Journal article
Defining Optimally Safe and Effective Blood Levels of Hydroxychloroquine in Lupus: An Important Step toward Precision Drug Monitoring
Arthritis & rheumatology (Hoboken, N.J.)
09 Dec 2025
PMID: 41367131
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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.
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).
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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Details
- Title
- Defining Optimally Safe and Effective Blood Levels of Hydroxychloroquine in Lupus: An Important Step toward Precision Drug Monitoring
- Creators
- Shivani Garg - University of Wisconsin–MadisonBenoît Blanchet - Hôpital CochinYann Nguyen - Centre de Recherche Épidémiologie et StatistiqueFauzia Hollnagel - University of Wisconsin School of Medicine and Public HealthAda Clarke - Centre de Recherche Épidémiologie et StatistiqueMichelle Petri - Johns Hopkins MedicineMurray B Urowitz - Krembil Research InstituteJohn G Hanly - Dalhousie UniversityCaroline Gordon - University of BirminghamSang-Cheol Bae - Hanyang University Seoul HospitalJuanita Romero-Diaz - Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránJorge Sanchez-Guerrero - University of TorontoAnn E Clarke - University of CalgarySasha Bernatsky - McGill University Health CentreDaniel J Wallace - University of California, Los AngelesDavid A Isenberg - University College LondonAnisur Rahman - University College LondonJoan T Merrill - Oklahoma Medical Research FoundationPaul R Fortin - Université LavalDafna D Gladman - Krembil Research InstituteIan N Bruce - Manchester Academic Health Science CentreEllen M Ginzler - SUNY Downstate Health Sciences UniversityMary Anne Dooley - University of North Carolina at Chapel HillRosalind Ramsey-Goldman - Northwestern UniversitySusan Manzi - Allegheny Health NetworkAndreas Jönsen - Lund UniversityGraciela S Alarcón - University of Alabama at BirminghamRonald F Van Vollenhoven - University of AmsterdamCynthia Aranow - Feinstein Institute for Medical ResearchVéronique Le Guern - Université Paris CitéMeggan Mackay - Centre de Recherche Épidémiologie et StatistiqueGuillermo Ruiz-Irastorza - University of the Basque CountryS Sam Lim - Emory UniversityMurat Inanc - Istanbul UniversityKenneth C Kalunian - University of California San DiegoSøren Jacobsen - RigshospitaletChristine A Peschken - University of ManitobaDiane L Kamen - Medical University of South CarolinaAnca Askanase - New York University Langone Orthopedic HospitalJill Buyon - New York UniversityJulie Chezel - Hôpital Bichat-Claude-BernardAlicja Puszkiel - Assistance Publique – Hôpitaux de ParisNathalie Costedoat-Chalumeau - Centre de Recherche Épidémiologie et Statistique
- Publication Details
- Arthritis & rheumatology (Hoboken, N.J.)
- Publisher
- WILEY; HOBOKEN
- Number of pages
- 12
- Grant note
- Lupus Foundation of America, Wisconsin Chapter, Research AwardRheumatology Research Foundation Innovation Research AwardNIH: 5K23-AR-084608-02 Lupus UK, SandWest Birmingham Hospitals NHS TrustNIHR/Wellcome Trust Birmingham Clinical Research FacilityBasic Science Research Program through the National Research Foundation of Korea - Ministry of Education: NRF-2021R1A6A1A03038899 NIHR Manchester Biomedical Research Centre: NIHR203308
Supported by a grant sponsored by the Lupus Foundation of America, Wisconsin Chapter, Research Award, and the Rheumatology Research Foundation Innovation Research Award. Dr Garg's work was supported by the NIH (grant 5K23-AR-084608-02). The content is solely the responsibility of authors and does not necessarily represent the official views of the fundersor the NIH. Dr Gordon's work was supported by Lupus UK, Sand well and West Birmingham Hospitals NHS Trust, and the NIHR/Wellcome Trust Birmingham Clinical Research Facility. Dr Bae's work was supported in part by the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education (NRF-2021R1A6A1A03038899).Dr Bruce is an NIHR Senior Investigator, and his work was supported by the NIHR Manchester Biomedical Research Centre (NIHR203308)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:001693047200001
- Scopus ID
- 2-s2.0-105030477915
- Other Identifier
- 991022146942604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Rheumatology