title: The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE): An open-label prospective pilot study.
abstract: BACKGROUND
  Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ).
  
  
  OBJECTIVE
  We sought to evaluate the efficacy of increased daily doses of HCQ on cutaneous response in refractory CLE.
  
  
  METHODS
  We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL.
  
  
  RESULTS
  We included 34 patients (26 women; median age 45 [range 28-72] years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 [range 2-30] vs 1.5 [range 0-30]), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 [range 3.06-77.4] months) was achieved in 15 of the 26 responders.
  
  
  CONCLUSIONS
  The main limitations of the study are its open-label design and the limited number of patients included.
  
  
  CONCLUSIONS
  Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE.
authors: Assistance Publique Hôpitaux de Paris (AP-HP), Service de Dermatologie et d'Allergologie, Hôpital Tenon, F-75020, Paris, France.
authors: François
authors: F
authors: Chasset
authors: Inserm Unité mixte de Recherche-S (UMR-S) 1136, Groupe Recherche (GR-08), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Hôpital Pitié-Salpêtrière, F-75013, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, F-75013, Paris, France.
authors: Laurent
authors: L
authors: Arnaud
authors: Université René Descartes Paris V, F-75005, Paris, France; AP-HP, Centre de Référence Maladies Auto-immunes et Systémiques Rares, Service de Médecine Interne Pôle Médecine, Hôpital Cochin, F-75014, Paris, France.
authors: Nathalie
authors: N
authors: Costedoat-Chalumeau
authors: AP-HP, Service de Pharmacologie, Hôpital Pitié-Salpêtrière, F-75013, Paris, France.
authors: Noel
authors: N
authors: Zahr
authors: Université Montpellier, Service de Dermatologie, Centre Hospitalo-Universitaire de Montpellier, Institut National de la Santé et de la Recherche Médicale (INSERM) 1058, Montpellier, France.
authors: Didier
authors: D
authors: Bessis
authors: Assistance Publique Hôpitaux de Paris (AP-HP), Service de Dermatologie et d'Allergologie, Hôpital Tenon, F-75020, Paris, France. Electronic address: camille.frances@tnn.aphp.fr.
authors: Camille
authors: C
authors: Francès
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*; D008178:Lupus Erythematosus, Cutaneous / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D006886:Hydroxychloroquine
keywords: antimalarials; cutaneous lupus erythematosus; hydroxychloroquine; hydroxychloroquine blood concentration; increasing dose; retinal toxicity