4β‐Hydroxycholesterol Level in Patients With Rheumatoid Arthritis Before vs. After Initiation of bDMARDs and Correlation With Inflammatory State

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• 作者：BM Wollmann ; SW Syversen ; E Lie ; C Gjestad ; LL Mehus ; IC Olsen ; E Molden
• 刊名：Clinical and Translational Science
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：10
• 期：1
• 页码：42-49
• 全文大小：548.2KB
• ISSN：1752-8062

文摘

Systemic inflammation has been linked to suppressed CYP3A(4) activity. We determined 4β-hydroxycholesterol (4βOHC), an endogenous CYP3A4 metabolite, in patients with rheumatoid arthritis (RA) before and after treatment with biological disease-modifying antirheumatic drugs (bDMARDs). The 4βOHC was compared in 41 patients before and 2–5 months after initiating TNFα inhibitors (n = 31), IL-6 inhibitors (n = 5), or B-cell inhibitors (n = 5). Correlations between 4βOHC and inflammatory markers (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) were also tested before and after bDMARDs. 4βOHC did not differ following bDMARD treatment (P = 0.6), nor in patients who started with IL-6 inhibitors (median 51.6 vs. 50.6 nmol/L). The 4βOHC and CRP/ESR did not correlate before treatment (P > 0.5), but correlated significantly after bDMARDs (CRP = Spearman r -0.40; P < 0.01; ESR = r -0.34; P = 0.028) suggesting that mainly non-CYP3A4-suppressive cytokines were reduced during treatment. Thus, this study does not support a generally regained CYP3A4 phenotype in patients with RA following initiation of bDMARDs.