Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence
Benoı̂t Blanchet, M. Jallouli, Marie Allard, Pascale Ghillani‐Dalbin, Lionel Galicier, O. Aumaître, François Chasset, Véronique Le Guern, Frédéric Lioté, Amar Smaïl, Nicolas Limal, Laurent Pérard, H. Desmurs‐Clavel, D. Lê Thi Huong, Bouchra Asli, Jean‐Emmanuel Kahn, L. Sailler, Félix Ackermann, T. Papo, Karim Sacré, Olivier Fain, Jérôme Stirnemann, P. Cacoub, Gaëlle Leroux, Judith Cohen‐Bittan, Jérémie Sellam, Xavier Mariette, Claire Goulvestre, Jean‐Sébastien Hulot, Zahir Amoura, Michel Vidal, Jean‐Charles Piette, on behalf of the PLUS Group, Leonardo Astudillo, C. Bélizna, Nadia Belmatoug, Olivier Benvéniste, A. Benyamine, Holly Bezanahary, Patrick Blanco, Bahram Bodaghi, Pierre Bourgeois, B. Brihaye, Emmanuel Chatelus, R. Damade, Éric Daugas, C. De Gennes, Jean‐François Delfraissy, C. Delluc, Aurélien Delluc, P. Duhaut, Alain Dupuy, I. Durieu, Hang‐Korng Ea, Dominique Farge, Christian Funck‐Brentano, Frédérique Gandjbakhch, Justine Gellen‐Dautremer, Bertrand Godeau, Cécile Goujard, C. Grandpeix, C. Grangé, Lamiae Grimaldi‐Bensouda, G. Guettrot-Imbert, Loïc Guillevin, É. Hachulla, Jean‐Robert Harlé, Julien Haroche, Pierre Hausfater, Jean Jouquan, Gilles Kaplanski, Homa Keshtmand, Mehdi Khellaf, Olivier Lambotte, David Launay, Philippe Lechat, H. Lévesque, Olivier Lidove, Eric Liozon, K.H. Ly, Matthieu Mahevas, K. Mariampillai, Alexis Mathian, K. Mazodier, Marc Michel, Nathalie Morel, Luc Mouthon, Lucile Musset, Rokiya Ngack, J. Ninet, Éric Oksenhendler, Jean‐Luc Pellegrin, Olivier Peyr, Anne‐Marie Piette, Vincent Poindron, Jacques Pourrat, Fabienne Roux, David Saadoun, Sabrinel Sahali, B. Saint-Marcoux
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.