Defining Optimally Safe and Effective Blood Levels of Hydroxychloroquine in Lupus: An Important Step Toward Precision Drug Monitoring

作者：Shivani Garg, Benoı̂t Blanchet, Yann Nguyen, Fauzia Hollnagel, Ada Clarke, Michelle Petri, Murray B. Urowitz, John G. Hanly, Caroline Gordon, Sang‐Cheol Bae, Juanita Romero‐Díaz, Jorge Sánchez‐Guerrero, Ann E. Clarke, Sasha Bernatsky, Daniel J. Wallace, David Isenberg, Anisur Rahman, Joan T. Merrill, Paul R. Fortin, Dafna D. Gladman, Ian N Bruce, Ellen M. Ginzler, Mary Anne Dooley, Rosalind Ramsey‐Goldman, Susan Manzi, Andreas Jönsen, Graciela S. Alarcón, Ronald van Vollenhoven, Cynthia Aranow, Véronique Le Guern, Meggan Mackay, Guillermo Ruiz‐Irastorza, S. Sam Lim, Murat İnanç, Kenneth Kalunian, Søren Jacobsen, Christine Peschken, Diane L. Kamen, Anca Askanase, Jill P. Buyon, J. Chezel, Alicja Puszkiel, N. Costedoat‐Chalumeau · 发表于：Arthritis & Rheumatology · 年份：2025 · DOI：10.1002/art.70010 · 被引用次数：6 · 研究领域：Systemic Lupus Erythematosus Research、Drug-Induced Ocular Toxicity、Blood Pressure and Hypertension Studies

OBJECTIVE: Using a 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 the 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 = 2,010) across the Systemic Lupus International Collaborating Clinics, 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 an HCQ blood level associated with higher HCQ toxicity. Next, we tested if this upper threshold level was supratherapeutic (no further risk reduction for the Systemic Lupus Erythematosus Disease Activity Index 2000 [score ≥6]). Finally, we examined associations between chronic kidney disease (CKD) stage and supratherapeutic (toxic) HCQ blood levels. RESULTS: Among 1,842 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 ≥1,150 ng/mL and 1.7-fold higher with the cumulative HCQ dose per 1,000-g increase. Blood levels ≥1,150 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 (≥1,150 ng/mL). CONCLUSION: The therapeutic refer...