Eric L Simpson1, Thomas Bieber1, Emma Guttman-Yassky1, Lisa A Beck1, Andrew Blauvelt1, Michael J Cork1, Jonathan I Silverberg1, Mette Deleuran1, Yoko Kataoka1, Jean-Philippe Lacour1, Külli Kingo1, Margitta Worm1, Yves Poulin1, Andreas Wollenberg1, Yuhwen Soo1, Neil M H Graham1, Gianluca Pirozzi1, Bolanle Akinlade1, Heribert Staudinger1, Vera Mastey1, Laurent Eckert1, Abhijit Gadkari1, Neil Stahl1, George D Yancopoulos1, Marius Ardeleanu1. 1. From the Department of Dermatology, Oregon Health and Science University (E.L.S.), and Oregon Medical Research Center (A.B.) - both in Portland; the Department of Dermatology and Allergy, University of Bonn, Bonn (T.B.), the Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin (M.W.), and the Department of Dermatology and Allergy, Ludwig-Maximilian University, Munich (A.W.) - all in Germany; the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York (E.G.-Y.), the Department of Dermatology, University of Rochester Medical Center, Rochester (L.A.B.), and Regeneron Pharmaceuticals, Tarrytown (Y.S., N.M.H.G., B.A., V.M., A.G., N.S., G.D.Y., M.A.) - all in New York; the Dermatology Research Unit, University of Sheffield Medical School, Sheffield, United Kingdom (M.J.C.); the Department of Dermatology, Preventive Medicine and Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago (J.I.S.); the Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark (M.D.); the Department of Dermatology, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Osaka, Japan (Y.K.); the Department of Dermatology, University Hospital of Nice, Nice (J.-P.L.), and Sanofi, Chilly-Mazarin (L.E.) - both in France; the Clinic of Dermatology, Tartu University Hospital, Tartu, Estonia (K.K.); the Department of Medicine, Université Laval, Hôpital Hôtel-Dieu de Québec, Quebec, QC, Canada (Y.P.); and Sanofi, Bridgewater, NJ (G.P., H.S.).
Abstract
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 .).
RCT Entities:
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 .).
Authors: Lynn E Macdonald; Karoline A Meagher; Matthew C Franklin; Natasha Levenkova; Johanna Hansen; Ashok T Badithe; Maggie Zhong; Pamela Krueger; Ashique Rafique; Naxin Tu; James Shevchuk; Saurabh Wadhwa; George Ehrlich; Joannie Bautista; Craig Grant; Lakeisha Esau; William T Poueymirou; Wojtek Auerbach; Lori Morton; Robert Babb; Gang Chen; Tammy Huang; Douglas MacDonald; Kenneth Graham; Cagan Gurer; Vera A Voronina; John R McWhirter; Chunguang Guo; George D Yancopoulos; Andrew J Murphy Journal: Proc Natl Acad Sci U S A Date: 2019-12-26 Impact factor: 11.205