Systemic Immunosuppressants

“Conventional systemic” treatments are oral drugs that broadly damp down the immune system. The main ones are ciclosporin (CyA) and methotrexate (MTX); azathioprine and mycophenolate are used less often. Specialists use them for severe Atopic Dermatitis that has not responded to potent topical treatment (Topical Corticosteroids, Topical Calcineurin Inhibitors, Wet Wrap Therapy). Ciclosporin is a calcineurin inhibitor, the same mechanism as topical Tacrolimus but taken by mouth. It blocks T-cell activation and works quickly. Methotrexate is a folic-acid antagonist that acts more slowly and may have some disease-modifying effect (Flohr, BJD 2023). Neither is licensed for AD in children. Ciclosporin has an adult AD licence in the UK/EU, and methotrexate is used off-label (Flohr 2023).

Systemic Immunosuppressants [treats] Atopic Dermatitis Systemic Immunosuppressants [relates] Topical Calcineurin Inhibitors Systemic Immunosuppressants [opposes] Th2 Immune Response

The TREAT trial. The TREAT Trial (Flohr et al., BJD 2023) was the first robust RCT of these drugs in children. It randomised 103 children and young people aged 2–16 at 13 UK and Irish centres, all with severe AD that potent topical treatment had not controlled. They got ciclosporin 4 mg/kg daily or methotrexate 0.4 mg/kg weekly (with folic acid) for 36 weeks, then 24 weeks of follow-up. Ciclosporin worked faster: o-SCORAD was 5.69 points better at 12 weeks, and o-SCORAD 50 was more likely (OR 2.60). By 60 weeks methotrexate was ahead (OR 0.33 for o-SCORAD 50 favouring MTX), and children had fewer flares after stopping it. Quality of life improved on both, and Filaggrin status did not change outcomes. A NIHR economic evaluation concluded that methotrexate is an effective, low-cost first-line systemic where newer drugs are restricted (PubMed 41337631, search snippet) (unverified).

TREAT Trial [supports] Systemic Immunosuppressants Systemic Immunosuppressants [relates] SCORAD Systemic Immunosuppressants [relates] Filaggrin

Safety and monitoring. In TREAT, adverse events were common and similar in both arms (94% vs 92%), mostly mild. Serious adverse events affected 10% on ciclosporin and 14% on methotrexate. One child in each arm was admitted with Eczema Herpeticum (moderate on ciclosporin, severe on methotrexate), and one child on methotrexate was admitted with shingles. On ciclosporin, the most frequent problems were flares (43%), headache (27%), an eGFR fall of more than 20% (27.5%), stomach pain and vomiting. Long-term ciclosporin risks hypertension and kidney damage, and use in children is recommended for a maximum of about one year. Methotrexate causes nausea (two children stopped because of it), fatigue and liver enzyme rises, and rarely bone marrow suppression. It needs regular blood tests. The authors said blood monitoring in children “can be rationalized” because few signals appeared.

Infection risk on systemic immunosuppressants

These drugs lower immune defences. Sudden painful punched-out sores, fever or a rapidly worsening rash on ciclosporin or methotrexate need urgent review for Eczema Herpeticum or other serious infection.

Systemic Immunosuppressants [relates] Eczema Herpeticum Systemic Immunosuppressants [relates] Infected Eczema

Place for toddlers today. TREAT included children from age 2 only, and its results are not broken down for under-5s. For 1–4-year-olds with severe AD, Dupilumab is now licensed from 6 months (US/EU). It is the only licensed systemic option at that age (Paller 2026). Oral baricitinib, one of the JAK Inhibitors, is EU-licensed from age 2. Conventional systemics remain important where biologics are unaffordable or not funded, which is the explicit argument in TREAT for lower-resource settings.

Dupilumab [relates] Systemic Immunosuppressants JAK Inhibitors [relates] Systemic Immunosuppressants

What parents report (evidence: anecdotal). Parent reports of systemic treatment in young children mostly involve oral steroid courses. One parent’s 5-year-old “hasn’t responded well to anything other than courses of prednisone, which turns him into a jack rabbit on crack” before switching to dupilumab (r/eczema). An adult recalls “nothing helped me until i got on prednisone pills” as a child. See Parent Experiences.

Systemic Immunosuppressants [relates] Parent Experiences

Connections

• TREAT Trial — CyA vs MTX RCT, ages 2–16, source: Flohr BJD 2023
• Atopic Dermatitis — treats severe disease, source: Flohr BJD 2023
• Dupilumab — licensed systemic alternative from 6 months, source: FDA/EMA labels
• JAK Inhibitors — newer systemic class; baricitinib EU ≥2 y, source: EMA Olumiant
• Tacrolimus — shares calcineurin-inhibitor mechanism with ciclosporin, source: Flohr BJD 2023
• Eczema Herpeticum — serious adverse event in both TREAT arms, source: Flohr BJD 2023
• Filaggrin — FLG status did not affect response, source: Flohr BJD 2023
• SCORAD — o-SCORAD primary outcome, source: Flohr BJD 2023
• Parent Experiences — parent reports (anecdotal), source: round-10 forum threads
• AAD Pediatric Guideline 2026 — methotrexate conditional ≥2 y; ciclosporin/azathioprine/MMF conditional; systemic steroids against, source: JAAD 2026