학술논문
Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence
Document Type
Academic Journal
Author
Blanchet, Benoit; Jallouli, Moez; Allard, Marie; Ghillani-Dalbin, Pascale; Galicier, Lionel; Aumaître, Olivier; Chasset, François; Le Guern, Véronique; Lioté, Frédéric; Smail, Amar; Limal, Nicolas; Perard, Laurent; Desmurs-Clavel, Hélène; Le Thi Huong, Du; Asli, Bouchra; Kahn, Jean-Emmanuel; Sailler, Laurent; Ackermann, Félix; Papo, Thomas; Sacré, Karim; Fain, Olivier; Stirnemann, Jérôme; Cacoub, Patrice; Leroux, Gaelle; Cohen-Bittan, Judith; Sellam, Jérémie; Mariette, Xavier; Goulvestre, Claire; Hulot, Jean Sébastien; Amoura, Zahir; Vidal, Michel; Piette, Jean-Charles; Astudillo, Leonardo; Belizna, Cristina; Belmatoug, Nadia; Benveniste, Olivier; Benyamine, Audrey; Bezanahary, Holly; Blanco, Patrick; Bodaghi, Bahram; Bourgeois, Pierre; Brihaye, Benoît; Chatelus, Emmanuel; Damade, Richard; Daugas, Eric; De Gennes, Christian; Delfraissy, Jean-François; Delluc, Céline; Delluc, Aurélien; Duhaut, Pierre; Dupuy, Alain; Durieu, Isabelle; Ea, Hang Korng; Farge, Dominique; Funck-Brentano, Christian; Gandjbakhch, Frédérique; Gellen-Dautremer, Justine; Godeau, Bertrand; Goujard, Cécile; Grandpeix, Catherine; Grange, Claire; Grimaldi, Lamiae; Guettrot-Imbert, Gaëlle; Guillevin, Loïc; Hachulla, Eric; Harle, Jean-Robert; Haroche, Julien; Hausfater, Pierre; Jouquan, Jean; Kaplanski, Gilles; Keshtmand, Homa; Khellaf, Mehdi; Lambotte, Olivier; Launay, David; Lechat, Philippe; Levesque, Hervé; Lidove, Olivier; Liozon, Eric; Ly, Kim; Mahevas, Matthieu; Mariampillai, Kubéraka; Mathian, Alexis; Mazodier, Karin; Michel, Marc; Morel, Nathalie; Mouthon, Luc; Musset, Lucile; Ngack, Rokiya; Ninet, Jacques; Oksenhendler, Eric; Pellegrin, Jean-Luc; Peyr, Olivier; Piette, Anne-Marie; Poindron, Vincent; Pourrat, Jacques; Roux, Fabienne; Saadoun, David; Sahali, Sabrinel; Saint-Marcoux, Bernadette; Sarrot-Reynauld, Françoise; Schoindre, Yoland; Sene, Damien; Serratrice, Jacques; Seve, Pascal; Sibilia, Jean; Simon, Claude; Sordet, Christelle; Terrier, Benjamin; Trad, Salim; Viallard, Jean-François; Vidal, Elisabeth; Wechsler, Bertrand; Weiller, Pierre-Jean
Source
Arthritis Research & Therapy. September 25, 2020, Vol. 22 Issue 1
Subject
Language
English
ISSN
1478-6354
Abstract
Author(s): Benoit Blanchet[sup.1,2], Moez Jallouli[sup.3], Marie Allard[sup.4,5], Pascale Ghillani-Dalbin[sup.6], Lionel Galicier[sup.7,8], Olivier Aumaître[sup.9,10], François Chasset[sup.11,12], Véronique Le Guern[sup.13], Frédéric Lioté[sup.14,15], Amar Smail[sup.16], Nicolas Limal[sup.17], Laurent Perard[sup.18], Hélène Desmurs-Clavel[sup.19], Du Le [...]
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 ([+ or -] SD) HCQ levels were 469 [+ or -] 223 ng/mL in serum and 916 [+ or -] 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 [+ or -] 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: Hydroxychloroquine, Systemic lupus erythematosus, Serum, Drug monitoring, Adherence
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 ([+ or -] SD) HCQ levels were 469 [+ or -] 223 ng/mL in serum and 916 [+ or -] 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 [+ or -] 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: Hydroxychloroquine, Systemic lupus erythematosus, Serum, Drug monitoring, Adherence