title: Randomized, double-blind, placebo-controlled study of safety and efficacy of miltefosine in antihistamine-resistant chronic spontaneous urticaria.
abstract: BACKGROUND
  Chronic spontaneous urticaria (CSU), a mast cell-driven condition, is debilitating, common, and hard to treat. Miltefosine, a lipid raft modulator, can inhibit mast cell responses in vivo.
  
  
  OBJECTIVE
  To study the safety and efficacy of systemic miltefosine treatment in CSU patients resistant to standard-dosed antihistamines.
  
  
  METHODS
  In this investigator-initiated multicentre, randomized, double-blind, placebo-controlled study, CSU patients were treated for 4 weeks with daily doses of up to 150-mg miltefosine (n = 47) or placebo (n = 26). Disease activity was assessed using the urticaria activity score. Safety and tolerability of miltefosine were also assessed.
  
  
  RESULTS
  After 4 weeks of treatment, Urticaria Activity Score (UAS7) levels were substantially more reduced in miltefosine-treated patients (-6.3 vs. -3.5 in placebo-treated patients; P = 0.05). Also, the number of weals, but not the intensity of pruritus, was significantly reduced in miltefosine-treated patients vs. placebo-treated patients (P = 0.02). In general, adverse events were frequent in both groups (miltefosine: 88%, placebo: 65% of patients) but mostly mild to moderate in severity. We did not observe any serious adverse events.
  
  
  CONCLUSIONS
  The results of this study indicate that miltefosine is an effective and safe treatment option for CSU patients who do not respond to standard-dosed antihistamines.
authors.affiliation: Department of Dermatology and Allergy; Allergie-Centrum-Charité; Charité- Universitätsmedizin Berlin, Berlin, Germany Department Clinical Operations, X-pert Med GmbH, Gräfelfing, Germany Department of Dermatology and Allergy, University of Bonn, Bonn, Germany Department of Dermatology, Eberhard Karls University Tübingen, Tübingen, Germany Department of Dermatology and Allergy, UK-SH, Campus Kiel, Kiel, Germany Praxisklinik und Gemeinschaftspraxis, Dülmen, Germany Department of Dermatology and Allergy, Universitätsklinikum Köln, Cologne, Germany Department of Dermatology and Allergy, Universitäts-Hautklinik Freiburg, Freiburg, Germany Department of Dermatology, University Hospital Erlangen, Erlangen, Germany Licca Clinical Research Institute, Augsburg, Germany Department of Dermatology, Universitätsklinikum Heidelberg, Heidelberg, Germany Jado Technologies GmbH, Dresden, Germany Department of Occupational and Social Medicine, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Germany Department of Dermatology, Venerology and Allergy, Universitätklinikum Leipzig, Leipzig, Germany Department of Dermatology and Allergy, Universitätsmedizin Mainz, Mainz, Germany Department of Dermatology and Allergy, Medizinische Hochschule Hannover, Hannover, Germany X-pert Med GmbH, Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Magerl
authors.forename: M
authors.initials: M
authors.lastname: Rother
authors.forename: T
authors.initials: T
authors.lastname: Bieber
authors.forename: T
authors.initials: T
authors.lastname: Biedermann
authors.forename: J
authors.initials: J
authors.lastname: Brasch
authors.forename: R
authors.initials: R
authors.lastname: Dominicus
authors.forename: N
authors.initials: N
authors.lastname: Hunzelmann
authors.forename: T
authors.initials: T
authors.lastname: Jakob
authors.forename: V
authors.initials: V
authors.lastname: Mahler
authors.forename: G
authors.initials: G
authors.lastname: Popp
authors.forename: K
authors.initials: K
authors.lastname: Schäkel
authors.forename: R
authors.initials: R
authors.lastname: Schlingensiepen
authors.forename: J
authors.initials: J
authors.lastname: Schmitt
authors.forename: F
authors.initials: F
authors.lastname: Siebenhaar
authors.forename: J C
authors.initials: JC
authors.lastname: Simon
authors.forename: P
authors.initials: P
authors.lastname: Staubach
authors.forename: B
authors.initials: B
authors.lastname: Wedi
authors.forename: C
authors.initials: C
authors.lastname: Weidner
authors.forename: M
authors.initials: M
authors.lastname: Maurer
mesh_terms: D002908:Chronic Disease; D004311:Double-Blind Method; D006633:Histamine Antagonists / Q000627:therapeutic use*; D006801:Humans; D010767:Phosphorylcholine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010919:Placebos; D014581:Urticaria / Q000188:drug therapy*
chemical_list: D006633:Histamine Antagonists; D010919:Placebos; D010767:Phosphorylcholine; C039128:miltefosine