Lupus & antiphospholipid syndrome
The desethylhydroxychloroquine (DHCQ)/hydroxychloroquine (HCQ) metabolic ratio and CYP2C8 Genotype are associated with lipid profile improvement in systemic lupus erythematosus patients treated with hydroxychloroquine
Main finding · Lipid profile improvementResult — go to the resultAdjusted odds ratio 1.77 95% CI 1.17–2.68Authors' conclusion
The DHCQ/HCQ metabolic ratio (> 0.69) and specific CYP2C8 genotypes are associated with lipid profile improvement in HCQ-treated SLE patients.
Study context
- Population
- 459 Chinese adult patients with systemic lupus erythematosus (SLE) on stable HCQ therapy for at least 3 monthsChinese adults with SLE
- Participants
- 459 patients
- Exposure
- DHCQ/HCQ metabolic ratio > 0.69 vs ≤ 0.69, and CYP2C8 genotypes
- Outcome
- Lipid profile improvement: achieving at least one predefined lipid parameter (LDL-C < 1.8 mmol/L, TG < 1.7 mmol/L, non-HDL-C < 3.36 mmol/L, or HDL-C > 1.0 mmol/L) after treatment
Methodological detailsmultivariate logistic regression, stratified analysis, Whole-blood concentrations of HCQ, DHCQ and desethylchloroquine (DCQ) quantified, Genotyping of 10 single-nucleotide polymorphisms (SNPs) in CYP2C8, CYP2D6, CYP3A4 and CYP3A5
- Multivariate logistic regression
- Stratified analysis
- Whole-blood concentrations of HCQ, DHCQ and DCQ quantified
- Genotyping of 10 SNPs in CYP2C8, CYP2D6, CYP3A4 and CYP3A5
Main finding
Lipid profile improvement
Adjusted odds ratio
1.77
95% CI 1.17–2.68
P = 0.007
DHCQ/HCQ > 0.69vs DHCQ/HCQ ≤ 0.69
aOR 1.77 (95% CI 1.17–2.68); P = 0.007
As reported in the abstract
- Lipid profile improvement overall
- 187 patients (40.7%)
- Absolute concentrations of HCQ or its metabolites
- not associated
Observational data: associations, not effects.
Further findings
| Outcome | aOR (95% CI) | |
|---|---|---|
| Favorable CYP2C8 genotype plus DHCQ/HCQ metabolic ratio > 0.69rs10882521 TT + DHCQ/HCQ > 0.69vs DHCQ/HCQ ≤ 0.69e.g., for rs10882521 TT carriers | 5.96 (2.31–15.37) | |
| 0.050.21520Adjusted odds ratio (log scale) |
Lipid profile improvement by stratum
- Association particularly evident in females, patients younger than 45 years, low body mass index (BMI), and 400 mg daily HCQ dose
- Stratified analysis
CYP2C8 polymorphisms (rs10882521, rs17110453, rs7910936) and lipid profile improvement
- Significantly associated with distinct metabolite profiles and increased rates of lipid profile improvement, gene-dose effect
- P for trend = 0.006
CYP2D6, CYP3A4, CYP3A5 polymorphisms
- No significant associations
Original publication
The DHCQ/HCQ metabolic ratio and CYP2C8 Genotype are associated with lipid profile improvement in systemic lupus erythematosus patients treated with hydroxychloroquine. Arthritis Res Ther. Published 17 April 2026. doi:10.
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