Defining Optimally Safe and Effective Blood Levels of Hydroxychloroquine in Lupus: An Important Step toward Precision Drug Monitoring
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
Source: UNC Libraries
DOI: 10.17615/fs24-3656
Authors: Merrill, Joan T., Romero‐Diaz, Juanita, Chezel, Julie, Wallace, Daniel J., Gladman, Dafna D., Alarcón, Graciela S., Nguyen, Yann, Kalunian, Kenneth C., Mackay, Meggan, Jönsen, Andreas, Jacobsen, Søren, Petri, Michelle, Costedoat‐Chalumeau, Nathalie, Ginzler, Ellen M., Hanly, John G., Hollnagel, Fauzia, Ramsey‐Goldman, Rosalind, Fortin, Paul R., Peschken, Christine A., Rahman, Anisur, Clarke, Ann E., Van Vollenhoven, Ronald F., Garg, Shivani, Sanchez‐Guerrero, Jorge, Clarke, Ada, Kamen, Diane L., Urowitz, Murray B., Ruiz‐Irastorza, Guillermo, Aranow, Cynthia, Isenberg, David A., Gordon, Caroline, Lim, S. Sam, Bae, Sang‐Cheol, Puszkiel, Alicja, Buyon, Jill, Bernatsky, Sasha, Blanchet, Benoît, Le Guern, Véronique, Dooley, Mary Anne, Manzi, Susan, Bruce, Ian N., Inanc, Murat, Askanase, Anca
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7165389614