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4β-Hydroxycholesterol Level in Patients With Rheumatoid Arthritis Before vs. After Initiation of bDMARDs and

B M Wollmann1, S W Syversen2, E Lie2

  • 1Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.

Clinical and Translational Science
|December 20, 2016
PubMed

Insights

Biological drug treatment for rheumatoid arthritis did not restore suppressed CYP3A4 activity, as measured by 4β-hydroxycholesterol levels. Inflammatory markers correlated with 4βOHC post-treatment, suggesting non-CYP3A4-suppressive cytokines were reduced.

Area of Science:

  • Pharmacology
  • Immunology
  • Rheumatology

Background:

  • Systemic inflammation is known to suppress CYP3A4 enzyme activity.
  • 4β-hydroxycholesterol (4βOHC) is an endogenous metabolite reflecting CYP3A4 activity.
  • Rheumatoid arthritis (RA) is a systemic inflammatory disease.

Purpose of the Study:

  • To determine if biological disease-modifying antirheumatic drugs (bDMARDs) restore CYP3A4 activity in RA patients.
  • To assess changes in 4βOHC levels before and after bDMARD treatment.
  • To investigate correlations between 4βOHC and inflammatory markers (CRP, ESR) during RA treatment.

Main Methods:

  • Measured 4βOHC levels in 41 RA patients before and 2-5 months after initiating bDMARDs (TNFα, IL-6, or B-cell inhibitors).
  • Assessed C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as inflammatory markers.
  • Correlated 4βOHC levels with CRP and ESR before and after bDMARD therapy.

Main Results:

  • 4βOHC levels did not significantly change after bDMARD treatment (P=0.6).
  • No significant difference in 4βOHC was observed in patients treated with IL-6 inhibitors.
  • Significant correlations between 4βOHC and CRP (r=-0.40) and ESR (r=-0.34) emerged post-treatment, unlike pre-treatment.

Conclusions:

  • Initiation of bDMARDs in RA patients does not generally restore CYP3A4 enzyme activity.
  • Post-treatment correlations suggest reduction of non-CYP3A4-suppressive inflammatory cytokines.
  • Further research is needed to understand drug metabolism changes in inflammatory conditions.

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