A randomized controlled trial protocol assessing the effectiveness, safety and cost-effectiveness of methotrexate vs. ciclosporin in the treatment of severe atopic eczema in children: the TREatment of severe Atopic eczema Trial (TREAT)

Br J Dermatol. 2018 Dec;179(6):1297-1306. doi: 10.1111/bjd.16717. Epub 2018 Oct 28.

Abstract

Background: Oral systemic immunomodulatory medication is regularly used off-licence in children with severe atopic eczema. However, there is no firm evidence regarding the effectiveness, safety, cost-effectiveness and impact on quality of life from an adequately powered randomized controlled trial (RCT) using systemic medication in children.

Objectives: To assess whether there is a difference in the speed of onset, effectiveness, side-effect profile and reduction in flares post-treatment between ciclosporin (CyA) and methotrexate (MTX), and also the cost-effectiveness of the drugs. Treatment impact on quality of life will also be examined in addition to whether FLG genotype influences treatment response. In addition, the trial studies the immune-metabolic effects of CyA and MTX.

Methods: Multicentre, parallel group, assessor-blind, pragmatic RCT of 36 weeks' duration with a 24-week follow-up period. In total, 102 children aged 2-16 years with moderate-to-severe atopic eczema, unresponsive to topical treatment will be randomized (1 : 1) to receive MTX (0·4 mg kg-1 per week) or CyA (4 mg kg-1 per day).

Results: The trial has two primary outcomes: change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare following treatment cessation.

Conclusions: This trial addresses important therapeutic questions, highlighted in systematic reviews and treatment guidelines for atopic eczema. The trial design is pragmatic to reflect current clinical practice.

Publication types

  • Clinical Trial Protocol
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Child
  • Child, Preschool
  • Cost-Benefit Analysis*
  • Cyclosporine / administration & dosage*
  • Cyclosporine / adverse effects
  • Cyclosporine / economics
  • Dermatitis, Atopic / diagnosis
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / economics
  • Dermatitis, Atopic / genetics
  • Dermatologic Agents / administration & dosage*
  • Dermatologic Agents / adverse effects
  • Dermatologic Agents / economics
  • Female
  • Filaggrin Proteins
  • Humans
  • Intermediate Filament Proteins / genetics
  • Male
  • Methotrexate / administration & dosage*
  • Methotrexate / adverse effects
  • Methotrexate / economics
  • Multicenter Studies as Topic
  • Pragmatic Clinical Trials as Topic
  • Randomized Controlled Trials as Topic
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Dermatologic Agents
  • FLG protein, human
  • Filaggrin Proteins
  • Intermediate Filament Proteins
  • Cyclosporine
  • Methotrexate