Dupi in AD in adolescence
Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Atopic Dermatitis
TAKE-HOME MESSAGE
- This phase III randomized, double-blind, placebo-controlled trial included 251 patients aged 12 to 18 years with moderate to severe atopic dermatitis. Participants were randomized to either dupilumab every 2 weeks (n=82), dupilumab every 4 weeks (n=84), or placebo (n=85). In total, 240 patients completed the 16-week study. Primary endpoints included the proportion of patients to reach EASI-75 and IGA 0 or 1 at week 16.
- The highest proportion of patients to achieve EASI-75 was in the every-2-week group (41.5%), followed by the every-4-week group (38.1%) versus placebo (8.2%). Similarly, a higher proportion of patients in the every-2-week group (24.4%) reached IGA 0 or 1 compared with the every-4-week group (17.9%) and placebo (2.4%). Every-2-week dosing was also more effective than every-4-week dosing and placebo in terms of measured secondary outcomes. Dupilumab was found to improve asthma control and suppress IgE concentrations of specific food and aeroallergens as well.
– Caitlyn T. Reed, MD
- Written by
IMPORTANCE
Adolescents with atopic dermatitis (AD) have high disease burden negatively affecting quality of life, with limited treatment options. The efficacy and safety of dupilumab, a monoclonal antibody, approved for treatment in adolescent patients with inadequately controlled AD, remain unknown in this patient population.
OBJECTIVE
To assess the efficacy and safety of dupilumab monotherapy in adolescents with moderate to severe inadequately controlled AD.
DESIGN, SETTING, AND PARTICIPANTS
A randomized, double-blind, parallel-group, phase 3 clinical trial was conducted at 45 US and Canadian centers between March 21, 2017, and June 5, 2018. A total of 251 adolescents with moderate to severe AD inadequately controlled by topical medications or for whom topical therapy was inadvisable were included.
INTERVENTIONS
Patients were randomized (1:1:1; interactive-response system; stratified by severity and body weight) to 16-week treatment with dupilumab, 200 mg (n = 43; baseline weight <60 kg), or dupilumab, 300 mg (n = 39; baseline weight 60 kg), every 2 weeks; dupilumab, 300 mg, every 4 weeks (n = 84); or placebo (n = 85).
MAIN OUTCOMES AND MEASURES
Proportion of patients with 75% or more improvement from baseline in Eczema Area and Severity Index (EASI-75) (scores range from 0 to 72, with higher scores indicating greater severity) and Investigator's Global Assessment (IGA) 0 or 1 on a 5-point scale (scores range from 0 to 4, with higher scores indicating greater severity) at week 16.
RESULTS
A total of 251 patients were randomized (mean [SD] age, 14.5 [1.7] years; 148 [59.0%] male). Of 250 patients with data available on concurrent allergic conditions, most had comorbid type 2 diseases (asthma, 134 [53.6%]; food allergies, 60.8%; allergic rhinitis, 65.6%). A total of 240 patients (95.6%) completed the study. Dupilumab achieved both coprimary end points at week 16. The proportion of patients with EASI-75 improvement from baseline increased (every 2 weeks, 41.5%; every 4 weeks, 38.1%; placebo, 8.2%) with differences vs placebo of 33.2% (95% CI, 21.1%-45.4%) for every 2 weeks and 29.9% (95% CI, 17.9%-41.8%) for every 4 weeks (P < .001). Efficacy of the every-2-week regimen was generally superior to the every-4-week regimen. Patients in the dupilumab arms had higher percentage values of conjunctivitis (every 2 weeks, 9.8%; every 4 weeks, 10.8%; placebo, 4.7%) and injection-site reactions (every 2 weeks, 8.5%; every 4 weeks, 6.0%; placebo, 3.5%), and lower nonherpetic skin infections (every 2 weeks, 9.8%; every 4 weeks, 9.6%; placebo, 18.8%).
CONCLUSIONS AND RELEVANCE
In this study, dupilumab significantly improved AD signs, symptoms, and quality of life in adolescents with moderate to severe AD, with an acceptable safety profile. Placebo-corrected efficacy and safety of dupilumab were similar in adolescents and adults.
Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis: A Phase 3 Randomized Clinical Trial
JAMA Dermatol 2019 Nov 06;[EPub Ahead of Print], EL Simpson, AS Paller, EC Siegfried, M Boguniewicz, L Sher, MJ Gooderham, LA. Beck, E Guttman-Yassky, D Pariser, A Blauvelt, J Weisman, B Lockshin, T Hultsch, Q Zhang, MA Kamal, JD Davis, B Akinlade, H Staudinger, JD Hamilton, NMH Graham, G Pirozzi, A Gadkari, L Eckert, N Stahl, GD Yancopoulos, M Ruddy, A BansalSkin Care Physicians of Costa Rica
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posted by dermatica at
December 30, 2019
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0 Comments
These authors publish reassuring evidence on the safety and efficacy of dupilumab in adolescents with moderate/severe atopic dermatitis (AD). A total of 240 patients (mean age of 14.5 years) completed this 16-week study, with improvement in all measured outcomes and side effects similar to those reported in other studies, including conjunctivitis and injection site reactions. Different time intervals (every 2 weeks and every 4 weeks) were investigated in this study. Outcomes with every 2–week dosing were more favorable.
Dupilumab was approved for use in adolescents aged 12-to 17 years in March of this year. As many pediatric dermatologists get accustomed to prescribing this and following these patients, we are reassured of efficacy and short-term safety by studies like this. I remain hopeful for an expanded indication in the future for younger children with severe AD. This drug is a rare game-changer for patients with severe AD, and the future looks good for continued development and approval of other systemic agents for this impactful disease.