 (13.0) 8 (8.3) CRPml, mean (SD) 3.6 (7.2) 3.3 (6.2) 4.4 (9.1) 3.1 (5.1) GERD, n (%) 148 (62) 44 (64) 15 (74) 70 (61) FVC % predicted 90 (20.3) 90 (21.9) 92 (21.7) 89 (19.3) DL CO % predicted 64 (17.9) 64 (16.6) 70 (11.3) 65 (17.5) Lung fibrosis &gt;20%, n (%) 55 (23) 16 (23) 4 (19) 27 (24) Mycophenolate Mofetil, n (%) 47 (20) 15 (22) 5 (24) 23 (20) Other immunosuppression, n (%) 79 (33) 22 (32) 9 (43) 42 (37) Corticosteroids, n (%) 62 (26) 18 (26) 8 (38) 28 (24) Disclosure of Interests: Anna-Maria Hoffmann-Vold Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion, Bayer, GlaxoSmithKline, Speakers bureau: Boehringer Ingelheim, Actelion, Roche, Håvard Fretheim: None declared, Britta Maurer Grant/research support from: AbbVie, Protagen, Novartis, congress support from Pfizer, Roche, Actelion, and MSD, Speakers bureau: Novartis, Mike Durheim Grant/research support from: BI, Consultant of: BI, Speakers bureau: BI, Øyvind Midtvedt: None declared, Mike O. Becker: None declared, Rucsandra Dobrota: None declared, Øyvind Molberg: None declared, Suzana Jordan: None declared, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche