Background/Purpose: Hydroxychloroquine (HCQ) levels can be measured in whole blood as well as in serum but both methods have never been compared. Cut offs for non-adherence (200 ng/mL or lower) have been established in whole blood.
The aims of this study were to compare the interest of whole blood versus serum levels for drug monitoring of HCQ, and since it would be very interesting to retrospectively assess severe non-adherence in clinical trials or in large cohort of patients in which only serum samples are usually available, to evaluate if HCQ serum level cut off could be determined to identify non-adherent patients.

Methods: The HCQ and desethylchloroquine (DCQ) levels were measured in serum and whole blood from 573 systemic lupus erythematosus (SLE) patients. The risk factors for active SLE (SLEDAI score >4) were identified using multiple logistic regression. HCQ serum level was also measured in 68 additional non-adherent patients (whole blood HCQ level < 200 ng/mL).

Results: The mean HCQ and DCQ levels were 916 ± 449 and 116 ± 55 ng/mL in whole blood, respectively; and 469 ± 223 and 63 ± 31 ng/mL in serum, respectively. The mean ratio of serum /whole blood level for HCQ was 0.53 ± 0.15.
A strong positive correlation was found between serum and whole blood levels of HCQ (rho=0.837 [CI95% 0.810-0.860], p< 0.0001), and DCQ (rho=0.771 [CI95% 0.736-0.802], p< 0.0001). In the multivariate analysis, only corticosteroids (p=0.044), immunosuppressant (p=0.027), HCQ whole blood level (p=0.023) and hemoglobin (p=0.009) were identified as an independent risk factor of active SLE but serum HCQ level was not.
Given that the mean ratio of serum/whole blood level for HCQ was 0.53, we extrapolated that serum HCQ level cut offs of 106 and 53 ng/mL would correspond to the previously used cut-off of 200 and 100 ng/mL of HCQ in whole blood. The positive and negative predictive values of serum HCQ < 106 ng/ml to detect non-adherence (defined by blood HCQ < 200 ng/ml) were 86.8% and 85.7%, respectively.
All serum HCQ levels of patients exhibiting whole blood HCQ below the detectable levels (< 50 ng/mL) were also below the detectable levels for serum (37.5 ng/mL).

Conclusion: These data suggest that whole blood is better than serum when assessing pharmacokinetic/pharmacodynamic relationship of HCQ. When whole blood is not available, our results support the use of HCQ serum level to assess non-adherence with a cut off of 106 ng/mL corresponding to 200 ng/ml in whole blood.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hydroxychloroquine-levels-in-patients-with-systemic-lupus-erythematosus-comparison-of-whole-blood-and-serum-levels/