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

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.