title: Systematic review of treatments for chronic spontaneous urticaria with inadequate response to licensed first-line treatments.
abstract: BACKGROUND
  Patients with chronic spontaneous urticaria (CSU) are sometimes unresponsive to nonsedating, second-generation, H1 antihistamines; this study summarizes published clinical evidence for patients who remain symptomatic despite treatment.
  
  
  OBJECTIVE
  To evaluate, via a systematic literature review, clinical evidence of management strategies for patients with CSU who remain symptomatic despite approved use of nonsedating H1 antihistamines.
  
  
  METHODS
  Using a prespecified protocol, we searched MEDLINE, Embase, the Cochrane Library (1 January 1960-20 December 2011), and published conference abstracts (2010-2012). Rigorous criteria identified trials in patients with CSU who had a history of inadequate response to previous treatment or had used combination treatments. Trials evaluating treatment-naïve patients or first-line therapies were excluded.
  
  
  RESULTS
  Qualitative data synthesized from 26 randomized, controlled trials, four prospective studies, and one retrospective study showed cyclosporine, desloratadine plus dapsone or dipyridamole, montelukast, and omalizumab reduced urticaria activity scores, weals, and pruritus, versus placebo. Optimal treatment doses and durations were unclear due to varying trial durations, outcome measurement scales, and assessment timings. No safety concerns were reported.
  
  
  CONCLUSIONS
  This review confirms that available evidence to guide treatment choice for patients with CSU with inadequate response to H1 antihistamines varies in quality. Further research is warranted due to low-quality trials with methodological and reporting limitations.
authors.affiliation: RTI Health Solutions, Manchester, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mitchell
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Maria-Magdalena
authors.initials: MM
authors.lastname: Balp
authors.affiliation: RTI Health Solutions, Manchester, UK.
authors.forename: Miny
authors.initials: M
authors.lastname: Samuel
authors.affiliation: RTI Health Solutions, Manchester, UK.
authors.forename: Doreen
authors.initials: D
authors.lastname: McBride
authors.affiliation: Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité, Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
mesh_terms: D018680:Cholinergic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D005260:Female; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D017211:Treatment Failure; D014581:Urticaria / Q000175:diagnosis* / Q000188:drug therapy*
chemical_list: D018680:Cholinergic Antagonists; D039563:Histamine H1 Antagonists, Non-Sedating