Methotrexate Versus Cyclosporine in Adults with Moderate-to-Severe Atopic Dermatitis: A Phase III Randomized Noninferiority Trial

J Allergy Clin Immunol Pract. 2018 Mar-Apr;6(2):562-569.e3. doi: 10.1016/j.jaip.2017.07.007. Epub 2017 Sep 28.

Abstract

Background: Methotrexate is currently used to treat atopic dermatitis but has never been assessed versus cyclosporine in adults.

Objective: This study evaluated the efficacy and safety of methotrexate versus cyclosporine in patients with moderate-to-severe atopic dermatitis.

Methods: Patients were randomized to receive either oral methotrexate (15 mg/wk) or cyclosporine (2.5 mg/kg/d) for 8 weeks. The primary end point was a patient achieving 50% improvement in the SCORing Atopic Dermatitis index (SCORAD 50) at week 8. When the primary end point was not achieved, methotrexate was increased to 25 mg and cyclosporine to 5 mg during the next 16 weeks. The secondary end points were a patient achieving a 50% reduction in the Eczema Area Severity Intensity index (EASI 50) and SCORAD 50 at each visit (ClinicalTrials.gov no. NCT00809172).

Results: A total of 97 patients received methotrexate 15 mg (n = 50) or cyclosporine 2.5 mg (n = 47). Regarding the primary end point at week 8, methotrexate was inferior to cyclosporine because the proportion of patients with SCORAD 50 was 8% (4 of 50) in the methotrexate arm versus 42% (18 of 43) in the cyclosporine arm. The difference in percentages for the 2 treatment groups (2-sided 90% CI) was -34% (-48% to -20%). At week 8, methotrexate and cyclosporine dosages were increased in 56% and 49% of the patients, respectively. Regarding EASI 50, the noninferiority end point was reached at week 20 in 92% (22 of 24) of patients in the methotrexate arm and 87% (26 of 30) of patients in the cyclosporine arm. The treatment-related adverse events were more frequent with cyclosporine (P < .0001).

Conclusions: Methotrexate 15 mg/wk was inferior to cyclosporine 2.5 mg/kg/d at week 8. Increasing the doses of methotrexate to 25 mg/wk induced a significant improvement versus cyclosporine at week 20.

Keywords: Atopic dermatitis; Cyclosporine; Methotrexate; Trial.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cyclosporine / therapeutic use*
  • Dermatitis, Atopic / drug therapy*
  • Dermatologic Agents / therapeutic use*
  • Female
  • Humans
  • Male
  • Methotrexate / therapeutic use*
  • Severity of Illness Index
  • Single-Blind Method
  • Treatment Outcome
  • Young Adult

Substances

  • Dermatologic Agents
  • Cyclosporine
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT00809172