Current Perspectives on the Systemic Management of Atopic Dermatitis

Figures & data

Table 1 Mechanism, Dosing, and Monitoring of Systemic Therapies^a

Systemic Agent	Mechanism	Starting Dose	Dose Adjustment	Baseline Assessment	Follow-Up Monitoring	Historic FDA Pregnancy Risk Category^b	Newer Pregnancy Rating^b
Cyclosporine A (CsA)^Citation32	Inhibits production of IL-2 resulting in decreased T-cell proliferation	1. Initial high dose regimen: 5 mg/kg daily in two divided doses for 2–3 months	1. Initial high dose regimen: Reduce in decrements of 1 mg/kg daily every other week until the minimum effective dose is reached	2 blood pressures at least a day apart; 2 serum creatinine levels at least a day apart; BUN; CBC; LFTs; fasting lipids; magnesium; potassium; uric acid	Blood pressure at each visit every 2 weeks for 1–2 months, then every 4–6 weeks; labs every 2 weeks for the first 1–2 months, then monthly; labs should include serum creatinine, BUN, urinalysis, CBC, LFTs, lipids, magnesium, potassium, uric acid	Category C	Probably compatible
		2. Initial low dose regimen: 2.5–3 mg/kg daily for 1 month	2. Initial low dose regimen: Increase in increments of 0.5–1 mg/kg daily every 2 weeks, not to exceed the maximum dose of 5 mg/kg daily
Azathioprine (AZA)^Citation41	Inhibits purine metabolism and cell division via incorporation into DNA and RNA	1. Low TPMT (<6.3 U/mL): Do not use AZA	Consider rechecking TPMT level if a sudden change in efficacy occurs	Pregnancy test; CBC with platelet count; CMP; urinalysis; tuberculosis testing; TPMT function assay	Labs every 2 weeks for the first 2 months, then every 2–3 months; labs should include CBC with differential and LFTs	Category D	Low risk (second trimester); Moderate-high risk (third trimester)
		2. Intermediate TPMT (6.3 to 15 U/mL): Up to 1 mg/kg daily
		3. High TPMT (>15.1 to 26.4 U/mL): Up to 2–3 mg/kg daily
Methotrexate (MTX)^Citation49	Inhibits dihydrofolate reductase (DHFR) resulting in decreased DNA and RNA synthesis and proliferation of lymphocytes	Doses should be administered weekly in a single weekly dose or three divided doses over a 24-hour period. Initiate with a dose of 0.3–0.5 mg/kg.	Increase in increments of 2.5–5 mg every week. When maximal benefit is achieved (total weekly dose rarely exceeds 30 mg) taper by 2.5 mg every week until the minimum effective dose is reached.	CBC with platelet count; LFTs; serologic tests for hepatitis B and C; BUN; serum creatinine; HIV testing in patients at risk for AIDS; tuberculosis testing in at risk patients	CBC with platelet count and LFTs after the first 2–4 weeks, 4 weeks after dose escalations, then every 3–4 months; BUN and serum creatinine once or twice yearly	Category X	Contraindicated
Mycophenolate mofetil (MMF)^Citation57	Inhibits inosine monophosphate dehydrogenase (IMPDH) resulting in decreased purine synthesis and proliferation of lymphocytes	Initiate with a dose of 20 mg/kg daily in two divided doses	If needed, increase to 40–50 mg/kg daily in two divided doses	Pregnancy test; CBC with differential and platelet count; CMP; LFTs; serologic tests for hepatitis B and C; tuberculosis testing	Consider monthly pregnancy test; labs every 4 weeks following dose escalation, then every 2–3 months; labs should include CBC with differential and platelet count, CMP, LFTs	Category D	Moderate-high risk
Dupilumab^Citation26,Citation64	Binds the IL-4 receptor α-subunit, which blocks downstream signaling of IL-4 and IL-13	Adults: Initiate with a dose of 600 mg (two 300 mg injections in different injection sites)	Adults: 300 mg every other week	None	None	Unrated	No Data
		Pediatric Patients: 1. (15 to <30kg): Initiate with a dose of 600 mg (two 300 mg injections)	Pediatric Patients: 1. (15 to <30kg): 300 mg every 4 weeks
		2. (30 to 60kg): Initiate with a dose of 400 mg (two 200 mg injections)	2. (30 to <60kg): 200 mg every other week
		3. (60kg or more): Initiate with a dose of 600 mg (two 300 mg injections)	3. (60kg or more): 300 mg every other week

Notes: Symbols: α, alpha; ≤, less than; ≥, greater than. ^aFor CsA, AZA, MTX and MMF there are no formal dosing or monitoring guidelines for atopic dermatitis. Recommendations vary and are based on other inflammatory conditions. Those presented here are drawn from Comprehensive Dermatologic Drug Therapy (Fourth Edition), 2021, as well as the authors’ experience. ^bOn June 30, 2015, the FDA made the Pregnancy and Lactation Labeling Rule (PLLR) effective for prescription drug labeling. The rule required the removal of pregnancy categories A, B, C, D and X from human prescription drug and biologic product labeling. The new labeling includes descriptive information regarding risks.

Abbreviations: BUN, blood urea nitrogen; CBC, complete blood count; LFTs, liver function tests; CMP, complete metabolic panel; HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome.

Sekhon S, Bhutani T, Koo JYM. 17 - Cyclosporine. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy (Fourth Edition). Elsevier; 2021:187–198.e3.

 Google Scholar

Grove D, Rahnama-Moghadam S. 15 - Azathioprine. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy (Fourth Edition). Elsevier; 2021:169–177.e3.

 Google Scholar

Callen JP, Kulp-Shorten CL. 14 - Methotrexate. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy (Fourth Edition). Elsevier; 2021:156–168.e5.

 Google Scholar

Braue JA, Schadt CR, Zwerner JP. 16 - Mycophenolates. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy (Fourth Edition). Elsevier; 2021:178–186.e4.

 Google Scholar

Dupixent® (Dupilumab) Injection [Prescribing Information]. Tarrytown: Regeneron Pharmaceuticals, Inc; 2020.

 Google Scholar

Grinich EE, Simpson EL. 31 - Additional biologic therapeutics: dupilumab, omalizumab, others. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy (Fourth Edition). Elsevier; 2021:339–348.e4.

 Google Scholar