Dupixent PI Flashcards
Dosage in adults and pediatric patients 12+
Initial: 400mg loading + 200mg Q2W
OR
Initial 600mg loading + 300mg Q2W
Dosage for patients with oral corticosteroid-dependent asthma or with co-morbid moderate-to-severe atopic dermatitis or adults with co- morbid chronic rhinosinusitis with nasal polyposis
600mg loading dose + 300mg Q2W
Dosage in pediatric patients
15-30kg: 300mg Q4W
30+ kg: 200mg Q2W
Asthma Indication
DUPIXENT is indicated as:
an add-on maintenance treatment of adult and pediatric patients aged 6 years and older with moderate-to-severe asthma characterized by an eosinophilic phenotype
or
with oral corticosteroid dependent asthma.
DUPIXENT is not indicated for the relief of acute bronchospasm or status asthmaticus.
Mechanism of Action
Dupilumab is a human monoclonal IgG4 antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling by specifically binding to the IL-4Rα subunit shared by the IL-4 and IL-13 receptor complexes.
Dupilumab inhibits IL-4 signaling via the Type I receptor and both IL-4 and IL-13 signaling through the Type II receptor.
Inflammation driven by IL-4 and IL-13 is an important component in the pathogenesis of
asthma, AD, CRSwNP, EoE, and PN.
Multiple cell types that express IL-4Rα (e.g., mast cells, eosinophils, macrophages, lymphocytes, epithelial cells, goblet cells) and inflammatory mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines, chemokines) are involved in inflammation.
Blocking IL-4Rα with dupilumab inhibits IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE. The mechanism of dupilumab action has not been definitively established.
Pharmacodynamics
The median percent reduction from baseline in total IgE concentrations with dupilumab treatments was 52% at Week 24 (DRI12544) and 70% at Week 52 (QUEST).
For FeNO, the mean percent reduction from baseline at Week 2 was 35% and 24% in DRI12544
and QUEST, respectively, and in the overall safety population, the mean FeNO level decreased
to 20 ppb.
Steady State Concentrations
Steady-state concentrations were achieved by Week 16 following the administration of 600 mg starting dose and 300 mg dose either weekly or Q2W, or 400 mg starting dose and 200 mg dose Q2W, or 300 mg Q2W without a loading dose.
Time to non-detectable concentrations
9-13 weeks in adults and peds 12-17
much longer in younger
DRI12544
24-week dose-ranging study
776 adult subjects (18 years of age and older).
The primary endpoint was mean change from baseline to Week 12 in FEV1 (L) in subjects with baseline blood eosinophils ≥300 cells/mcL.
DUPIXENT compared with placebo was evaluated in adult subjects with moderate-to-severe asthma on a medium or high-dose inhaled corticosteroid and a long acting beta agonist.
Subjects were randomized to receive either 200 mg (N=150) or 300 mg (N=157) DUPIXENT
every other week (Q2W) or 200 mg (N=154) or 300 mg (N=157) DUPIXENT every 4 weeks
following an initial dose of 400 mg, 600 mg or placebo (N=158), respectively.
Other endpoints included percent change from baseline in FEV1 and annualized rate of severe asthma exacerbation events during the 24-week placebo-controlled treatment period.
QUEST
52-week study
1902 adult and pediatric subjects (12 years of age
and older).
DUPIXENT compared with placebo was evaluated in 107 pediatric subjects 12 to 17 years of age and 1795 adult subjects with moderate-to-severe asthma on a medium or high-dose inhaled corticosteroid (ICS) and a minimum of one and up to two additional controller
medications.
The primary endpoints were the annualized rate of severe exacerbation events during the 52-week placebo-controlled period and change from baseline in pre-bronchodilator FEV1 at Week 12 in the overall
population (unrestricted by minimum baseline blood eosinophils count).
Subjects were randomized to receive either 200 mg (N=631) or 300 mg (N=633)
DUPIXENT Q2W (or matching placebo for either 200 mg [N=317] or 300 mg [N=321] Q2W)
following an initial dose of 400 mg, 600 mg or placebo, respectively.
Additional secondary endpoints included annualized severe exacerbation rates and FEV1 in subjects with different baseline levels of blood eosinophils as well as responder rates in the ACQ-5 and AQLQ(S)
scores.
VENTURE
24-week
oral corticosteroid-reduction study
210 adult and pediatric subjects 15 years of age and older with asthma who required daily oral corticosteroids in addition to regular use of high dose inhaled corticosteroids plus an additional controller.
After optimizing the OCS dose during the screening period, subjects received 300 mg DUPIXENT (N=103) or placebo (N=107) once Q2W for 24 weeks following an initial dose of 600 mg or placebo.
Subjects continued to receive their existing asthma medicine during the study; however, their
OCS dose was reduced every 4 weeks during the OCS reduction phase (Week 4-20), as long as
asthma control was maintained.
The primary endpoint was the percent reduction of oral corticosteroid dose at Weeks 20 to 24 compared with the baseline dose, while maintaining asthma control in the overall population (unrestricted by minimum baseline blood eosinophils count).
Additional secondary endpoints included the annualized rate of severe exacerbation
events during treatment period and responder rate in the ACQ-5 and AQLQ(S) scores
3 Markers of T2 Inflammation
EOS > 150 cells
IgE > 30 IU/mL
FeNO > 20ppb
Exacerbation Reduction (website)
Up to 81% significant reduction in annualized rate of severe exacerbations through Week 24 (DRI12544)
Lung Function Improvement (website)
Rapid FEV1 improvement at Week 2 and sustained through Week 52 (QUEST)
OCS Reduction / Elimination (website)
86% of patients reduced or eliminated their OCS dose at Week 24 (VENTURE)
