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; Juanita Romero-Diaz; Jorge Sanchez-Guerrero; Ann E Clarke; Sasha Bernatsky; Daniel J Wallace; David A 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 F Van Vollenhoven; Cynthia Aranow; Véronique Le Guern; Meggan Mackay; Guillermo Ruiz-Irastorza; S Sam Lim; Murat Inanc; Kenneth C Kalunian; Søren Jacobsen; Christine A Peschken; Diane L Kamen; Anca Askanase; Jill Buyon; Julie Chezel; Alicja Puszkiel; Nathalie Costedoat-Chalumeau

doi:10.1002/art.70010

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, Juanita Romero-Diaz, Jorge Sanchez-Guerrero, Ann E Clarke, Sasha Bernatsky, Daniel J Wallace, David A Isenberg, Anisur Rahman, Joan T Merrill, Paul R Fortin, Dafna D GladmanIan N Bruce, Ellen M Ginzler, Mary Anne Dooley, Rosalind Ramsey-Goldman, Susan Manzi, Andreas Jönsen, Graciela S Alarcón, Ronald F Van Vollenhoven, Cynthia Aranow, Véronique Le Guern, Meggan Mackay, Guillermo Ruiz-Irastorza, S Sam Lim, Murat Inanc, Kenneth C Kalunian, Søren Jacobsen, Christine A Peschken, Diane L Kamen, Anca Askanase, Jill Buyon, Julie Chezel, Alicja Puszkiel, Nathalie Costedoat-Chalumeau

^*Corresponding author af dette arbejde

Afdeling for Rygkirurgi, Led- og Bindevævssygdomme HOC

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.

Originalsprog	Engelsk
Tidsskrift	Arthritis and Rheumatology
ISSN	2326-5191
DOI	https://doi.org/10.1002/art.70010
Status	E-pub ahead of print - 9 dec. 2025

Adgang til dokumentet

10.1002/art.70010Licens: CC BY

Citationsformater

Garg, S., Blanchet, B., Nguyen, Y., Hollnagel, F., Clarke, A., Petri, M., Urowitz, M. B., Hanly, J. G., Gordon, C., Bae, S.-C., Romero-Diaz, J., Sanchez-Guerrero, J., Clarke, A. E., Bernatsky, S., Wallace, D. J., Isenberg, D. A., Rahman, A., Merrill, J. T., Fortin, P. R., ... Costedoat-Chalumeau, N. (2025). Defining Optimally Safe and Effective Blood Levels of Hydroxychloroquine in Lupus: An Important Step toward Precision Drug Monitoring. Arthritis and Rheumatology. Advance online publication. https://doi.org/10.1002/art.70010

Garg, S, Blanchet, B, Nguyen, Y, Hollnagel, F, Clarke, A, Petri, M, Urowitz, MB, Hanly, JG, Gordon, C, Bae, S-C, Romero-Diaz, J, Sanchez-Guerrero, J, Clarke, AE, Bernatsky, S, Wallace, DJ, Isenberg, DA, Rahman, A, Merrill, JT, Fortin, PR, Gladman, DD, Bruce, IN, Ginzler, EM, Dooley, MA, Ramsey-Goldman, R, Manzi, S, Jönsen, A, Alarcón, GS, Van Vollenhoven, RF, Aranow, C, Le Guern, V, Mackay, M, Ruiz-Irastorza, G, Lim, SS, Inanc, M, Kalunian, KC, Jacobsen, S, Peschken, CA, Kamen, DL, Askanase, A, Buyon, J, Chezel, J, Puszkiel, A & Costedoat-Chalumeau, N 2025, 'Defining Optimally Safe and Effective Blood Levels of Hydroxychloroquine in Lupus: An Important Step toward Precision Drug Monitoring', Arthritis and Rheumatology. https://doi.org/10.1002/art.70010

@article{9579a8ad3a0a479584012472e94db8ad,

title = "Defining Optimally Safe and Effective Blood Levels of Hydroxychloroquine in Lupus: An Important Step toward Precision Drug Monitoring",

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.",

author = "Shivani Garg and Beno{\^i}t Blanchet and Yann Nguyen and Fauzia Hollnagel and Ada Clarke and Michelle Petri and Urowitz, {Murray B} and Hanly, {John G} and Caroline Gordon and Sang-Cheol Bae and Juanita Romero-Diaz and Jorge Sanchez-Guerrero and Clarke, {Ann E} and Sasha Bernatsky and Wallace, {Daniel J} and Isenberg, {David A} and Anisur Rahman and Merrill, {Joan T} and Fortin, {Paul R} and Gladman, {Dafna D} and Bruce, {Ian N} and Ginzler, {Ellen M} and Dooley, {Mary Anne} and Rosalind Ramsey-Goldman and Susan Manzi and Andreas J{\"o}nsen and Alarc{\'o}n, {Graciela S} and {Van Vollenhoven}, {Ronald F} and Cynthia Aranow and {Le Guern}, V{\'e}ronique and Meggan Mackay and Guillermo Ruiz-Irastorza and Lim, {S Sam} and Murat Inanc and Kalunian, {Kenneth C} and S{\o}ren Jacobsen and Peschken, {Christine A} and Kamen, {Diane L} and Anca Askanase and Jill Buyon and Julie Chezel and Alicja Puszkiel and Nathalie Costedoat-Chalumeau",

year = "2025",

month = dec,

day = "9",

doi = "10.1002/art.70010",

language = "English",

journal = "Arthritis and Rheumatology",

issn = "2326-5191",

publisher = "John Wiley and Sons Ltd",

}

TY - JOUR

T1 - Defining Optimally Safe and Effective Blood Levels of Hydroxychloroquine in Lupus

T2 - An Important Step toward Precision Drug Monitoring

AU - Garg, Shivani

AU - Blanchet, Benoît

AU - Nguyen, Yann

AU - Hollnagel, Fauzia

AU - Clarke, Ada

AU - Petri, Michelle

AU - Urowitz, Murray B

AU - Hanly, John G

AU - Gordon, Caroline

AU - Bae, Sang-Cheol

AU - Romero-Diaz, Juanita

AU - Sanchez-Guerrero, Jorge

AU - Clarke, Ann E

AU - Bernatsky, Sasha

AU - Wallace, Daniel J

AU - Isenberg, David A

AU - Rahman, Anisur

AU - Merrill, Joan T

AU - Fortin, Paul R

AU - Gladman, Dafna D

AU - Bruce, Ian N

AU - Ginzler, Ellen M

AU - Dooley, Mary Anne

AU - Ramsey-Goldman, Rosalind

AU - Manzi, Susan

AU - Jönsen, Andreas

AU - Alarcón, Graciela S

AU - Van Vollenhoven, Ronald F

AU - Aranow, Cynthia

AU - Le Guern, Véronique

AU - Mackay, Meggan

AU - Ruiz-Irastorza, Guillermo

AU - Lim, S Sam

AU - Inanc, Murat

AU - Kalunian, Kenneth C

AU - Jacobsen, Søren

AU - Peschken, Christine A

AU - Kamen, Diane L

AU - Askanase, Anca

AU - Buyon, Jill

AU - Chezel, Julie

AU - Puszkiel, Alicja

AU - Costedoat-Chalumeau, Nathalie

PY - 2025/12/9

Y1 - 2025/12/9

N2 - 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.

AB - 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.

U2 - 10.1002/art.70010

DO - 10.1002/art.70010

M3 - Journal article

C2 - 41367131

SN - 2326-5191

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

ER -

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

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater