title: Effects of hydroxychloroquine on symptomatic improvement in primary Sjögren syndrome: the JOQUER randomized clinical trial.
abstract: OBJECTIVE
  Primary Sjögren syndrome is a systemic autoimmune disease characterized by mouth and eye dryness, pain, and fatigue. Hydroxychloroquine is the most frequently prescribed immunosuppressant for the syndrome. However, evidence regarding its efficacy is limited.
  
  
  OBJECTIVE
  To evaluate the efficacy of hydroxychloroquine for the main symptoms of primary Sjögren syndrome: dryness, pain, and fatigue.
  
  
  METHODS
  From April 2008 to May 2011, 120 patients with primary Sjögren syndrome according to American-European Consensus Group Criteria from 15 university hospitals in France were randomized in a double-blind, parallel-group, placebo-controlled trial. Participants were assessed at baseline, week 12, week 24 (primary outcome), and week 48. The last follow-up date for the last patient was May 15, 2012.
  
  
  METHODS
  Patients were randomized (1:1) to receive hydroxychloroquine (400 mg/d) or placebo until week 24. All patients were prescribed hydroxychloroquine between weeks 24 and 48.
  
  
  METHODS
  The primary end point was the proportion of patients with a 30% or greater reduction between weeks 0 and 24 in scores on 2 of 3 numeric analog scales (from 0 [best] to 10 [worst]) evaluating dryness, pain, and fatigue.
  
  
  RESULTS
  At 24 weeks, the proportion of patients meeting the primary end point was 17.9% (10/56) in the hydroxychloroquine group and 17.2% (11/64) in the placebo group (odds ratio, 1.01; 95% CI, 0.37-2.78; P = .98). Between weeks 0 and 24, the mean (SD) numeric analog scale score for dryness changed from 6.38 (2.14) to 5.85 (2.57) in the placebo group and 6.53 (1.97) to 6.22 (1.87) in the hydroxychloroquine group. The mean (SD) numeric analog scale score for pain changed from 4.92 (2.94) to 5.08 (2.48) in the placebo group and 5.09 (3.06) to 4.59 (2.90) in the hydroxychloroquine group. The mean (SD) numeric analog scale for fatigue changed from 6.26 (2.27) to 5.72 (2.38) in the placebo group and 6.00 (2.52) to 5.94 (2.40) in the hydroxychloroquine group. All but 1 patient in the hydroxychloroquine group had detectable blood levels of the drug. Hydroxychloroquine had no efficacy in patients with anti-SSA autoantibodies, high IgG levels, or systemic involvement. During the first 24 weeks, there were 2 serious adverse events in the hydroxychloroquine group and 3 in the placebo group; in the last 24 weeks, there were 3 serious adverse events in the hydroxychloroquine group and 4 in the placebo group.
  
  
  CONCLUSIONS
  Among patients with primary Sjögren syndrome, the use of hydroxychloroquine compared with placebo did not improve symptoms during 24 weeks of treatment. Further studies are needed to evaluate longer-term outcomes.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00632866.
authors.affiliation: Department of Rheumatology, Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Centre de Référence National Pour les Maladies Auto-Immunes Systémiques Rares, Université de Strasbourg, Strasbourg, France.
authors.forename: Jacques-Eric
authors.initials: JE
authors.lastname: Gottenberg
authors.affiliation: Department of Epidemiology and Public Health, Hotel Dieu, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
authors.affiliation: Department of Internal Medicine, Cochin Hospital, AP-HP, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Puéchal
authors.affiliation: Department of Internal Medicine, Cochin Hospital, AP-HP, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Le Guern
authors.affiliation: Department of Rheumatology, Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Centre de Référence National Pour les Maladies Auto-Immunes Systémiques Rares, Université de Strasbourg, Strasbourg, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.affiliation: Department of Rheumatology, Amiens University Hospital, Amiens, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Goeb
authors.affiliation: Department of Internal Medicine, Avicenne Hospital, AP-HP, Bobigny, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Larroche
authors.affiliation: Department of Rheumatology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Dubost
authors.affiliation: Department of Rheumatology, Orléans Hospital, Orléans, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rist
authors.affiliation: Department of Rheumatology, Brest University Hospital, Brest, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Saraux
authors.affiliation: Department of Rheumatology, Brest University Hospital, Brest, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Devauchelle-Pensec
authors.affiliation: Department of Rheumatology, Montpellier University Hospital, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Morel
authors.affiliation: Department of Rheumatology, Hôpital Bichat, AP-HP, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Hayem
authors.affiliation: Department of Internal Medicine, Lille University Hospital, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Hatron
authors.affiliation: Department of Rheumatology, Rennes University Hospital, Rennes, France.
authors.forename: Aleth
authors.initials: A
authors.lastname: Perdriger
authors.affiliation: Department of Internal Medicine, Lariboisère Hospital, AP-HP, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Sene
authors.affiliation: Department of Rheumatology, Le Havre Hospital, Le Havre, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Zarnitsky
authors.affiliation: Department of Rheumatology, Hôpitaux Universitaires Paris-Sud, AP-HP, INSERM U 1012, Université Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Djilali
authors.initials: D
authors.lastname: Batouche
authors.affiliation: Department of Pharmacy, Hôpitaux Universitaires Paris-Sud, AP-HP, Le Kremlin Bicêtre, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Furlan
authors.affiliation: Department of Centre de Ressources Biologiques, Bichat Hospital, AP-HP, Paris, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Benessiano
authors.affiliation: Department of Epidemiology and Public Health, Hotel Dieu, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Perrodeau
authors.affiliation: Department of Rheumatology, Hôpitaux Universitaires Paris-Sud, AP-HP, INSERM U 1012, Université Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Raphaele
authors.initials: R
authors.lastname: Seror
authors.affiliation: Department of Rheumatology, Hôpitaux Universitaires Paris-Sud, AP-HP, INSERM U 1012, Université Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005221:Fatigue / Q000188:drug therapy / Q000209:etiology; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D012859:Sjogren's Syndrome / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D006886:Hydroxychloroquine