Methotrexate in the Treatment of Chronic Idiopathic Urticaria (MUCIS)

Randomized Clinical Trial Evaluating the Efficacy of Methotrexate in Addition to Anti-H1 Versus Placebo and Anti-H1 in the Treatment of Severe Chronic Idiopathic Urticaria

Chronic urticaria is defined by urticarial lesions persisting at 6 weeks. The cause is not found in about 75% of cases (chronic idiopathic urticaria). The gold standard treatment consists of anti-H1 molecules. In severe cases, refractory to anti-H1, few therapeutic alternatives exist. Methotrexate, which is not expensive and often prescribed by dermatologists, has been efficiently tried in an open study on severe chronic idiopathic urticaria, and also in few case reports.

Study Overview

• Status: Completed
• Conditions: Chronic Urticaria
• Intervention / Treatment: Drug: Methotrexate (Novatrex ®) + anti-H1; Drug: Placebo + anti-H1

Detailed Description

Chronic urticaria, defined by its persistence beyond 6 weeks, is a common condition (0.1% to 3% of the general population), occurring at any age. The etiology is not found in nearly 75% of cases (chronic idiopathic urticaria). Chronic idiopathic urticaria may resolve over several months or years. The quality of life of patients is usually strongly spoiled. The gold standard treatment consist of anti-H1 molecules. In severe cases, which are refractory to anti-H1, few therapeutic alternatives exist. Two studies have shown a benefit when adding to anti-H1, montelukast, anti-leukotriene, or cyclosporine. Methotrexate, which is another immunosuppressive drug, cheap and commonly prescribed by dermatologists, has been efficient in severe chronic urticaria, in an open study and in few case reports.

Methotrexate, an anti-metabolite drug which inhibits dihydrofolate reductase, is indicated in hematologic malignancies and in autoimmune diseases. It may be given by oral or parenteral administration, once a week, and requires regular monitoring of renal and hepatic function, and blood count.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Brest, France, 29000
    • CHRU BREST Morvan
  • Créteil, France, 94000
    • CHU Mondor
  • Le Mans, France, 72000
    • CH Le Mans
  • Lille, France, 59000
    • CHRU LILLE Huriez
  • Nancy, France, 54000
    • Chru Nancy Brabois
  • Nantes, France, 44000
    • CHRU Nantes
  • Paris, France, 75020
    • Hôpital Tenon
  • Poitiers, France, 86000
    • CHRU POITIERS La Miléterie
  • Reims, France, 51000
    • CHRU Reims
  • Rennes, France, 35000
    • CHRU RENNES Pontchaillou
  • Tours, France, 37044
    • CHRU Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients who met the diagnostic criteria for chronic idiopathic urticaria, previously treated by

• 3 different molecules of anti-H1 or
• a combination of 2 different molecules of anti-H1 or
• 1 molecule of anti-H1 with at least a double dose for a total treatment duration of ≥ 3 months before inclusion
• With persistency of at least 7 days with urticarial lesions in the previous month

Exclusion Criteria:

• Differential diagnosis of chronic idiopathic urticaria (urticarial vasculitis)
• Treatment with montelukast or immunosuppressive drugs during the previous month

• Contraindications to methotrexate

  • Allergy to methotrexate
  • Treatment which are contraindicated with methotrexate
  • Pregnancy, possibility of getting pregnant (no effective contraception), breastfeeding
  • Anomalies in liver function (transaminases or liver failure at a rate 1.5 X normal)
  • Severe renal impairment (creatinine clearance calculated by the cockcroft formula <50 ml / min)
  • Chronic respiratory failure
  • Active infectious chronic diseases (viral hepatitis, HIV)
  • History of neoplasia
  • Mental deficiency
  • Involvement in another drug clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group I; The group I will receive the intervention : Methotrexate + anti-H1	Drug: Methotrexate (Novatrex ®) + anti-H1; Methotrexate (Novatrex ®) tablets 2.5 mg methotrexate 0.2 mg/kg/week as a single dose, orally for 8 weeks. After 8 weeks, if the treatment is still not efficient, the dose will be increased to 0.25 mg/kg/week and continued until W18. For anti-H1 treatment, the same molecules with the same dosage than before the recruitment will be continued, and methotrexate will be added in this group.; Other Names: Methotrexate; Anti-H1
Placebo Comparator: Group II; The intervention in group II will include : placebo + anti-H1	Drug: Placebo + anti-H1; Placebo: 0.2 mg / kg / week as a single dose, orally for 8 weeks. After eight weeks, if the patient is still very embarrassed, the dose is increased to 0.25 mg / kg / week in a weekly dose. For anti-H1 treatment, the same molecules with the same dosage than before the recruitment will be continued, and the placebo of methotrexate will be added in this group.; Other Names: Placebo of methetrexate + anti-H1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with complete remission of urticaria at 18 weeks	Number of patients with complete remission of urticaria at 18 weeks, defined as no urticarial lesion 30 days before W18	at 18 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance : clinical and biological safety	Number of patients with clinical adverse effects Number of patients with biological adverse effects	18 weeks
Efficacy of the treatment in improving symptoms : pruritus	Number of patients with : - pruritus At 18 weeks and 26 weeks	18 weeks and 26 weeks
Persistency of the complete remission at 26 weeks	Number of patients with persistency of the complete remission, defined as no urticarial lesion from the withdrawal of treatment until W26	26 weeks
Efficacy of the treatment in improving symptoms : outbreaks by week	- number of outbreaks by week/patient At 18 weeks and 26 weeks	18 weeks and 26 weeks
Efficacy of the treatment in improving symptoms : duration of lesions	- mean +/- standard deviation duration of lesions At 18 weeks and 26 weeks	18 weeks and 26 weeks
Efficacy of the treatment in improving quality of life	Mean DLQI (quality of life) score : At 18 weeks and 26 weeks	18 weeks and 26 weeks
Efficacy of the treatment in improving quality of sleep	Mean score of quality of sleep (from 0 to 100) At 18 weeks and 26 weeks	18 weeks and 26 weeks
Efficacy of the treatment in improving facial/cervical urticarial lesions	Number of patients with, either : facial/cervical urticarial lesions; urticarial lesions on the body only; facial/cervical + body lesions Indeed, facial or cervical urticarial lesions are considered more disturbing. At W18 and W26	18 weeks and 26 weeks

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Investigators: Principal Investigator: Annabel MARUANI, MD, PhD, University Hospital of TOURS, France

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2011
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: January 15, 2013
• First Submitted That Met QC Criteria: October 8, 2013
• First Posted (Estimate): October 10, 2013

Study Record Updates

• Last Update Posted (Actual): September 20, 2017
• Last Update Submitted That Met QC Criteria: September 19, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Chronic Urticaria; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: PHRN09-AM/MUCIS