FRI0312 HYDROXYCHLOROQUINE SIGNIFICANTLY REDUCES SERUM MARKERS OF ENDOTHELIAL INJURY AND NEMO VIDEOCAPILLAROSCOPY SCORE IN SYSTEMIC SCLEROSIS: A 3-MONTHS PROSPECTIVE OBSERVATIONAL STUDY
Authors: Fabio Basta, Rosaria Irace, Alessia Borgia, Valentina Messiniti, Antonella Riccardi, Gabriele Valentini, Antonella Afeltra
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The most-commonly postulated model of disease progression in Systemic sclerosis (SSc) is based on the interplay between endothelial damage and tissue repair. Hydroxychloroquine (HCQ) is commonly used in systemic sclerosis (SSc) for the management of joint involvement [1]. In addition, HCQ showed to exert a protective role on endothelial dysfunction in several pathologic conditions [2] but no data exist in SSc. Objectives: aim of our study was to assess the effect of 3-months HCQ administration on serum levels of markers of endothelial injury and microvascular changes, assessed with NEMO score. <h3>Methods</h3> 20 SSc patients considered for treatment with HCQ 400 mg/day and 16 SSc patients not treated with HCQ were consecutively recruited, having clinical assessment, blood samples and nailfold capillaroscopy (NVC) at recruitment and after 3 months. Median age was 51.5 (19.5). Median onset of Raynaud's phenomenon was 83 (66) months. 29 patients had lSSc and 7 patients dSSc. Both groups had comparable vasoactive drugs, disease activity, duration and subtype. Any kind of overt vasculopathy was an exclusion criteria. The NEMO score was calculated as the total number of micro-haemorrhages (MHE) and micro-thrombosis (MT) and the giant capillaries (GC) score was calculated as the total number of GC [3]. Serum E-selectin, Endothelin-1 (ET-1), Vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor (VEGF-A) levels were assayed by Magnetic Luminex Assay, Human Premixed Multi-Analyte Assay (R&amp;D Systems). Plasma dimethyl arginine (ADMA) levels were determined by competitive ELISA (DLD Diagnosticka GMBH). Data were assessed with SPSS software version 25.0 and expressed as median and interquartile range. Wilcoxon rank-sum test, Mann-Whitney U test and Fisher's exact test were used for statistical evaluation. P values &lt; 0.05 were considered significant. Results: in the group treated with HCQ serum levels of E-Selectin (35.28 (16.88) ng/ml vs 30.84 (12.60) p = 0.004), VCAM-1 (847.30 (344.85) ng/ml vs 761.55 (396.87) p = 0.014) and ET-1 (12.25 (5.53) pg/ml vs 10.94 (4.35) pg/ml (p = 0.022) decreased significantly, as well as NEMO Score (7.5 (11.25) vs 6.5 (8) p = 0.001), MHEs (6 (7) to 5 (5.75) p = 0.003) and MTs (1 (4.5) to 0.5 (2) (p = 0.003). VEGF-A (p = 0.68), ADMA (p = 0.91) and GCs (p = 0.30) were unaffected. No significant improvements were observed among patients not treated with HCQ. <h3>Conclusion</h3> a significant improvement in endothelial function and microvascular involvement was achieved after three months of HCQ treatment. It is a novel finding in SSc which can represent a new therapeutic possibility for the prevention of microvascular complications of the disease <h3>References</h3> [1] Fernández-Codina A, Walker KM, Pope JE; Scleroderma Algorithm Group. Treatment Algorithms for Systemic Sclerosis According to Experts. Arthritis Rheumatol.2018;70:1820-1828. Doi: 10.1002/art.40560. [2] Virdis A, Tani C, Duranti E, Vagnani S, Carli L, Kühl AA, et al. Early treatment with hydroxychloroquine prevents the development of endothelial dysfunction in a murine model of systemic lupus erythematosus. Arthritis Res Ther. 2015;17:277. [3] Andracco R, Irace R, Zaccara E, Vettori S, Maglione W, Riccardi A, et al. The cumulative number of micro-haemorrhages and micro-thromboses in nailfold videocapillaroscopy is a good indicator of disease activity in systemic sclerosis: a validation study of the NEMO score. Arthritis Res Ther. 2017;19:133. <h3>Disclosure of Interests</h3> Fabio Basta: None declared, Rosaria Irace: None declared, Alessia Borgia: None declared, Valentina Messiniti: None declared, Antonella Riccardi: None declared, Gabriele Valentini Grant/research support from: MSD, Phizer, Consultant for: MSD, Phizer, biogen, Speakers bureau: MSD, amgen, biogen, lilly, sanofi, phizer, Antonella Afeltra Grant/research support from: MSD, PFIZER, ABBVIE, ROCHE, UCB, Speakers bureau: MSD, PFIZER, BMS, ROCHE, SANOFI