title: Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study).
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: UPMC, Université Paris 6, , Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Costedoat-Chalumeau
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.forename: Olivier
authors.initials: O
authors.lastname: Aumaître
authors.forename: Camille
authors.initials: C
authors.lastname: Francès
authors.forename: Véronique
authors.initials: V
authors.lastname: Le Guern
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lioté
authors.forename: Amar
authors.initials: A
authors.lastname: Smail
authors.forename: Nicolas
authors.initials: N
authors.lastname: Limal
authors.forename: Laurent
authors.initials: L
authors.lastname: Perard
authors.forename: Hélène
authors.initials: H
authors.lastname: Desmurs-Clavel
authors.forename: Du Le Thi Huong
authors.initials: du LT
authors.lastname: Boutin
authors.forename: Bouchra
authors.initials: B
authors.lastname: Asli
authors.forename: Jean-Emmanuel
authors.initials: JE
authors.lastname: Kahn
authors.forename: Jacques
authors.initials: J
authors.lastname: Pourrat
authors.forename: Laurent
authors.initials: L
authors.lastname: Sailler
authors.forename: Félix
authors.initials: F
authors.lastname: Ackermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Papo
authors.forename: Karim
authors.initials: K
authors.lastname: Sacré
authors.forename: Olivier
authors.initials: O
authors.lastname: Fain
authors.forename: Jerome
authors.initials: J
authors.lastname: Stirnemann
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
authors.forename: Moez
authors.initials: M
authors.lastname: Jallouli
authors.forename: Gaelle
authors.initials: G
authors.lastname: Leroux
authors.forename: Judith
authors.initials: J
authors.lastname: Cohen-Bittan
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Tanguy
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
authors.forename: Philippe
authors.initials: P
authors.lastname: Lechat
authors.forename: Lucile
authors.initials: L
authors.lastname: Musset
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Piette
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005602:France; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage* / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine
keywords: Pharmacokinetics; Systemic Lupus Erythematosus; Treatment