POS0205 PROGNOSTIC VALUE OF CIRCULATING BIOMARKERS IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (SSc-ILD)
Authors: S. Assassi, M. Kuwana, C. Ittrich, M. Alves, O. Distler, S. Visvanathan
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Circulating biomarkers of epithelial injury and inflammation may be prognostic of progression of lung or skin fibrosis in patients with SSc-ILD. <h3>Objectives:</h3> To evaluate the prognostic potential of circulating biomarkers of epithelial injury (KL-6) and inflammation (CRP, CCL2) for FVC decline and change in modified Rodnan skin score (mRSS) over 52 weeks in the placebo group of the SENSCIS trial and to identify whether CRP or KL-6 levels can be used to delineate patients who will progress to FVC decline. <h3>Methods:</h3> Subjects had SSc with first non-Raynaud symptom in the prior ≤7 years and an extent of fibrotic ILD on high-resolution computed tomography (HRCT) ≥10%. Associations between baseline biomarker levels and i) rate of decline in FVC (mL/year) over 52 weeks, ii) absolute change from baseline in mRSS at week 52 were assessed in subjects who received placebo. Immunoassays were used to assess KL-6 and CCL2 levels. CRP was assessed on the Roche Cobas platform. Baseline biomarker levels were included in the models as continuous covariates or dichotomised by quantile-based cut-offs. Patients were delineated based on levels of KL-6 or CRP at baseline. <h3>Results:</h3> In total, 288 subjects received placebo. At baseline, subjects with KL-6 ≥1000 U/mL and CRP ≥6 mg/L had lower median FVC % predicted (72 vs 76) and higher median mRSS (11 vs 8) than subjects with KL-6 &lt;1000 U/mL and CRP &lt;6 mg/L. Higher baseline levels of selected biomarkers were associated (p&lt;0.05) with a greater rate of decline in FVC over 52 weeks (KL-6) and a worsening in mRSS at week 52 (CRP, CCL2). These biomarkers were not significantly correlated with one another, suggesting that they identified unique subsets of subjects with changes in FVC or mRSS. There were minimal differences in the levels of these biomarkers at baseline in the presence vs absence of mycophenolate (MMF) treatment. In analyses in which baseline biomarkers were dichotomised by quantile-based cut-offs, we identified a cut-off for KL-6 that was associated with FVC decline over 52 weeks (more vs less than 960.0 U/mL: -131.7 vs. -53.7 mL/year; p&lt;0.0072) (Figure 1) and cut-offs for CRP (more vs less than 2.5 ng/L: -0.7 vs. -2.8; p=0.0002) and CCL2 (more vs. less than 198.0 pg/mL: -0.8 vs. -2.8; p=0.0002) that were associated with change in mRSS at week 52. <h3>Conclusion:</h3> Biomarkers prognostic of progression of SSc/SSc-ILD based on worsening of mRSS and FVC decline have been identified in the placebo group of the SENSCIS trial. Levels of select biomarkers prognostic of progression were associated with different disease severities and have the potential to be utilized as part of patient selection in future trials in SSc/SSc-ILD. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> The SENSCIS trial was supported by Boehringer Ingelheim International GmbH. <h3>Disclosure of Interests:</h3> Shervin Assassi Professor Assassi has received consulting fees from AstraZeneca, aTyr Pharma, Boehringer Ingelheim, CSL Behring, Merck and TeneoFour., Professor Assassi has received grants/research support from aTyr Pharma, Boehringer Ingelheim and Janssen., Masataka Kuwana Payments made to Professor Kuwana from Boehringer Ingelheim, Ono Pharmaceutical, AbbVie, Janssen, Chugai, Asahi Kasei Pharma, Eisai., Professor Kuwana reports royalties or licenses from MBL., Payments made to Professor Kuwana from Boehringer Ingelheim, Chugai, Mochida, AstraZeneca, Kissei, GSK, Argenx. Professor Kuwana was a member of the SENSCIS trial Steering Committee., Payments made to Professor Kuwana's institution from Boehringer Ingelheim, Ono Pharmaceutical, MBL., Carina Ittrich Carina Ittrich is an employee of Boehringer Ingelheim., Margarida Alves Margarida Alves is an employee of Boehringer Ingelheim., Oliver Distler Professor Distler has received speaker fees from Bayer, Boehringer Ingelheim, Janssen, Medscape., Professor Distler has received consulting fees from 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., Professor Distler has received grants from Kymera, Mitsubishi, Tanabe., Sudha Visvanathan Sudha Visvanathan is an employee of Boehringer Ingelheim.