Evidence map›Paper›PMID 41367131›Full record

Observational studyArthritis & rheumatology (Hoboken, N.J.)2026

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

Shivani Garg, Benoît Blanchet, Yann Nguyen, Fauzia Hollnagel, Ada Clarke, Michelle Petri, Murray B Urowitz, John G Hanly, Caroline Gordon, Sang-Cheol Bae and 33 more

Abstract readObservational Study
In one paragraph

Observational study in Arthritis & rheumatology (Hoboken, N.J.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

43 authors.

Shivani GargUniversity of Wisconsin School of Medicine and Public Health, Madison.ORCID 0000-0001-7272-2692
Benoît BlanchetBiologie du Médicament-Toxicologie, Hôpital Cochin, Institut du Cancer Paris CARPEM, AP-HP Centre and Université de Paris, CNRS, INSERM, CiTCoM, U1268, Paris, France.
Yann NguyenNational Referral Centre for Rare Autoimmune and Systemic Diseases, Hôpital Cochin, AP-HP Centre and Université Paris Cité and Centre de Recherche en Epidémiologie et Statistiques, Unité Inserm 1153, Université de Paris Cité, Paris, France.ORCID 0000-0002-0866-3824
Fauzia HollnagelUniversity of Wisconsin School of Medicine and Public Health, Madison.
Ada ClarkeNational Referral Centre for Rare Autoimmune and Systemic Diseases, Hôpital Cochin, AP-HP Centre and Université Paris Cité and Centre de Recherche en Epidémiologie et Statistiques, Unité Inserm 1153, Université de Paris Cité, Paris, France.
Michelle PetriJohns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0003-1441-5373
Murray B UrowitzDivision of Rheumatology, University of Toronto and Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada.ORCID 0000-0001-7506-9166
John G HanlyQueen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada.ORCID 0000-0003-1029-9483
Caroline GordonDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.ORCID 0000-0002-1244-6443
Sang-Cheol BaeHanyang University Hospital for Rheumatic Diseases, Hanyang University Institute for Rheumatology, and Hanyang Institute of Bioscience and Biotechnology, Seoul, Korea.ORCID 0000-0003-4658-1093
Juanita Romero-DiazInstituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico.
Jorge Sanchez-GuerreroMount Sinai Hospital and University Health Network, University of Toronto, Toronto, Ontario, Canada.
Ann E ClarkeCumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Sasha BernatskyMcGill University Health Centre, Montreal, Quebec, Canada.ORCID 0000-0002-9515-2802
Daniel J WallaceUniversity of California, Los Angeles.
David A IsenbergUniversity College London, London, United Kingdom.ORCID 0000-0001-9514-2455
Anisur RahmanUniversity College London, London, United Kingdom.ORCID 0000-0003-2346-4484
Joan T MerrillOklahoma Medical Research Foundation, Oklahoma City.
Paul R FortinCentre ARThrite-UL, CHU de Québec-Université Laval, Quebec City, Quebec, Canada.
Dafna D GladmanDivision of Rheumatology, University of Toronto and Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada.ORCID 0000-0002-9074-0592
Ian N BruceCentre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Ellen M GinzlerState University of New York Downstate Medical Center, Brooklyn, New York City.
Mary Anne DooleyThurston Arthritis Research Center, University of North Carolina at Chapel Hill.
Rosalind Ramsey-GoldmanNorthwestern University Feinberg School of Medicine, Chicago, Illinois.ORCID 0000-0001-8712-787X
Susan ManziAllegheny Health Network, Pittsburgh, Pennsylvania.
Andreas JönsenLund University, Lund, Sweden.
Graciela S AlarcónUniversity of Alabama at Birmingham Marnix E. Heersink School of Medicine.ORCID 0000-0001-5190-9175
Ronald F Van VollenhovenUniversity of Amsterdam, Amsterdam, the Netherlands.
Cynthia AranowFeinstein Institute for Medical Research, Manhasset, New York.
Véronique Le GuernNational Referral Centre for Rare Autoimmune and Systemic Diseases, Hôpital Cochin, AP-HP Centre and Université Paris Cité and Centre de Recherche en Epidémiologie et Statistiques, Unité Inserm 1153, Université de Paris Cité, Paris, France.
Meggan MackayFeinstein Institute for Medical Research, Manhasset, New York.
Guillermo Ruiz-IrastorzaBiobizkaia Health Research Institute, University of the Basque Country, Barakaldo, Spain.
S Sam LimEmory University School of Medicine, Atlanta, Georgia.ORCID 0000-0003-2361-0787
Murat InancIstanbul University, Istanbul, Turkey.
Kenneth C KalunianUniversity of California San Diego School of Medicine, La Jolla.
Søren JacobsenRigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Christine A PeschkenUniversity of Manitoba, Winnipeg, Manitoba, Canada.
Diane L KamenMedical University of South Carolina, Charleston.
Anca AskanaseHospital for Joint Diseases and Seligman Centre for Advanced Therapeutics, New York University, New York City.ORCID 0000-0003-4597-5023
Jill BuyonNew York University School of Medicine, New York City.
Julie ChezelBichat University Hospital, AP-HP, Paris, France.
Alicja PuszkielBiologie du Médicament - Toxicologie, Cochin University Hospital, AP-HP and Université Paris Cité, INSERM, Optimisation thérapeutique en neuropharmacologie U1144, Paris, France.ORCID 0000-0003-2954-4418
Nathalie Costedoat-ChalumeauNational Referral Centre for Rare Autoimmune and Systemic Diseases, Hôpital Cochin, AP-HP Centre and Université Paris Cité and Centre de Recherche en Epidémiologie et Statistiques, Unité Inserm 1153, Université de Paris Cité, Paris, France.

Funding

Early and Personalized Cardiovascular Disease Preventive Care in Lupus Nephritis (EPiC-LN)K23AR084608 · NIAMS · YALE UNIVERSITY · PI SHIVANI GARG · 2024 to 2026
$512k
Lupus Foundation of AmericaNIAMS NIH HHS K23 AR084608NIH HHS 5K23AR084608-02Rheumatology Research Foundation
6 · The paper itself

Abstract

objectiveUsing 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.

methodsThis 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.

resultsAmong 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).

conclusionThe therapeutic reference range for HCQ blood level monitoring is 750 to <1,150 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.

Indexed as

Antirheumatic AgentsDrug MonitoringHydroxychloroquineLupus Erythematosus, SystemicAdultCross-Sectional StudiesFemaleHumansLogistic ModelsMaleMiddle AgedReference ValuesRenal Insufficiency, ChronicSeverity of Illness IndexAntirheumatic AgentsHydroxychloroquine

Identifiers

PMID41367131
PMCPMC13129619

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.