Systemic Therapies for Severe/Refractory Atopic Dermatitis

Primary Recommendations

The American Academy of Dermatology recommends dupilumab as the first-line systemic therapy for severe/refractory atopic dermatitis due to its excellent safety profile and proven efficacy over more than 5 years of clinical use 1, 2, 3

High-dose upadacitinib (30 mg daily) and high-dose abrocitinib (200 mg daily) demonstrate the highest efficacy at reducing EASI scores up to 16 weeks among all currently available treatments and were superior to dupilumab in head-to-head clinical trials 4, 5
Dupilumab (300 mg every 2 weeks) achieves EASI 75 in 63-64% of patients at 16 weeks when combined with topical corticosteroids 2, 3

The American Academy of Dermatology states that dupilumab has an excellent safety track record with few major emergent safety concerns after more than 5 years in clinical practice 1, 2, 3
Conjunctivitis is the most common adverse event (6-15% in trials, up to 26.1% in real-world data), but only 4.2% discontinue due to ocular complications 2, 3
FDA applied class warnings for JAK inhibitors including increased risk of serious heart-related events, cancer, blood clots, and death based on data from tofacitinib in rheumatoid arthritis patients aged ≥50 years with cardiovascular risk factors 4

The American Academy of Dermatology recommends initiating dupilumab for patients with moderate-to-severe atopic dermatitis affecting multiple body areas with inadequate response to optimized topical therapies and significant quality of life impairment 2, 3
Dosing: 600 mg subcutaneous loading dose, then 300 mg every 2 weeks 5, 2
No laboratory monitoring required 1

Patients requiring faster onset of action should be considered for JAK inhibitors over dupilumab 2
Patients with pre-existing severe ocular surface disease who cannot tolerate conjunctivitis risk should be considered for JAK inhibitors over dupilumab 2, 3
Methotrexate should be reserved for severe/refractory cases only when FDA-approved biologics and JAK inhibitors are not accessible 6

Systemic corticosteroids should not be used for atopic dermatitis due to substantial risk of serious adverse events and rebound flares upon discontinuation (conditional recommendation against) 7, 2
JAK inhibitors should not be used as first-line therapy unless biologics are contraindicated or unavailable, as they are FDA-approved only after failure of other systemic therapies 4, 5