title: 4β-Hydroxycholesterol Level in Patients With Rheumatoid Arthritis Before vs. After Initiation of bDMARDs and Correlation With Inflammatory State.
abstract: 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.
authors.affiliation: Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: B M
authors.initials: BM
authors.lastname: Wollmann
authors.affiliation: Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: S W
authors.initials: SW
authors.lastname: Syversen
authors.affiliation: Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Lie
authors.affiliation: Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: C
authors.initials: C
authors.lastname: Gjestad
authors.affiliation: Department of Medicinal Biochemistry, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: L L
authors.initials: LL
authors.lastname: Mehus
authors.affiliation: Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: I C
authors.initials: IC
authors.lastname: Olsen
authors.affiliation: Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.|Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Molden
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D007249:Inflammation / Q000097:blood* / Q000150:complications / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D006888:Hydroxycholesterols; C099828:cholest-5-ene-3,4-diol; D002097:C-Reactive Protein