Abstract

The effect of hydroxychloroquine on endothelial dysfunction in patients with rheumatoid arthritis: A doubleblind randomized clinical trial

Author(s): Rudy Hidayat, Harry Isbagio, Idrus Alwi, Pradana Soewondo, Rianto Setiabudy, Sri Widia Jusman, Suzanna Immanuel, Kuntjoro Harimurti & Handono Kalim

Aim: The aim of this study was to evaluate the effect of hydroxychloroquine on endothelial dysfunction in rheumatoid arthritis patients by measuring soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-Selectin (sE-selectin) level as the biomarkers. Another aim was to assess the role of Homeostatic Model Assessment-Insulin Resistence (HOMA-IR), Free Fatty Acid (FFA), and oxidized Low- Density Lipoprotein (ox-LDL) in endothelial dysfunction improvement. Method: A double-blind randomized clinical trial was conducted on 37 patients with rheumatoid arthritis (with methotrexate treatment) at Rheumatology Outpatient Clinic of Cipto Mangunkusumo Hospital/Faculty of Medicine Universitas Indonesia, Jakarta. Patients with insulin, anti-hypertensive and other treatment which could affect sVCAM-1 and sE-Selectin level, were excluded. Eligible subjects were randomly assigned into two groups, 18 subjects were given hydroxychloroquine 400 mg/day and 19 subjects were given placebo, both given daily for 12 weeks. Serum sVCAM-1, sE-selectin, HOMA-IR, and ox-LDL level were examined using ELISA method, while FFA level using quantification colorimetric technique. Difference level of biomarkers in percentage before and after treatment and correlation between those biomarkers were evaluated. Result: A total of 37 subjects were enrolled in the study and randomized. During the observation, there were 6 drop-out subjects which were evenly distributed in both groups. Thirty one subjects analysed in this study, 15 subjects in the HCQ group and 16 subjects in the placebo group. Serum sVCAM-1 level decreased 15% (median) in HCQ treatment group after 12 weeks, while in placebo group, it increased 9%,7% (median) compared with pre-treatment level (p value <0,05). Serum sE-selectin level in HCQ group had a higher percentage of decrease compared with placebo group, but the difference was not significant. HOMA-IR, FFA, and ox-LDL level showed insignificant changes after HCQ therapy and had no correlation with sVCAM -1 and sE-selectin level. Conclusion: Treatment of 400 mg HCQ for 12 weeks in this study was proven to decrease sVCAM-1 level, but it was not proven to decrease sE-selectin, HOMA-IR, FFA, and ox-LDL level in RA patients. There were also no correlation between each HOMA-IR, FFA, and ox-LDL level with sVCAM-1 and sE-selectin level in this study.