Amy S Paller1, Elaine C Siegfried2, Diamant Thaçi3, Andreas Wollenberg4, Michael J Cork5, Peter D Arkwright6, Melinda Gooderham7, Lisa A Beck8, Mark Boguniewicz9, Lawrence Sher10, Jamie Weisman11, John T O'Malley12, Naimish Patel12, Megan Hardin12, Neil M H Graham13, Marcella Ruddy13, Xian Sun13, John D Davis13, Mohamed A Kamal13, Faisal A Khokhar13, David M Weinreich13, George D Yancopoulos13, Bethany Beazley13, Ashish Bansal13, Brad Shumel14. 1. Northwestern University Feinberg School of Medicine, Chicago, Illinois; Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois. 2. Saint Louis University, St. Louis, Missouri; Cardinal Glennon Children's Hospital, St. Louis, Missouri. 3. Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany. 4. Ludwig-Maximilian University, Munich, Germany. 5. University of Sheffield, Sheffield, United Kingdom. 6. Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, United Kingdom. 7. Probity Medical Research, Peterborough, Ontario, Canada; SKiN Centre for Dermatology, Peterborough, Ontario, Canada; Queen's University, Kingston, Ontario, Canada. 8. University of Rochester Medical Center, Rochester, New York. 9. National Jewish Health, Denver, Colorado; University of Colorado School of Medicine, Denver, Colorado. 10. Peninsula Research Associates, Rolling Hills Estates. 11. Advanced Medical Research, PC, Atlanta, California. 12. Sanofi, Cambridge, Massachusetts. 13. Regeneron Pharmaceuticals, Inc, Tarrytown New York. 14. Regeneron Pharmaceuticals, Inc, Tarrytown New York. Electronic address: Brad.shumel@regeneron.com.
Abstract
BACKGROUND:Children with severe atopic dermatitis (AD) have limited treatment options. OBJECTIVE: We report the efficacy and safety of dupilumab + topical corticosteroids (TCS) in children aged 6-11 years with severe AD inadequately controlled with topical therapies. METHODS: In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w, baseline weight <30 kg; 200 mg q2w, baseline weight ≥30 kg), or placebo; with concomitant medium-potency TCS. RESULTS: Both the q4w and q2w dupilumab + TCS regimens resulted in clinically meaningful and statistically significant improvement in signs, symptoms, and quality of life (QOL) versus placebo + TCS in all prespecified endpoints. For q4w, q2w, and placebo, 32.8%, 29.5%, and 11.4% of patients, respectively, achieved Investigator's Global Assessment scores of 0 or 1; 69.7%, 67.2%, and 26.8% achieved ≥75% improvement in Eczema Area and Severity Index scores; and 50.8%, 58.3%, and 12.3% achieved ≥4-point reduction in worst itch score. Response to therapy was weight-dependent: optimal dupilumab doses for efficacy and safety were 300 mg q4w in children <30 kg and 200 mg q2w in children ≥30 kg. Conjunctivitis and injection-site reactions were more common with dupilumab + TCS than with placebo + TCS. LIMITATIONS: Short-term 16-week treatment period; severe AD only. CONCLUSION:Dupilumab + TCS is efficacious and well tolerated in children with severe AD, significantly improving signs, symptoms, and QOL.
RCT Entities:
BACKGROUND:Children with severe atopic dermatitis (AD) have limited treatment options. OBJECTIVE: We report the efficacy and safety of dupilumab + topical corticosteroids (TCS) in children aged 6-11 years with severe AD inadequately controlled with topical therapies. METHODS: In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w, baseline weight <30 kg; 200 mg q2w, baseline weight ≥30 kg), or placebo; with concomitant medium-potency TCS. RESULTS: Both the q4w and q2w dupilumab + TCS regimens resulted in clinically meaningful and statistically significant improvement in signs, symptoms, and quality of life (QOL) versus placebo + TCS in all prespecified endpoints. For q4w, q2w, and placebo, 32.8%, 29.5%, and 11.4% of patients, respectively, achieved Investigator's Global Assessment scores of 0 or 1; 69.7%, 67.2%, and 26.8% achieved ≥75% improvement in Eczema Area and Severity Index scores; and 50.8%, 58.3%, and 12.3% achieved ≥4-point reduction in worst itch score. Response to therapy was weight-dependent: optimal dupilumab doses for efficacy and safety were 300 mg q4w in children <30 kg and 200 mg q2w in children ≥30 kg. Conjunctivitis and injection-site reactions were more common with dupilumab + TCS than with placebo + TCS. LIMITATIONS: Short-term 16-week treatment period; severe AD only. CONCLUSION:Dupilumab + TCS is efficacious and well tolerated in children with severe AD, significantly improving signs, symptoms, and QOL.
Authors: Mohamed A Kamal; John D Davis; Pavel Kovalenko; Kamal Srinivasan; Eric L Simpson; Takeshi Nakahara; Makoto Sugaya; Atsuyuki Igarashi; Marius Ardeleanu; Christine Xu; Kazuhiko Arima Journal: Clin Transl Sci Date: 2022-08-20 Impact factor: 4.438
Authors: Jerry Bagel; Tien Q Nguyen; Hermenio Lima; Neal Jain; David M Pariser; Sylvia Hsu; Gil Yosipovitch; Haixin Zhang; Jingdong Chao; Shikha Bansal; Zhen Chen; Daniel Richman; Andrew Korotzer; Marius Ardeleanu Journal: Dermatol Ther (Heidelb) Date: 2022-05-20
Authors: Jonathan I Silverberg; Eric L Simpson; Mark Boguniewicz; Marjolein S De Bruin-Weller; Peter Foley; Yoko Kataoka; Gaëlle Bégo-Le-Bagousse; Zhen Chen; Brad Shumel; Jingdong Chao; Ana B Rossi Journal: Acta Derm Venereol Date: 2021-11-10 Impact factor: 3.875
Authors: Mohamed A Kamal; Pavel Kovalenko; Matthew P Kosloski; Kamal Srinivasan; Yi Zhang; Manoj Rajadhyaksha; Ching-Ha Lai; Vanaja Kanamaluru; Christine Xu; Xian Sun; Eric L Simpson; Amy S Paller; Elaine C Siegfried; Brad Shumel; Ashish Bansal; Nidal Al-Huniti; John D Davis Journal: Clin Pharmacol Ther Date: 2021-08-24 Impact factor: 6.903