Evaluation of Potential Disease-Mediated Drug-Drug Interaction in Patients With Moderate-to-Severe Atopic Dermatitis Receiving Dupilumab

Clinical Pharmacology and Therapeutics
John D DavisA Thomas DiCioccio

Abstract

This open-label drug-drug interaction study assessed whether blockade by dupilumab of interleukin (IL)-4 and IL-13 signaling affects the pharmacokinetics of drugs metabolized by cytochrome P450 (CYP450) enzymes. The pharmacokinetics of five CYP450 substrates given orally (midazolam, omeprazole, S-warfarin, caffeine, and metoprolol, metabolized by CYP3A, CYP2C19, CYP2C9, CYP1A2, and CYP2D6, respectively) were evaluated before and 28 days after initiation of dupilumab treatment (subcutaneous 300 mg weekly) in 14 patients with moderate-to-severe atopic dermatitis. Dupilumab had no clinically relevant effects on the pharmacokinetics of CYP450 substrates, provided substantial clinical benefit, and was generally well tolerated. Only one serious adverse event was reported, an episode of systemic inflammatory response syndrome that resolved after treatment was discontinued. In summary, blockade of IL-4/IL-13 signaling in patients with type 2 inflammation does not appear to significantly affect CYP450 enzyme activities; the use of dupilumab in atopic dermatitis patients is unlikely to influence the pharmacokinetics of CYP450 substrates.

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Citations

May 31, 2019·Current Opinion in Allergy and Clinical Immunology·Jorien van der SchaftDeepak M W Balak
Mar 29, 2019·American Journal of Clinical Dermatology·Aleksi J HendricksVivian Y Shi
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Jul 17, 2021·Clinical Pharmacology and Therapeutics·Mohamed A KamalJohn D Davis
Oct 5, 2021·Clinical Pharmacology and Therapeutics·Ann-Cathrine Dalgård DunvaldTore B Stage

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Methods Mentioned

BETA
ELISA

Clinical Trials Mentioned

NCT03054428
NCT02379052
NCT02647086
NCT01949311

Software Mentioned

Phoenix WinNonLin

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