TREAT Trial

Design and population. The TREAT trial (Flohr et al., Br J Dermatol 2023) was a multicentre, assessor-blinded, parallel-group superiority RCT at 12 UK paediatric dermatology departments and one in Ireland. Between 2016 and 2019 it randomised 103 children and young people aged 2–16 (mean age about 10) with severe, recalcitrant Atopic Dermatitis that potent topical treatment had not controlled: 52 to ciclosporin and 51 to methotrexate. Mean baseline EASI was 27–29. It was the first adequately powered RCT of the two most-used conventional Systemic Immunosuppressants in children. TREAT Trial [part-of] Systemic Immunosuppressants

Intervention and primary outcome. Children took oral ciclosporin 4 mg/kg daily or methotrexate 0.4 mg/kg weekly (with folic acid) for 36 weeks, then were followed for 24 weeks off treatment. The co-primary outcomes were change in objective SCORAD (o-SCORAD) from baseline to 12 weeks, and time to first significant flare after stopping. SCORAD [defines] TREAT Trial

Result. Ciclosporin worked faster: o-SCORAD improved 5.69 points more by week 12 (97.5% CI −10.81 to −0.57), o-SCORAD 50 was more likely (OR 2.60), and EASI-75 at week 12 was 44% vs 20%. By week 36 the two were similar (EASI-75 42% vs 46%). After stopping, methotrexate was better: at week 60 it led on o-SCORAD 50 (OR 0.33 in favour of MTX), and children reported more flares after ciclosporin. Quality of life improved on both and Filaggrin status did not change outcomes. Adverse events were common and similar; serious adverse events affected 10% on ciclosporin and 14% on methotrexate, and one child on ciclosporin had Eczema Herpeticum. TREAT Trial [supports] Systemic Immunosuppressants TREAT Trial [relates] Eczema Herpeticum

Limitations. Children, families and local doctors knew which drug was given; only the severity assessor was blinded. There was no placebo arm, so it compares two active drugs. Methotrexate seemed not to have reached its full effect by 36 weeks, and itch was not measured. Neither drug is licensed for eczema in children, and the trial predates routine use of Dupilumab and JAK Inhibitors, so it does not compare against them. TREAT Trial [relates] Dupilumab

What it means for toddlers. TREAT enrolled children from age 2, but most were school-age and results are not reported separately for under-5s. For a 1–4-year-old with severe eczema, these drugs are specialist-only, off-label options with blood and blood-pressure monitoring. Dupilumab is now licensed from 6 months and is the only licensed systemic option at that age (see Systemic Immunosuppressants). Where it is not available, TREAT supports methotrexate as an effective, low-cost choice and ciclosporin when quick control is needed. Dupilumab [relates] TREAT Trial

Connections

• Systemic Immunosuppressants — supports; key paediatric RCT, source: Flohr BJD 2023
• SCORAD — o-SCORAD co-primary outcome, source: Flohr BJD 2023
• EASI — EASI-75 secondary outcome (44% vs 20% at week 12), source: Flohr BJD 2023
• Eczema Herpeticum — serious adverse event on ciclosporin, source: Flohr BJD 2023
• Filaggrin — FLG status did not change response, source: Flohr BJD 2023
• Dupilumab — licensed alternative for under-6s, source: Systemic Immunosuppressants note