Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study)
Authors: Nathalie Costedoat-Chalumeau, Lionel Galicier, Olivier Aumaître, Camille Francès, Véronique Le Guern, Frédéric Lioté, Amar Smail, Nicolas Limal, Laurent Perard, Hélène Desmurs-Clavel, Du Le Thi Huong Boutin, Bouchra Asli, Jean-Emmanuel Kahn, Jacques Pourrat, Laurent Sailler, Félix Ackermann, Thomas Papo, Karim Sacré, Olivier Fain, Jerome Stirnemann, Patrice Cacoub, Moez Jallouli, Gaelle Leroux, Judith Cohen-Bittan, Marie-Laure Tanguy, Jean-Sébastien Hulot, Philippe Lechat, Lucile Musset, Zahir Amoura, Jean-Charles Piette, Leonardo Astudillo, Cristina Belizna, Nadia Belmatoug, Olivier Benveniste, Audrey Benyamine, Holly Bezanahary, Patrick Blanco, Olivier Bletry, 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, EA Hang-Korng, Dominique Farge, Christian Funck-Brentano, Frédérique Gandjbakhch, Justine Gellen-Dautremer, Pascale Ghillani-Dalbin, 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, Hervé Levesque, Olivier Lidove, Eric Liozon, LY Kim, Matthieu Mahevas, Kubéraka Mariampillai, Xavier Mariette, Alexis Mathian, Karin Mazodier, Marc Michel, Nathalie Morel, Luc Mouthon, Rokiya Ngack, Jacques Ninet, Eric Oksenhendler, Jean-Luc Pellegrin, Olivier Peyr, Anne-Marie Piette, Vincent Poindron, Fabienne Roux, David Saadoun, Sabrinel Sahali, Bernadette Saint-Marcoux, Françoise Sarrot-Reynauld, Yoland Schoindre, Jérémie Sellam, 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, Noël Zahr
Journal: Annals of the Rheumatic Diseases (2012)

Hydroxychloroquine (HCQ) is an important medication for treating systemic lupus erythematosus (SLE). Its blood concentration ([HCQ]) varies widely between patients and is a marker and predictor of SLE flares. This prospective randomised, double-blind, placebo-controlled, multicentre study sought to compare standard and adjusted HCQ dosing schedules that target [HCQ] ≥1000 ng/ml to reduce SLE flares. [HCQ] was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6 months. Patients with [HCQ] from 100 to 750 ng/ml were randomised to one of two treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve the target [HCQ] (group 2). The primary end point was the number of patients with flares during 7 months of follow-up. Overall, mean [HCQ] was 918±451 ng/ml. Active SLE was less prevalent in patients with higher [HCQ]. A total of 171 patients were randomised and followed for 7 months. SLE flare rates were similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a significant spontaneous increase in [HCQ] in both groups between inclusion and randomisation strongly suggested improved treatment adherence. Patients at the therapeutic target throughout follow-up tended to have fewer flares than those with low [HCQ] (20.5% vs 35.1%, p=0.12). Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up.