Dupilumab treatment results in early and sustained improvements in itch in adolescents and adults with moderate to severe atopic dermatitis: Analysis of the randomized phase 3 studies SOLO 1 and SOLO 2, AD ADOL, and CHRONOS - 15/04/20
, Gil Yosipovitch, MD b, Eric L. Simpson, MD, MCR c, Brian S. Kim, MD d, Jashin J. Wu, MD e, Laurent Eckert, PhD f, Isabelle Guillemin, MD, PhD g, Zhen Chen, PhD, MS, MA h, Marius Ardeleanu, MD h, Ashish Bansal, MD, MBA h, Mandeep Kaur, MD, MS i, Ana B. Rossi, MD i, Neil M.H. Graham, MD, MBBS, MPH h, Naimish Patel, MD j, Abhijit Gadkari, PhD hAbstract |
Background |
Pruritus (itch) is a cardinal symptom in atopic dermatitis (AD).
Objective |
To evaluate the timing and effect of dupilumab on itch.
Methods |
Analysis of data from 1505 patients with moderate to severe AD included in 4 randomized controlled studies, treated for up to 52 weeks. Adults received dupilumab 300 mg every 2 weeks or placebo monotherapy (SOLO 1: NCT02277743; SOLO 2: NCT02277769), with concomitant topical corticosteroids (CHRONOS: NCT02260986); adolescents (≥12 to <18 y) were treated with dupilumab monotherapy every 2 weeks (200 mg for baseline weight of <60 kg; 300 mg for baseline weight of ≥60 kg) or placebo (AD ADOL: NCT03054428).
Results |
Dupilumab showed significant rapid improvements from baseline in daily Peak Pruritus Numerical Rating Scale scores versus placebo, by day 2 in adults and day 5 in adolescents. At treatment end, dupilumab vs placebo/control had greater least-squares mean percent change from baseline in the weekly average of Peak Pruritus Numerical Rating Scale scores: SOLO −47.5% vs −20.5%; AD-ADOL −47.9% vs −19.0%; CHRONOS −57.3% vs −30.9% (P < .0001 for all).
Limitations |
Short duration of monotherapy trials (16 weeks).
Conclusion |
Across 4 randomized trials, dupilumab treatment showed rapid and sustained improvements in the magnitude of itch, starting with first dose; responses progressively increased and were sustained through to the end of treatment, up to 1 year.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : adolescents, adults, atopic dermatitis, CHRONOS, dupilumab, itch, LIBERTY, SOLO
Plan
| Funding sources: Sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing and editorial assistance was provided by Grace Richmond, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals. |
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| Disclosure: Dr Silverberg has been an investigator for AbbVie, AnaptysBio, Arena, Asana, Boehringer Ingelheim, Dermira, Dermavant, DS Biopharma, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Kiniksa, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, and Sanofi; a consultant for AbbVie, Eli Lilly, Galderma, Incyte, Kiniksa, LEO Pharma, Menlo Therapeutics, Pfizer, Realm, Regeneron Pharmaceuticals, Inc, and Sanofi; and a speaker for Regeneron Pharmaceuticals, Inc, and Sanofi. Dr Yosipovitch has been an advisory board member for AbbVie, Bayer, CeraVe, Eli Lilly, Galderma, Kiniksa, Menlo Therapeutics, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi, Sienna, and Trevi; and has received grants/research funding from Kiniksa, LEO Pharma, Pfizer, and Sun. Dr Simpson has been a consultant for AbbVie, Anacor, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, LEO Pharma, MedImmune, Menlo Therapeutics, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi, and Valeant Pharmaceuticals North America; and has received grants/research funding from Amgen, Anacor, Celgene, Chugai, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, MedImmune, Novartis, Pfizer, Regeneron Pharmaceuticals, Roivant, Sanofi, Tioga, and Vanda. Dr Kim has been a consultant for AbbVie, Concert, Incyte, Menlo Therapeutics, and Pfizer; served on the advisory board for Celgene, Kiniksa, Menlo Therapeutics, Regeneron Pharmaceuticals, Inc, Sanofi, and Theravance Biopharma; holds stock in Gilead Sciences and Mallinckrodt; is the founder and chief scientific officer of Nuogen; and has received funding for research in the Kim laboratory from Celgene and LEO Pharma. Dr Wu has been an investigator for AbbVie, Amgen, Eli Lilly, Janssen, and Novartis; a consultant for AbbVie, Almirall, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Dr Reddy's Laboratories, Eli Lilly, Janssen, LEO Pharma, Novartis, Promius Pharma, Regeneron Pharmaceuticals, Inc, Sun Pharmaceutical, UCB, and Valeant Pharmaceuticals North America; and a speaker for AbbVie, Celgene, Novartis, Regeneron Pharmaceuticals, Inc, Sanofi Genzyme, Sun Pharmaceutical, UCB, and Valeant Pharmaceuticals North America. Drs Eckert, Guillemin, and Patel are employees of Sanofi and may hold stock and/or stock options in the company. Drs Chen, Ardeleanu, Bansal, Graham, and Gadkari are employees and shareholders of Regeneron Pharmaceuticals, Inc. Drs Kaur and Rossi are employees of Sanofi Genzyme and may hold stock and/or stock options in the company. |
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| IRB approval status: Details of all 4 studies (SOLO 1 and 2: NCT02277743 and NCT02277769; CHRONOS: NCT02260986; AD ADOL: NCT03054428), along with primary efficacy and safety results, have been previously reported. All study documents and procedures were approved by the appropriate institutional review boards/ethics committees at each study site. |
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