title: A randomized placebo-controlled double-blind pilot study of methotrexate in the treatment of H1 antihistamine-resistant chronic spontaneous urticaria.
abstract: BACKGROUND
  Chronic urticaria not responsive to antihistamines is a difficult disease to manage. Methotrexate has been used in difficult chronic urticarias with some benefit.
  
  
  OBJECTIVE
  To evaluate the efficacy of methotrexate in the treatment of chronic spontaneous urticaria poorly responsive to H1 antihistaminics.
  
  
  METHODS
  In a randomized double-blind trial at the Department of Dermatology and Venereology of a tertiary care centre, 29 patients with chronic spontaneous urticaria not responding well to H1 antihistaminics were recruited. Patients were randomly allocated to receive either a weekly dose of oral methotrexate 15 mg or placebo (calcium carbonate) for a total duration of 12 weeks, after which treatment was stopped and patients were followed up for relapse of urticaria. Each group also received levocetrizine 5 mg once daily for symptom control. Primary outcome measured was a reduction by >2/3 rd of baseline urticaria scores after 12 week therapy. Secondary outcome was a reduction in antihistamine requirement after stopping therapy.
  
  
  RESULTS
  Fourteen patients were randomized to the methotrexate group and fifteen patients to the placebo group. Out of 17 patients who completed therapy, the primary outcome was achieved by 3.5 ± 1.9 (out of 10) patients in the methotrexate group and by 3.67 ± 1.03 (out of 7) patients in the placebo group (P > 0.05). Ten patients followed up, after stopping therapy, for a mean period of 3.5 ± 2.4 months; 3 remained in remission and 7 had relapsed. One patient had uncontrollable nausea and vomiting after taking methotrexate and was withdrawn from the study. The placebo group did not experience any side effects.
  
  
  CONCLUSIONS
  Methotrexate 15 mg weekly for 3 months did not provide any additional benefit over H1 antihistamines in this study but an adequately powered study with longer follow up is required to assess its utility.
authors.affiliation: Departments of Dermatology, Venereology and Leprology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Sharma
authors.forename: Saurabh
authors.initials: S
authors.lastname: Singh
authors.forename: M
authors.initials: M
authors.lastname: Ramam
authors.forename: Mahesh
authors.initials: M
authors.lastname: Kumawat
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D003879:Dermatologic Agents / Q000008:administration & dosage; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006634:Histamine H1 Antagonists / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D010865:Pilot Projects; D010919:Placebos; D016896:Treatment Outcome; D014581:Urticaria / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D003879:Dermatologic Agents; D006634:Histamine H1 Antagonists; D010919:Placebos; D008727:Methotrexate