Background: Using hydroxychloroquine (HCQ) dose of 5 mg/kg/day in systemic lupus erythematosus (SLE) is associated with a higher risk of flares; HCQ blood level monitoring could be a better way to adjust HCQ dose. We studied the upper threshold for a reference range of HCQ levels to inform routine monitoring.
Methods: This observational study included patients (n=2010) across the Systemic Lupus International Collaborating Clinics (SLICC), Wisconsin, International, and French studies, who underwent HCQ blood level measurements. Using adjusted spline and logistic regression analyses on the cross-sectional data, we first identified a HCQ blood level associated with higher HCQ toxicity. Next, we tested if this upper threshold level was supratherapeutic (no further risk reduction for SLE Disease Activity Index 2000 (SLEDAI-2K ≥6). Finally, we examined associations between chronic kidney disease (CKD) stage and supratherapeutic (toxic) HCQ blood levels.
Results: Among 1842 patients (excluding 168 patients with very low HCQ blood levels), 4.9% had HCQ related toxicity. Odds of toxicity were 2.1-fold higher with blood levels ≥1150 ng/mL, and 1.7-fold higher with cumulative HCQ dose per 1000g increase. Blood levels ≥1150 ng/mL were associated with a saturation in therapeutic effect, indicating supratherapeutic levels. Patients with CKD stage ≥3 had 2.3-fold higher odds of having supratherapeutic levels (≥1150 ng/mL).
Conclusion: The therapeutic reference range for HCQ blood level monitoring is 750-<1150 ng/ml. HCQ level monitoring could optimize HCQ use, particularly in patients with CKD stage ≥3. Future longitudinal studies are needed to validate the use of HCQ blood level monitoring in optimizing dosing.
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