14
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis : A Phase 3 Randomized Clinical Trial

      research-article
      , MD 1 , , MS, MD 2 , 3 , , MD 4 , , MD 5 , , MD 6 , , MD 7 , 8 , 9 , , MD 10 , , MD, PhD 11 , 12 , 13 , , MD 14 , , MD, MBA 15 , , MD 16 , , MD 17 , 18 , , MD 19 , , PhD 20 , , PharmD, PhD 20 , , PhD 20 , , MD, MBA 20 , , MD, PhD 21 , , PhD 20 , , MBBS, MD, MPH 20 , , MD, PhD 21 , , PhD 20 , , PhD 22 , , PhD 20 , , MD, PhD 20 , , MD 20 , , MD 20 ,
      JAMA Dermatology
      American Medical Association

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Key Points

          Question

          What is the efficacy and safety of dupilumab monotherapy in adolescents with moderate to severe inadequately controlled atopic dermatitis?

          Findings

          In this randomized phase 3 clinical trial including 251 adolescents with moderate to severe atopic dermatitis, dupilumab 200 or 300 mg every 2 weeks and 300 mg every 4 weeks resulted in a significant treatment response vs placebo following 16-week treatment, with an acceptable safety profile.

          Meaning

          The findings appear to support the use of dupilumab for the treatment of adolescents with moderate to severe atopic dermatitis.

          Abstract

          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.

          Trial Registration

          ClinicalTrials.gov identifier: NCT03054428

          Abstract

          This phase 3 randomized clinical trial evaluates the efficacy and safety of 2 dose regimens of dupilumab for treatment of moderate to severe atopic dermatitis in adolescents.

          Related collections

          Most cited references35

          • Record: found
          • Abstract: not found
          • Article: not found

          World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.

          (2013)
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma

            Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

              Background Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. Methods In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment and a reduction of 2 points or more in that score from baseline at week 16. Results We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups. Conclusions In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743 ; SOLO 2 ClinicalTrials.gov number, NCT02277769 .).
                Bookmark

                Author and article information

                Journal
                JAMA Dermatol
                JAMA Dermatol
                JAMA Dermatology
                American Medical Association
                2168-6068
                2168-6084
                6 November 2019
                January 2020
                6 November 2019
                : 156
                : 1
                : 44-56
                Affiliations
                [1 ]Department of Dermatology, Oregon Health & Science University, Portland
                [2 ]Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
                [3 ]Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois
                [4 ]Department of Pediatrics, School of Medicine, Saint Louis University, St. Louis, Missouri
                [5 ]Department of Pediatrics, National Jewish Health and University of Colorado School of Medicine, Denver
                [6 ]Peninsula Research Associates, Rolling Hills Estates, California
                [7 ]Skin Centre for Dermatology, Peterborough, Ontario, Canada
                [8 ]Department of Medicine, Queen's University, Kingston, Ontario, Canada
                [9 ]Probity Medical Research, Waterloo, Ontario, Canada
                [10 ]Department of Dermatology, University of Rochester Medical Center, Rochester, New York
                [11 ]Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York
                [12 ]Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York
                [13 ]Laboratory for Investigative Dermatology, Rockefeller University, New York, New York
                [14 ]Department of Dermatology, Eastern Virginia Medical School, Norfolk
                [15 ]Oregon Medical Research Center, Portland
                [16 ]Advanced Medical Research, Atlanta, Georgia
                [17 ]US Dermatology Partners, Rockville, Maryland
                [18 ]Georgetown University, Washington, District of Columbia
                [19 ]Sanofi Genzyme, Cambridge, Massachusetts
                [20 ]Regeneron Pharmaceuticals Inc, Tarrytown, New York
                [21 ]Sanofi, Bridgewater, New Jersey
                [22 ]Sanofi, Chilly-Mazarin, France
                Author notes
                Article Information
                Accepted for Publication: August 30, 2019.
                Published Online: November 6, 2019. doi:10.1001/jamadermatol.2019.3336
                Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. © 2019 Simpson EL et al. JAMA Dermatology.
                Corresponding Author: Ashish Bansal, MD, Regeneron Pharmaceuticals Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 ( ashish.bansal@ 123456regeneron.com ).
                Author Contributions: Dr Simpson had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Simpson, Paller, Hultsch, Davis, Akinlade, Staudinger, Graham, Pirozzi, Eckert, Yancopoulos, Bansal.
                Acquisition, analysis, or interpretation of data: All authors.
                Drafting of the manuscript: Simpson, Paller, Boguniewicz, Hultsch, Zhang, Kamal, Davis, Akinlade, Hamilton, Graham, Bansal.
                Critical revision of the manuscript for important intellectual content: Simpson, Paller, Siegfried, Boguniewicz, Sher, Gooderham, Beck, Guttman-Yassky, Pariser, Blauvelt, Weisman, Lockshin, Hultsch, Zang, Kamal, Davis, Akinlade, Staudinger, Hamilton, Pirozzi, Gadkari, Eckert, Stahl, Yancopoulos, Ruddy, Bansal.
                Statistical analysis: Siegfried, Sher, Hultsch, Zhang, Akinlade, Bansal.
                Obtained funding: Graham, Pirozzi.
                Administrative, technical, or material support: Siegfried, Beck, Davis, Akinlade, Hamilton, Graham.
                Supervision: Paller, Siegfried, Guttman-Yassky, Blauvelt, Lockshin, Hultsch, Davis, Staudinger, Graham, Pirozzi, Gadkari, Bansal.
                Conflict of Interest Disclosures: Dr Simpson reports receiving personal fees from AbbVie, Boehringer-Ingelheim, Dermavant, Dermira, Galderma, GlaxoSmithKline, Incyte, LEO Pharma, Lilly, Menlo Therapeutics, Pfizer Inc, Pierre Fabre Dermo Cosmetique, Regeneron Pharmaceuticals Inc, Sanofi Genzyme, and Valeant Pharmaceutical Co; receiving grants from AbbVie, Celgene, Dermira, Galderma, Leo Pharma, Lilly, Pfizer, Regeneron Pharmaceuticals Inc, Roivant, Sanofi Genzyme; and receiving nonfinancial support from Regeneron Pharmaceuticals Inc and Sanofi Genzyme. Dr Paller reports receiving honoraria as a consultant for AbbVie, Amgen, Asana, Boehringer Ingelheim, Celgene, Dermavant, Dermira Pharmaceutical Co, Forte, Galderma, Incyte, LEO Pharma, Lilly, Matrisys, Menlo Therapeutics, Morphosys/Galapagos, Novan, Novartis, Pfizer, Regeneron Pharmaceuticals Inc, Sanofi, and UCB, and receiving grants from AbbVie, Anaptysbio, Galderma, Incyte, LEO Pharma, Janssen, Lilly, Novartis, and Regeneron Pharmaceuticals Inc. Dr Siegfried reports receiving personal fees and honoraria as a consultant and speaker for Regeneron Pharmaceuticals Inc and Sanofi, receiving consulting fees and honoraria as a consultant, speaker, teacher, and advisory board member for Verrica, receiving consulting fees as an advisory board member from Leo Pharma, Novan, Pierre Fabre, and UCB, receiving consulting fees from Pfizer as a speaker, and receiving grants as a principal investigator for clinical trials paid to her institution from Janssen, Lilly, and Regeneron Pharmaceuticals Inc. Dr Boguniewicz reports receiving grants from Regeneron Pharmaceuticals Inc and personal fees as a consultant and speaker for Regeneron Pharmaceuticals Inc and Sanofi Genzyme. Dr Sher reports receiving study grants from Regeneron Pharmaceuticals Inc and Sanofi Genzyme. Dr Gooderham reports being an investigator, speaker, advisor, or consultant for AbbVie, Akros, Amgen, Arcutis, BMS, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Roche, Regeneron Pharmaceuticals Inc, Sanofi Genzyme, Sun Pharma, UCB, and Valeant. Dr Beck reports receiving personal fees as a consultant from AbbVie, Allakos, Arena Pharma, Astra-Zeneca, Connect Biopharma, Incyte, LEO Pharma, Lilly, Novan, Novartis, Pfizer, Regeneron., Sanofi, and UCB; receiving compensation as a principal investigator from her institution for trials funded by AbbVie, Leo Pharma, Pfizer, and Regeneron; and holding Pfizer and Medtronics stock. Dr Guttman-Yassky reports receiving personal fees from AbbVie, Allergan, Amgen, Asana Biosciences, Boehringer-Ingelheim, Cara Therapeutics, Celgene, Concert, DBV, Dermavant, Dermira, DS Biopharma, EMD Serono, Escalier, Flx Bio, Galderma, Glenmark, Incyte, Kyowa Kirin, LEO Pharma, Lilly, Mitsubishi Tanabe, Novan, Novartis, Pfizer, Regeneron Pharmaceuticals Inc, Sanofi, Sienna Biopharmaceuticals, and Union Therapeutics, and grants from AbbVie, Anaptysbio, Asana Biosciences, Boehringer-Ingelheim, Celgene, Dermavant, DS Biopharma, Galderma, Glenmark, Innovaderm, Janssen, Kiniska, LEO Pharma, Lilly, Novan, Novartis, Pfizer, Ralexar, Regeneron Pharmaceuticals Inc, UCB, and Union Therapeutics. Dr Pariser reports receiving grants as an investigator for Regeneron Pharmaceutical Inc and Sanofi and receiving honoraria as an advisory board consultant for Regeneron Pharmaceuticals Inc and Sanofi. Dr Blauvelt reports receiving compensation as an investigator and personal fees as a consultant for AbbVie, Dermira, LEO Pharma, Pfizer, Regeneron Pharmaceuticals Inc, and Sanofi. Dr Weisman reports receiving grants from AbbVie, Allergan, Celgene, Dermira, Galderma, Janssen, LEO Pharma, Lilly, Merck, Novartis, Pfizer, and Regeneron Pharmaceuticals Inc, and personal fees from AbbVie, Lilly, Novartis, and Regeneron Pharmaceuticals Inc. Dr Lockshin reports receiving grants as a clinical investigator for AbbVie, Galderma, Incyte, Lilly, Pfizer, Regeneron Pharmaceuticals Inc, and Sanofi Genzyme, and honoraria from AbbVie, Galderma, Incyte, Lilly, Pfizer, Regeneron Pharmaceuticals Inc, and Sanofi Genzyme. Drs Hultsch, Staudinger, Pirozzi, and Eckert report being employees and holding stock and/or stock options in Sanofi. Drs Zhang, Kamal, Davis, Akinlade, Graham, Gadkari, Stahl, Ruddy, and Bansal report being employees and shareholders of Regeneron Pharmaceuticals Inc. Dr Hamilton reports being an employee and shareholder of Regeneron Pharmaceuticals Inc and having patents planned, pending, or issued broadly relevant to the work. Dr Yancopoulos reports being an employee, shareholder, president, and member of board of directors of Regeneron Pharmaceuticals Inc and having patents pending or issued broadly relevant to the work.
                Funding/Support: This research was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Medical writing and editorial assistance were provided by Jamie Lim, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals Inc. There was no financial compensation outside of salary.
                Role of the Funder/Sponsor: The funders participated in the conception and design of the study, analysis and interpretation of the data, drafting and critical revision of the report, and gave approval to submit.
                Data Sharing Statement: See Supplement 3.
                Additional Contributions: Elizabeth Bucknam, BS, Steve Chen, MS, Mbole Ekaney, PhD, Pavel Kovalenko, PhD, Jacqueline Kuritzky, MA, Nelson Rita, BA, George Vlamis, BS, Linda Williams, RPh, Yi Zhang, PhD, and Xiaoping (Jenny) Zhu, PhD (Regeneron Pharmaceuticals Inc); and El-Bdaoui Haddad, PhD, and Elizabeth Laws, PhD (Sanofi), contributed to the study. No compensation was received.
                Article
                doi190057
                10.1001/jamadermatol.2019.3336
                6865265
                31693077
                622b43ff-1471-42d3-b160-8ba705fdb57a
                Copyright 2019 Simpson EL et al. JAMA Dermatology.

                This is an open access article distributed under the terms of the CC-BY-NC-ND License.

                History
                : 19 April 2019
                : 30 August 2019
                Categories
                Research
                Research
                Original Investigation
                Featured
                Online First
                Comments

                Comments

                Comment on this article