OP0038 IMPROVING RISK-STRATIFICATION OF RHEUMATOID ARTHRITIS PATIENTS FOR INTERSTITIAL LUNG DISEASE
Authors: J. Avouac, A. Steelandt, A. Cauvet, Y. Shirai, M. Kuwana, O. Distler, Y. Allanore
Journal: Annals of the Rheumatic Diseases (2020)

Background: Interstitial lung disease (ILD) is the most common pulmonary manifestation of rheumatoid arthritis (RA). It has emerged in recent series as a key prognostic factor including survival. The big challenge for rheumatologists is now the risk-stratification of RA patients for ILD. Chest high-resolution computed tomography (HRCT) is the gold standard for RA-ILD diagnosis, but costs and ionizing radiation may limit its use in clinical practice. Thus, circulating biomarkers could aid in this risk-stratification. Objectives: to evaluate the merit of 3 circulating markers for the diagnosis and the progression of RA-ILD. Methods: We included consecutive patients with RA, &gt;18 years of age, from 3 tertiary rheumatology centers (Paris, France, Tokyo, Japan and Zurich, Switzerland) over a 36-month period. All patients had at least one chest HRCT during the inclusion period. In the subset of French patients with ILD, HRCT lung images were obtained both at baseline (time of blood sample collection) and at a follow-up visit. The ILD status of patients with RA was established by chest HRCT. The chest HRCT pattern was classified as usual interstitial pneumonia, UIP or non-specific interstitial pneumonia, NSIP, by the local radiologist. Serum levels of lung epithelial-derived surfactant protein D , SDP, CCL-18 et Krebs von den Lungen-6 glycoprotein , KL-6 were measured by ELISA. Results: 147 patients were included (age: 66+/-12 ans, 69% of women, disease duration 11+/-10 years). Among these patients, 40 (27%) had fibrosing ILD on HRCT: 21 had a UIP pattern, 17 a NSIP pattern, and 2 had NSIP associated with chronic obstructive pulmonary disease. SPD (21.91+/-2.17 vs. 15.76+/-1.34 ng/mL, p=0.017) CCL18 (102+/-13 vs. 78+/-5 ng/mL, p=0.026) and KL6 (961+/-128 vs. 376+/-26 U/mL, p&lt;0.001) concentrations (Figure 1 A-C ) were significantly higher in patients with RA-ILD vs. unaffected RA patients. KL6 values ​​were also higher in patients with UIP compared to the other HRCT patterns and in patients with lesion extension&gt; 15% as compared to patients with milder disease. ROC curve analysis to assess the diagnostic abilities of the three markers for the diagnosis of RA-ILD showed a superiority of KL-6 (Area under the curve, AUC: 0.79 95% CI 0.72-0.86) compared to SPD (AUC: 0.66 95% CI 0.58-0.74) and CCL18 (AUC: 0.62, 95% CI 0.53-0.70) (Figure 1 D ). The sensitivity of KL-6 for the diagnosis of RA-ILD was 68% with a specificity of 83%. In the French subset with longitudinal data (n=15), extension of ILD was detected on 7 patients. Baseline KL6 serum levels were significantly increased in patients who experienced ILD progression (1987+/-1294 vs. 799+/-375 U/mL, p=0.027) (Figure 1 E ). The degree of ILD progression on HRCT was also proportional to baseline KL-6 concentrations (Figure 1 F ). Conclusion: KL-6 is relevant for the diagnosis and the prognosis of RA-ILD. It may be used as a circulating non-invasive first-line marker to stratify for indication of HRCT. Indeed, given the emerging lung issues in RA patients, this simple and highly reproducible marker, which is already available in routine care in some countries, could be a good prerequisite to chest HRCT in rheumatology clinics. Figure 1A-F. Concentrations of serum markers, diagnostic value and performance of KL-6 for the progression of rheumatoid arthritis-associated interstitial lung disease A-C, Concentrations of SPD (ng/mL) (A), CCL18 (ng/mL) (B) and KL-6 (U/mL) (C) in patients with with or without RA-associated ILD. D, ROC curve illustrating the diagnostic value of SPD, CCL18 and KL-6 for diagnosis of RA-ILD. E, Concentrations of KL-6 (U/mL) according to the progression on chest HRCT of RA-ILD. F, Degree of mean ILD progression on chest HRCT according to baseline KL-6 concentrations. *p&lt;0.05 and **** p &lt;0.0001 by Student’s t test Disclosure of Interests: Jérôme Avouac Grant/research support from: Pfizer, Bristol Myers Squibb, Consultant of: Sanofi, Bristol Myers Squibb, Abbvie, Boerhinger, Nordic Pharma, Speakers bureau: Sanofi, Bristol Myers Squibb Abbvie, MSD, Pfizer, Nordic Pharma, Alexia Steelandt: None declared, Anne Cauvet: None declared, Yuichiro Shirai: None declared, Masataka Kuwana Grant/research support from: Acetelion, Consultant of: Acetelion, Bayer, Chugai, Corbus Pharmaceuticals, CSL Behring and Reata Pharmaceuticals. He was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim), 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, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi