. 2020 Sep 25;22(1):223.

doi: 10.1186/s13075-020-02291-z.

Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence

Benoit Blanchet^{1

2}, Moez Jallouli³, Marie Allard^{4

5}, Pascale Ghillani-Dalbin⁶, Lionel Galicier^{7

8}, Olivier Aumaître^{9

10}, François Chasset^{11

12}, Véronique Le Guern¹³, Frédéric Lioté^{14

15}, Amar Smail¹⁶, Nicolas Limal¹⁷, Laurent Perard¹⁸, Hélène Desmurs-Clavel¹⁹, Du Le Thi Huong^{11

20}, Bouchra Asli^{7

8}, Jean-Emmanuel Kahn²¹, Laurent Sailler^{22

23}, Félix Ackermann²⁴, Thomas Papo^{4

5}, Karim Sacré^{4

5}, Olivier Fain²⁵, Jérôme Stirnemann²⁶, Patrice Cacoub^{11

27}, Gaelle Leroux^{11

27}, Judith Cohen-Bittan²⁸, Jérémie Sellam²⁹, Xavier Mariette³⁰, Claire Goulvestre³¹, Jean Sébastien Hulot³², Zahir Amoura^{11

20}, Michel Vidal^{1

2}, Jean-Charles Piette^{11

27}; PLUS Group; Noémie Jourde-Chiche³³, Nathalie Costedoat-Chalumeau^{34

35

36}

Collaborators, Affiliations

Collaborators

PLUS Group:
Leonardo Astudillo, Cristina Belizna, Nadia Belmatoug, Olivier Benveniste, Audrey Benyamine, Holly Bezanahary, Patrick Blanco, Bahram Bodaghi, Pierre Bourgeois, Benoît Brihaye, Emmanuel Chatelus, Richard Damade, Eric Daugas, Christian De Gennes, Jean-François Delfraissy, Céline Delluc, Aurélien Delluc, Pierre Duhaut, Alain Dupuy, Isabelle Durieu, Hang Korng Ea, Dominique Farge, Christian Funck-Brentano, Frédérique Gandjbakhch, Justine Gellen-Dautremer, Bertrand Godeau, Cécile Goujard, Catherine Grandpeix, Claire Grange, Lamiae Grimaldi, Gaëlle Guettrot-Imbert, Loïc Guillevin, Eric Hachulla, Jean-Robert Harle, Julien Haroche, Pierre Hausfater, Jean Jouquan, Gilles Kaplanski, Homa Keshtmand, Mehdi Khellaf, Olivier Lambotte, David Launay, Philippe Lechat, Hervé Levesque, Olivier Lidove, Eric Liozon, Kim Ly, Matthieu Mahevas, Kubéraka Mariampillai, Alexis Mathian, Karin Mazodier, Marc Michel, Nathalie Morel, Luc Mouthon, Lucile Musset, Rokiya Ngack, Jacques Ninet, Eric Oksenhendler, Jean-Luc Pellegrin, Olivier Peyr, Anne-Marie Piette, Vincent Poindron, Jacques Pourrat, Fabienne Roux, David Saadoun, Sabrinel Sahali, Bernadette Saint-Marcoux, Françoise Sarrot-Reynauld, Yoland Schoindre, Damien Sene, Jacques Serratrice, Pascal Seve, Jean Sibilia, Claude Simon, Christelle Sordet, Benjamin Terrier, Salim Trad, Jean-François Viallard, Elisabeth Vidal, Bertrand Wechsler, Pierre-Jean Weiller

Affiliations

¹ AP-HP, Hôpital Cochin, Biologie du médicament - Toxicologie, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.
² UMR8038 CNRS, U1268 INSERM, Faculty of Pharmacy, University Paris Descartes, PRES Sorbonne Paris Cité, Paris, France.
³ Service de Médecine interne, Hôpital Hédi Chaker, Sfax, Tunisie.
⁴ Université Paris-Diderot, Sorbonne Paris-Cité, F-75205, Paris, France.
⁵ AP-HP, Hôpital Bichat Claude-Bernard, service de médecine interne, 46 rue Henri-Huchard, 75018, Paris, France.
⁶ AP-HP, Hôpital Pitié-Salpêtrière, Département d'immunologie, 47-83 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
⁷ Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
⁸ AP-HP, Hôpital Saint Louis, service d'immunologie clinique, 1 avenue Claude Vellefaux, 75010, Paris, France.
⁹ Université de Clermont-Ferrand, 63003, Clermont-Ferrand, France.
¹⁰ CHU Clermont-Ferrand, Hôpital Gabriel Montpied, service de médecine interne, 58 rue Montalembert, 63003, Clermont-Ferrand cedex1, France.
¹¹ UPMC, Université Paris 6, Paris, France.
¹² AP-HP, Hôpital Tenon, service de dermatologie allergologie, 4 rue de la Chine, 75020, Paris, France.
¹³ AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.
¹⁴ Université de Paris, F-75205, Paris, France.
¹⁵ AP-HP, Hôpital Lariboisière, service de rhumatologie, DMU Locomotion, 2 rue Ambroise Paré, 75010, Paris, France.
¹⁶ CHU Amiens, Hôpital Nord, service de médecine interne, Place Victor Pauchet, 80000, Amiens, France.
¹⁷ AP-HP, Hôpital Henri Mondor, service de médecine interne, 51 avenue du Maréchal de Tassigny, 94000, Créteil, France.
¹⁸ Centre Hospitalier Saint Joseph Saint Luc, service de médecine interne, 20 quai Claude Bernard, 69007, Lyon, France.
¹⁹ Hospices Civils de Lyon, Groupement Hospitalier Edouard Herriot, service de médecine interne, 5 place d'Arsonval, 69003, Lyon, France.
²⁰ AP-HP, Hôpital Pitié-Salpêtrière, Centre de référence pour le Lupus Systémique et le syndrome des Antiphospholipides, service de médecine interne, 47-83 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
²¹ Servie de Médecine Interne, Hôpital Ambroise Paré, Université Paris Saclay, 9 Avenue Charles de Gaulle, 92104, Boulogne-Billancourt, France.
²² Université Paul-Sabatier, Toulouse, France.
²³ CHU Toulouse, Hôpital Purpan, Service de Médecine Interne, Place Dr Baylac, F-31059, Toulouse, France.
²⁴ Hôpital Foch, Service de médecine interne, 92150, Suresnes, France.
²⁵ Sorbonne Université, Hôpital Saint Antoine, APHP, service de médecine interne, F 75012, Paris, France.
²⁶ Hôpitaux Universitaires de Genève, Service de Médecine interne Générale, Avenue Gabrielle Perret Gentil 4, CH-1211, Geneva, Switzerland.
²⁷ AP-HP, Hôpital Pitié-Salpêtrière, Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne 2, 47-83 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
²⁸ AP-HP, Hôpital Pitié-Salpêtrière, service de gériatrie, 47-83 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
²⁹ AP-HP, Hôpital Saint Antoine, Service de Rhumatologie, 184 Rue du Faubourg Saint-Antoine, 75012, Paris, France.
³⁰ Service de Rhumatologie, Hôpitaux Universitaires Paris-Sud, AP-HP, Université Paris-Sud, INSERM UMR 1184, Paris, France.
³¹ AP-HP, Hôpital Cochin, service d'immunologie biologique, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.
³² INSERM, UMRS 970, Paris Cardiovascular Research Center, Paris, France.
³³ Aix-Marseille Univ, C2VN, INSERM 1263, INRA 1260 ; AP-HM, Centre de Néphrologie et Transplantation Rénale, Marseille, France.
³⁴ AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France. nathalie.costedoat@gmail.com.
³⁵ Université Paris-Descartes, Paris, France. nathalie.costedoat@gmail.com.
³⁶ INSERM U 1153, Center for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France. nathalie.costedoat@gmail.com.

PMID: 32977856
PMCID: PMC7517694
DOI: 10.1186/s13075-020-02291-z

Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence

Benoit Blanchet et al. Arthritis Res Ther. 2020.

. 2020 Sep 25;22(1):223.

doi: 10.1186/s13075-020-02291-z.

Authors

Collaborators

PLUS Group:
Leonardo Astudillo, Cristina Belizna, Nadia Belmatoug, Olivier Benveniste, Audrey Benyamine, Holly Bezanahary, Patrick Blanco, Bahram Bodaghi, Pierre Bourgeois, Benoît Brihaye, Emmanuel Chatelus, Richard Damade, Eric Daugas, Christian De Gennes, Jean-François Delfraissy, Céline Delluc, Aurélien Delluc, Pierre Duhaut, Alain Dupuy, Isabelle Durieu, Hang Korng Ea, Dominique Farge, Christian Funck-Brentano, Frédérique Gandjbakhch, Justine Gellen-Dautremer, Bertrand Godeau, Cécile Goujard, Catherine Grandpeix, Claire Grange, Lamiae Grimaldi, Gaëlle Guettrot-Imbert, Loïc Guillevin, Eric Hachulla, Jean-Robert Harle, Julien Haroche, Pierre Hausfater, Jean Jouquan, Gilles Kaplanski, Homa Keshtmand, Mehdi Khellaf, Olivier Lambotte, David Launay, Philippe Lechat, Hervé Levesque, Olivier Lidove, Eric Liozon, Kim Ly, Matthieu Mahevas, Kubéraka Mariampillai, Alexis Mathian, Karin Mazodier, Marc Michel, Nathalie Morel, Luc Mouthon, Lucile Musset, Rokiya Ngack, Jacques Ninet, Eric Oksenhendler, Jean-Luc Pellegrin, Olivier Peyr, Anne-Marie Piette, Vincent Poindron, Jacques Pourrat, Fabienne Roux, David Saadoun, Sabrinel Sahali, Bernadette Saint-Marcoux, Françoise Sarrot-Reynauld, Yoland Schoindre, Damien Sene, Jacques Serratrice, Pascal Seve, Jean Sibilia, Claude Simon, Christelle Sordet, Benjamin Terrier, Salim Trad, Jean-François Viallard, Elisabeth Vidal, Bertrand Wechsler, Pierre-Jean Weiller

Affiliations

¹ AP-HP, Hôpital Cochin, Biologie du médicament - Toxicologie, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.
² UMR8038 CNRS, U1268 INSERM, Faculty of Pharmacy, University Paris Descartes, PRES Sorbonne Paris Cité, Paris, France.
³ Service de Médecine interne, Hôpital Hédi Chaker, Sfax, Tunisie.
⁴ Université Paris-Diderot, Sorbonne Paris-Cité, F-75205, Paris, France.
⁵ AP-HP, Hôpital Bichat Claude-Bernard, service de médecine interne, 46 rue Henri-Huchard, 75018, Paris, France.
⁶ AP-HP, Hôpital Pitié-Salpêtrière, Département d'immunologie, 47-83 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
⁷ Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
⁸ AP-HP, Hôpital Saint Louis, service d'immunologie clinique, 1 avenue Claude Vellefaux, 75010, Paris, France.
⁹ Université de Clermont-Ferrand, 63003, Clermont-Ferrand, France.
¹⁰ CHU Clermont-Ferrand, Hôpital Gabriel Montpied, service de médecine interne, 58 rue Montalembert, 63003, Clermont-Ferrand cedex1, France.
¹¹ UPMC, Université Paris 6, Paris, France.
¹² AP-HP, Hôpital Tenon, service de dermatologie allergologie, 4 rue de la Chine, 75020, Paris, France.
¹³ AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.
¹⁴ Université de Paris, F-75205, Paris, France.
¹⁵ AP-HP, Hôpital Lariboisière, service de rhumatologie, DMU Locomotion, 2 rue Ambroise Paré, 75010, Paris, France.
¹⁶ CHU Amiens, Hôpital Nord, service de médecine interne, Place Victor Pauchet, 80000, Amiens, France.
¹⁷ AP-HP, Hôpital Henri Mondor, service de médecine interne, 51 avenue du Maréchal de Tassigny, 94000, Créteil, France.
¹⁸ Centre Hospitalier Saint Joseph Saint Luc, service de médecine interne, 20 quai Claude Bernard, 69007, Lyon, France.
¹⁹ Hospices Civils de Lyon, Groupement Hospitalier Edouard Herriot, service de médecine interne, 5 place d'Arsonval, 69003, Lyon, France.
²⁰ AP-HP, Hôpital Pitié-Salpêtrière, Centre de référence pour le Lupus Systémique et le syndrome des Antiphospholipides, service de médecine interne, 47-83 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
²¹ Servie de Médecine Interne, Hôpital Ambroise Paré, Université Paris Saclay, 9 Avenue Charles de Gaulle, 92104, Boulogne-Billancourt, France.
²² Université Paul-Sabatier, Toulouse, France.
²³ CHU Toulouse, Hôpital Purpan, Service de Médecine Interne, Place Dr Baylac, F-31059, Toulouse, France.
²⁴ Hôpital Foch, Service de médecine interne, 92150, Suresnes, France.
²⁵ Sorbonne Université, Hôpital Saint Antoine, APHP, service de médecine interne, F 75012, Paris, France.
²⁶ Hôpitaux Universitaires de Genève, Service de Médecine interne Générale, Avenue Gabrielle Perret Gentil 4, CH-1211, Geneva, Switzerland.
²⁷ AP-HP, Hôpital Pitié-Salpêtrière, Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne 2, 47-83 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
²⁸ AP-HP, Hôpital Pitié-Salpêtrière, service de gériatrie, 47-83 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
²⁹ AP-HP, Hôpital Saint Antoine, Service de Rhumatologie, 184 Rue du Faubourg Saint-Antoine, 75012, Paris, France.
³⁰ Service de Rhumatologie, Hôpitaux Universitaires Paris-Sud, AP-HP, Université Paris-Sud, INSERM UMR 1184, Paris, France.
³¹ AP-HP, Hôpital Cochin, service d'immunologie biologique, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.
³² INSERM, UMRS 970, Paris Cardiovascular Research Center, Paris, France.
³³ Aix-Marseille Univ, C2VN, INSERM 1263, INRA 1260 ; AP-HM, Centre de Néphrologie et Transplantation Rénale, Marseille, France.
³⁴ AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France. nathalie.costedoat@gmail.com.
³⁵ Université Paris-Descartes, Paris, France. nathalie.costedoat@gmail.com.
³⁶ INSERM U 1153, Center for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France. nathalie.costedoat@gmail.com.

PMID: 32977856
PMCID: PMC7517694
DOI: 10.1186/s13075-020-02291-z

Abstract

Background: Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients.

Methods: HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ < 200 ng/mL.

Results: The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76-0.94) and specificity of 0.89 (95% CI 0.72-0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level (< 20 ng/mL) were also undetectable (< 20 ng/mL).

Conclusions: These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.

Keywords: Adherence; Drug monitoring; Hydroxychloroquine; Serum; Systemic lupus erythematosus.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 2**
Serum and whole-blood levels of hydroxychloroquine (HCQ), desethylchloroquine (DCQ), and composite (HCQ+DCQ) in log scale

**Fig. 3**
Correlation between serum and whole-blood levels of hydroxychloroquine (HCQ), desethylchloroquine (DCQ), and composite (HCQ+DCQ)

**Fig. 4**
Relation between serum and whole-blood level of hydroxychloroquine (HCQ) in SLE patients with whole-blood levels < 300 ng/mL. The green and violet lines represent the HCQ level cut-off for non-adherence in serum (106 ng/mL) and whole blood (200 ng/mL), respectively. The orange square represents 14 patients who had both serum and whole-blood HCQ levels below the lower limit of quantification (20 ng/mL). Red crosses represent severe non-adherent patients with whole-blood HCQ levels between 20 and 200 ng/mL. Blue crosses represent patients with whole-blood HCQ levels between 200 and 300 ng/mL

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Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence

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Affiliations

Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence

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