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Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study)
  1. Nathalie Costedoat-Chalumeau1,2,
  2. Lionel Galicier3,4,
  3. Olivier Aumaître5,6,
  4. Camille Francès7,8,
  5. Véronique Le Guern9,10,
  6. Frédéric Lioté11,12,
  7. Amar Smail13,
  8. Nicolas Limal14,
  9. Laurent Perard15,
  10. Hélène Desmurs-Clavel15,
  11. Du Le Thi Huong Boutin2,
  12. Bouchra Asli4,
  13. Jean-Emmanuel Kahn16,
  14. Jacques Pourrat17,18,
  15. Laurent Sailler17,19,
  16. Félix Ackermann16,
  17. Thomas Papo20,21,
  18. Karim Sacré20,21,
  19. Olivier Fain22,23,
  20. Jerome Stirnemann22,23,
  21. Patrice Cacoub1,2,24,25,
  22. Moez Jallouli2,
  23. Gaelle Leroux2,
  24. Judith Cohen-Bittan2,
  25. Marie-Laure Tanguy26,
  26. Jean-Sébastien Hulot1,27,
  27. Philippe Lechat1,27,
  28. Lucile Musset28,
  29. Zahir Amoura1,2,
  30. Jean-Charles Piette1,2,
  31. on behalf of Group PLUS
  1. 1UPMC, Université Paris 6, Paris, France
  2. 2AP-HP, Centre de référence National Pour le Lupus Systémique et le syndrome des Antiphospholipides, service de médecine interne, Hôpital Pitié-Salpêtrière, Paris Cedex 13, France
  3. 3Université Paris Diderot, Sorbonne Paris Cité, Paris, France
  4. 4AP-HP, Service D'immunologie Clinique, Hôpital Saint Louis, Paris, France
  5. 5Université de Clermont-Ferrand, Clermont-Ferrand, France
  6. 6CHU Clermont-Ferrand Service de Médecine Interne, Hôpital Gabriel Montpied, Clermont-Ferrand cedex1, France
  7. 7UPMC, Université Paris 6, Paris, France
  8. 8AP-HP, Service de Dermatologie Allergologie, Hôpital Tenon, Paris, France
  9. 9Université Paris-Decartes, Paris, France
  10. 10AP-HP, Service de Médecine Interne, Hôpital Cochin, Paris, France
  11. 11Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France
  12. 12AP-HP, Service de Rhumatologie, Hôpital Lariboisière, Paris, France
  13. 13CHU Amiens, Service de Médecine Interne, Hôpital Nord, Amiens, France
  14. 14AP-HP, Service de Médecine Interne, Hôpital Henri Mondor, Créteil, France
  15. 15Service de Médecine Interne, Hospices Civils de Lyon, Groupement Hospitalier Edouard Herriot, Lyon, France
  16. 16Service de Médecine Interne, Hôpital Foch, Suresnes, France
  17. 17Université de Toulouse III, Toulouse, France
  18. 18CHU Toulouse, Service de Néphrologie, Hôpital Rangueil, Toulouse, France
  19. 19CHU Toulouse, Service de Médecine Interne, Hôpital Purpan, Toulouse, France
  20. 20Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France
  21. 21AP-HP, Service de Médecine Interne, Hôpital Bichat Claude-Bernard, Paris, France
  22. 22Université Paris 13, Paris-cité, France
  23. 23AP-HP, Service de Médecine Interne, Hôpital Jean-Verdier, Bondy, France
  24. 24INSERM, UMR_S 959, F-75013, Paris, France
  25. 25CNRS, UMR 7211, F-75005, Paris, France
  26. 26AP-HP, Unité de Recherche Clinique, Hôpital Pitié-Salpêtrière, Paris Cedex 13, France
  27. 27AP-HP, Service de Pharmacologie, Hôpital Pitié-Salpêtrière, Paris Cedex 13, France
  28. 28AP-HP, Laboratoire d'immunochimie, Hôpital Pitié-Salpêtrière, Paris Cedex 13, France
  1. Correspondence to Professor Nathalie Costedoat-Chalumeau, AP-HP, Service de Médecine Interne, Faculté Paris 6, Hôpital Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, Paris 75013, France; nathalie.costedoat{at}gmail.com

Abstract

Introduction 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.

Patients and methods [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.

Results 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).

Conclusions Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up.

ClinicalTrials.gov NCT00413361

  • Systemic Lupus Erythematosus
  • Pharmacokinetics
  • Treatment

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