Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Eucrisa™ - Crisaborole Manufacturer: Anacor Pharmaceuticals, Inc. FDA Approval Date: 12/14/2016 Maria Buckner, PharmD Candidate Eucrisa™ - crisaborole Objectives • At the end of this presentation participants will be able to: 1. Appropriately recommend Eucrisa™ - (crisaborole) 2. Effectively educate patients on the purpose, proper use and potential adverse effects of Eucrisa™ (crisaborole) Eucrisa™ - crisaborole Clinical Application • Indications: • Topical treatment of mild to moderate atopic dermatitis (AD) in patients 2 years of age and older • Place in therapy: • First line option in place of topical steroids and calcineurin inhibitors for the treatment of mild to moderate AD Eucrisa [package insert]. Eucrisa™ - crisaborole Clinical Application • Contraindications: • Known hypersensitivity • Warnings: • None • Precautions: • None Eucrisa [package insert]. Eucrisa™ - crisaborole Clinical Application • Pregnancy: • No human data available • No adverse effects seen with oral administration of up to 600 mg/kg/day in rat and rabbit studies • Lactation: • No human data available Eucrisa [package insert]. Eucrisa™ - crisaborole Drug Facts • Pharmacology: • Topical phosphodiesterase 4 (PDE-4) inhibitor • PDE-4 inhibition results in increased intracellular cAMP levels • Exact mechanism is not well defined but is thought to work by reducing pro-inflammatory cytokines thought to cause signs and symptoms of AD Eucrisa [package insert]. Eucrisa™ - crisaborole Drug Facts • Pharmacokinetics: A Limited; systemic concentrations at steady state (Cmax) on Day 8 D 97% bound to human plasma proteins M Metabolized into 2 inactive metabolites via hydrolysis and oxidation E Renal excretion of metabolites Eucrisa [package insert]. Eucrisa™ - crisaborole Drug Interactions • Drug Interactions – Object Drugs: • Weak inhibitor of CYP1A2 and 2B6 • Moderate inhibitor of CYP2C8 and 2C9 • Trial with warfarin as CYP2C9 substrate showed no drug interaction potential Eucrisa [package insert]. Eucrisa™ - crisaborole Drug Interactions • Drug Interactions – Precipitant Drugs: • None identified Eucrisa [package insert]. Eucrisa™ - crisaborole Adverse Effects • Common Adverse Effects: (crisaborole%) [placebo%] • Application site pain (4%) [1%] • Serious Adverse Effects: • None Eucrisa [package insert]. Eucrisa™ - crisaborole Monitoring Parameters • Efficacy Monitoring: • Clearing/improvement of AD from baseline • Toxicity Monitoring: • Very limited systemic exposure • Inactive metabolites result in low risk of toxicity • Theoretically, extremely high systemic concentrations can lead to GI toxicities Eucrisa [package insert]. Eucrisa™ - crisaborole Prescription Information • Dosing: Twice daily application of 2% topical ointment in a thin layer to affected areas • Cost: – Not yet available Eucrisa [package insert]. Eucrisa™ - crisaborole Literature Review • Efficacy and safety of crisaborole ointment for the topical treatment of AD in children and adults (AD-301 and AD-302) • Study Design • Two identically designed, vehicle-controlled, randomized, double-blind phase 3 trials • Patient assigned 2:1 to crisaborole or vehicle treatment twice daily for 28 days • N=1522 between both studies Paller AS, et al. J Am Acad Dermatol. 2016;75:494-503.e4. Eucrisa™ - crisaborole Literature Review Inclusion Criteria • Age 2 years and older • Clinical diagnosis of AD • 5% or more treatable body surface area involvement • Baseline ISGA score of mild (2) or moderate (3) Exclusion Criteria • Previous use of biologic therapy or systemic corticosteroids within 28 days • Topical corticosteroid or topical calcineurin inhibitor use within 14 days • Active skin infection Paller AS,et al. J Am Acad Dermatol. 2016;75:494-503.e4. Eucrisa™ - crisaborole Literature Review • Patient Characteristics AD-301 AD-302 Crisaborole n=503 Vehicle n=256 Crisaborole n=513 Vehicle n=250 Mean Age 12.0 12.4 12.6 11.8 Age Range 2-65 2-63 2-79 2-79 Sex, % Male Female 43.5 56.5 44.1 55.9 45.0 55.0 44.8 55.2 Baseline ISGA, % Mild (2) Moderate (3) 39.0 61.0 36.3 63.7 38.4 61.6 40.0 60.0 % BSA, mean 18.8 18.6 17.9 17.7 Characteristic % BSA, range 5-95 5-90 5-95 5-90 Paller AS, et al. J Am Acad Dermatol. 2016;75:494-503.e4. Eucrisa™ - crisaborole Literature Review • Primary Efficacy Endpoint • Success in ISGA score at day 29 defined as clear (0) or almost clear (1) with a 2grade or more improvement from baseline • Secondary Efficacy Endpoint • Pruritus severity • Primary Safety Endpoint • Treatment related adverse events Paller AS, et al. J Am Acad Dermatol. 2016;75:494-503.e4. Eucrisa™ - crisaborole Literature Review • Efficacy Results • Clear/almost clear with ≥ 2-grade improvement (primary) • AD-301: 32.8% vs 254.%, P = 0.038 • AD-302: 31.4% vs 18.0%, P < 0.001 • Improvement in pruritus (secondary) • Pooled data, days 8,15,22: P < 0.001; day 29: P = 0.002 • Safety Result • Application site pain (4.4%) [1.2%] Paller AS, et al. J Am Acad Dermatol. 2016;75:494-503.e4. Eucrisa™ - crisaborole Literature Review • Conclusions • Crisaborole is a promising new option for mild to moderate AD targeting the underlying mechanism of the disease • Improvement was seen in all efficacy measures over vehicle alone including pruritus • Crisaborole has a favorable safety profile with low incidence of adverse effects Paller AS, et al. J Am Acad Dermatol. 2016;75:494-503.e4. Eucrisa™ - crisaborole Summary • Eucrisa ™ (crisaborole) is a non-steroidal, topical anti-inflammatory PDE-4 inhibitor ointment for the treatment of mild to moderate atopic dermatitis in patients ≥ 2 • A thin layer should be applied to the affected area BID • The most common side effect is burning or stinging at the application site • Eucrisa ™ has low systemic absorption, quick metabolism and a low rate of adverse effects, making it a safe alternative topical steroids and calcineurin inhibitors for the treatment of mild to moderate AD Eucrisa™ - crisaborole References 1. www.myeucrisa.com 2. Eucrisa [package insert]. Palo Alto, CA: Anacor Pharmaceuticals Inc.; 2016. 3. Include ALL article references in standard format: Paller AS, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 inhibitor for the topical treatment of atopic dermatitis in children and adults. J Am Acad Dermatol. 2016;75:494-503.e4.