Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis
Eric L Simpson, Thomas Bieber, Emma Guttman-Yassky, Lisa A Beck, Andrew Blauvelt, Michael J Cork, Jonathan I Silverberg, Mette Deleuran, Yoko Kataoka, Jean-Philippe Lacour, Külli Kingo, Margitta Worm, Yves Poulin, Andreas Wollenberg, Yuhwen Soo, Neil M H Graham, Gianluca Pirozzi, Bolanle Akinlade, Heribert Staudinger, Vera Mastey, Laurent Eckert, Abhijit Gadkari, Neil Stahl, George D Yancopoulos, Marius Ardeleanu, SOLO 1 and SOLO 2 Investigators, Elmira Nikolova-Pavlova, Boyka Stoyanova, Tzetza Vlaeva, Afsaneh Alavi, Gail Gauvreau, Sam Henein, Elena Poulos, William Yang, France Lepage, Marni Wiseman, Robert Bissonnette, Tove Agner, Mette Deleuran, Gregor Jemec, Lone Skov, Külli Kingo, Pille Konno, Kristi Pender, Airi Põder, Ave Vahlberg, Risto Oksman, Rafael Pasternack, Anita Remitz, Thomas Bieber, Rolf Dominicus, Beatrice Gerlach, Bernd Kardorff, Andreaa Laura Toader, Andreas Kleinheinz, Sylke Gellrich, Katharina Kreutzer, Nicolas Leitz, Michael Offers, Sylvia Pauser, Marc Radtke, Evelin Roloff, Thomas Rosenbach, Beate Schwarz, Sabine Sell, Jan-Christoph Simon, Petra Staubach, Ulrich Stefan Weigel, Thomas Werfel, Johannes Wohlrab, Andreas Wollenberg, Christoph Rothenberger, Alexandra Walter, Amir Yazdi, Michiko Aihara, Michihiro Hide, Yoko Kataoka, Norito Katoh, Makoto Kawashima, Satomi Kobayashi, Hiroshi Mitsui, Takeshin Nakahara, Hidehisa Saeki, Hirohiko Sueki, Satoru Arai, Masanori Ikeda, Kenji Kabashima, Yasuhiro Kawachi, Akihiro Kume, Shinichi Moriwaki, Yohei Natsuaki, Fuyuki Ogata, Tokuya Omi, Mariko Seishima, Makoto Sugaya, Katsuhiko Tsukamoto, Daisuke Tsuruta, Shoko Urano, Daisuke Watanabe, Akira Yoshioka, Fukumi Furukawa, Atsuko Katoh, Chia Chun Ang, Derrick Chen Wee Aw, Mark Tang, Haur Yueh Lee, Francesc Bordas Orpinell, Gregorio Carretero Hernández, Pablo De La Cueva, Carlos Ferrándiz Foraster, Pilar Iranzo, Anna Jucgla Serra, Pedro Lloret Luna, Servando Marrón Moya, David Moreno Ramírez, Javier Pedraz Muñoz, José Sánchez Carazo, Weily Soong, Cheryl Hull, Sandra Johnson, Neal Bhatia, Marketa Limova, Marina Raikhel, Lawrence Sher, Howard Sofen, Sheldon Spector, Ricardo Tan, Paul Yamauchi, Richard Weber, Stephen Kimura, Christopher Nelson, Shahid Randhawa, Marta Rendon, Miguel Trevino, Mark Ling, Zakiya Rice, Jonathan Silverberg, Dareen Siri, Scott Fretzin, Joseph F Fowler, Erin Boh, Joseph Merola, George Murakawa, Phillip Korenblat, James Campbell, Jerry Bagel, Lisa Beck, Carole Hazan, Robert Kalb, Christopher Smith, Jose Bardelas, Sandra Gawchik, Eric Schenkel, Richard Krause, Dale Allison, John Browning, Steven Davis, Mark Lee, Kristina Duffin, Chester Tim Fisher, David Pariser, Richard G Gower, Stewart Adams, Mariusz Joseph Albert Sapijaszko, Norman Wasel, Lorne Albrecht, Chih-Ho Hong, Wayne Gulliver, Ian Landells, David Adam, Melinda Gooderham, Mark Lomaga, Charles Lynde, Leslie Rosoph, Mani Raman, Michael Robern, Sheetal Sapra, Darryl Toth, Yves Poulin, Martine Bagot, Sébastien Barbarot, Jean-Jacques Grob, Gérard Guillet, Jean-Philippe Lacour, Abdallah Khemis, Laurent Misery, Delphine Staumont-Sallé, Harald Brüning, Ulf Darsow, Swarna Ekanayake-Bohlig, Rudolf Herbst, Matthias Hoffmann, Bernhard Homey, Johannes Niesmann, Andreas Pinter, Peter Radny, Kristian Reich, Gerhard Sattler, Michael Sebastian, Diamant Thaçi, Stephan Weidinger, Thomas Wildfeuer, Margitta Worm, Henry Chan, Johnny Chan, Paolo Amerio, Marta Carlesimo, Vito Di Lernia, Reggio Emilia, Biagio Didona, Maria Fargnoli, Silvia Mariel Ferrucci, Luigi Naldi, Manuela Papini, Aurora Parodi, Giovanni Pellacani, Ketty Peris, Nicola Pimpinelli, Marco Romanelli, Marina Talamonti, Matilda Bylaite-Bucinskiene, Jolanta Cesiene, Redzinaldas Narbutas, Ruta Birute Sidlauskiene, Vesta Kucinskiene, Zygmunt Adamski, Dorota Bystrzanowska, Andrzej Dyczek, Teresa Hofman, Lucyna Leszniewska, Roman Nowicki, Witold Owczarek, Monika Slowinska, Anna Sobieszek-Kundro, Jolanta Weglowska, Marcin Zakrzewski, Hyo Hyun Ahn, Kyu Joong Ahn, Sung-Eun Chang, Gwang Seong Choi, Moon Bum Kim, Kyu Han Kim, Kwang Hoon Lee, Young Min Park, Chun Wook Park, Gyeong-Hun Park, Dong-Ho Nahm, Young Lip Park, Jooyoung Roh, Seong-Jun Seo, Mahreen Ameen, Michael Ardern-Jones, Anthony Bewley, Hywel Cooper, Michael J Cork, Binita Guha-Niyogi, Maqsood Khan, Marie Marshall, John Foerster, Catherine Smith, Melanie Appell, Boni Elewski, Stacy Haynes, S Sasha Jazayeri, Jeffrey Crowley, Sunil Dhawan, Mark Ellis, Suzanne Kim, Steven Meltzer, Jesse Mitchell, David Pearlman, Jeremy Moss, Alison Ehrlich, Seth Forman, Barry Kuttner, Felix Penate, Carlos Vaca, Tiffani Hamilton, William Paull, Jamie Weisman, Scott Glazer, Stephanie Mehlis, Scott Guenthner, Benjamin Lockshin, Alexa Kimball, David Rosmarin, Tina Pickett-Baisden, Philip Halverson, Harold Kaiser, Ann Martin, Melody Stone, Kathleen Davis, Vincent Mirkil, Robert Nossa, Elizabeth Bretton, Andrew Alexis, Emma Guttman-Yassky, Marina Peredo, Jeffrey Weinberg, Alan Fleischer, Rosalyn George, Aida Lugo-Somolinos, Adnan Nasir, Iftikhar Hussain, Andrew Blauvelt, Eric Simpson, Marvin Kalafer, Marta Hampton, John M Humeniuk, Ned Rupp, Daniel Carrasco, Brian MacGillivray, Angela Moore, Craig Teller, Stephen Tyring, Duane Harris, Peter Jenkin, Eric L Simpson, Thomas Bieber, Emma Guttman-Yassky, Lisa A Beck, Andrew Blauvelt, Michael J Cork, Jonathan I Silverberg, Mette Deleuran, Yoko Kataoka, Jean-Philippe Lacour, Külli Kingo, Margitta Worm, Yves Poulin, Andreas Wollenberg, Yuhwen Soo, Neil M H Graham, Gianluca Pirozzi, Bolanle Akinlade, Heribert Staudinger, Vera Mastey, Laurent Eckert, Abhijit Gadkari, Neil Stahl, George D Yancopoulos, Marius Ardeleanu, SOLO 1 and SOLO 2 Investigators, Elmira Nikolova-Pavlova, Boyka Stoyanova, Tzetza Vlaeva, Afsaneh Alavi, Gail Gauvreau, Sam Henein, Elena Poulos, William Yang, France Lepage, Marni Wiseman, Robert Bissonnette, Tove Agner, Mette Deleuran, Gregor Jemec, Lone Skov, Külli Kingo, Pille Konno, Kristi Pender, Airi Põder, Ave Vahlberg, Risto Oksman, Rafael Pasternack, Anita Remitz, Thomas Bieber, Rolf Dominicus, Beatrice Gerlach, Bernd Kardorff, Andreaa Laura Toader, Andreas Kleinheinz, Sylke Gellrich, Katharina Kreutzer, Nicolas Leitz, Michael Offers, Sylvia Pauser, Marc Radtke, Evelin Roloff, Thomas Rosenbach, Beate Schwarz, Sabine Sell, Jan-Christoph Simon, Petra Staubach, Ulrich Stefan Weigel, Thomas Werfel, Johannes Wohlrab, Andreas Wollenberg, Christoph Rothenberger, Alexandra Walter, Amir Yazdi, Michiko Aihara, Michihiro Hide, Yoko Kataoka, Norito Katoh, Makoto Kawashima, Satomi Kobayashi, Hiroshi Mitsui, Takeshin Nakahara, Hidehisa Saeki, Hirohiko Sueki, Satoru Arai, Masanori Ikeda, Kenji Kabashima, Yasuhiro Kawachi, Akihiro Kume, Shinichi Moriwaki, Yohei Natsuaki, Fuyuki Ogata, Tokuya Omi, Mariko Seishima, Makoto Sugaya, Katsuhiko Tsukamoto, Daisuke Tsuruta, Shoko Urano, Daisuke Watanabe, Akira Yoshioka, Fukumi Furukawa, Atsuko Katoh, Chia Chun Ang, Derrick Chen Wee Aw, Mark Tang, Haur Yueh Lee, Francesc Bordas Orpinell, Gregorio Carretero Hernández, Pablo De La Cueva, Carlos Ferrándiz Foraster, Pilar Iranzo, Anna Jucgla Serra, Pedro Lloret Luna, Servando Marrón Moya, David Moreno Ramírez, Javier Pedraz Muñoz, José Sánchez Carazo, Weily Soong, Cheryl Hull, Sandra Johnson, Neal Bhatia, Marketa Limova, Marina Raikhel, Lawrence Sher, Howard Sofen, Sheldon Spector, Ricardo Tan, Paul Yamauchi, Richard Weber, Stephen Kimura, Christopher Nelson, Shahid Randhawa, Marta Rendon, Miguel Trevino, Mark Ling, Zakiya Rice, Jonathan Silverberg, Dareen Siri, Scott Fretzin, Joseph F Fowler, Erin Boh, Joseph Merola, George Murakawa, Phillip Korenblat, James Campbell, Jerry Bagel, Lisa Beck, Carole Hazan, Robert Kalb, Christopher Smith, Jose Bardelas, Sandra Gawchik, Eric Schenkel, Richard Krause, Dale Allison, John Browning, Steven Davis, Mark Lee, Kristina Duffin, Chester Tim Fisher, David Pariser, Richard G Gower, Stewart Adams, Mariusz Joseph Albert Sapijaszko, Norman Wasel, Lorne Albrecht, Chih-Ho Hong, Wayne Gulliver, Ian Landells, David Adam, Melinda Gooderham, Mark Lomaga, Charles Lynde, Leslie Rosoph, Mani Raman, Michael Robern, Sheetal Sapra, Darryl Toth, Yves Poulin, Martine Bagot, Sébastien Barbarot, Jean-Jacques Grob, Gérard Guillet, Jean-Philippe Lacour, Abdallah Khemis, Laurent Misery, Delphine Staumont-Sallé, Harald Brüning, Ulf Darsow, Swarna Ekanayake-Bohlig, Rudolf Herbst, Matthias Hoffmann, Bernhard Homey, Johannes Niesmann, Andreas Pinter, Peter Radny, Kristian Reich, Gerhard Sattler, Michael Sebastian, Diamant Thaçi, Stephan Weidinger, Thomas Wildfeuer, Margitta Worm, Henry Chan, Johnny Chan, Paolo Amerio, Marta Carlesimo, Vito Di Lernia, Reggio Emilia, Biagio Didona, Maria Fargnoli, Silvia Mariel Ferrucci, Luigi Naldi, Manuela Papini, Aurora Parodi, Giovanni Pellacani, Ketty Peris, Nicola Pimpinelli, Marco Romanelli, Marina Talamonti, Matilda Bylaite-Bucinskiene, Jolanta Cesiene, Redzinaldas Narbutas, Ruta Birute Sidlauskiene, Vesta Kucinskiene, Zygmunt Adamski, Dorota Bystrzanowska, Andrzej Dyczek, Teresa Hofman, Lucyna Leszniewska, Roman Nowicki, Witold Owczarek, Monika Slowinska, Anna Sobieszek-Kundro, Jolanta Weglowska, Marcin Zakrzewski, Hyo Hyun Ahn, Kyu Joong Ahn, Sung-Eun Chang, Gwang Seong Choi, Moon Bum Kim, Kyu Han Kim, Kwang Hoon Lee, Young Min Park, Chun Wook Park, Gyeong-Hun Park, Dong-Ho Nahm, Young Lip Park, Jooyoung Roh, Seong-Jun Seo, Mahreen Ameen, Michael Ardern-Jones, Anthony Bewley, Hywel Cooper, Michael J Cork, Binita Guha-Niyogi, Maqsood Khan, Marie Marshall, John Foerster, Catherine Smith, Melanie Appell, Boni Elewski, Stacy Haynes, S Sasha Jazayeri, Jeffrey Crowley, Sunil Dhawan, Mark Ellis, Suzanne Kim, Steven Meltzer, Jesse Mitchell, David Pearlman, Jeremy Moss, Alison Ehrlich, Seth Forman, Barry Kuttner, Felix Penate, Carlos Vaca, Tiffani Hamilton, William Paull, Jamie Weisman, Scott Glazer, Stephanie Mehlis, Scott Guenthner, Benjamin Lockshin, Alexa Kimball, David Rosmarin, Tina Pickett-Baisden, Philip Halverson, Harold Kaiser, Ann Martin, Melody Stone, Kathleen Davis, Vincent Mirkil, Robert Nossa, Elizabeth Bretton, Andrew Alexis, Emma Guttman-Yassky, Marina Peredo, Jeffrey Weinberg, Alan Fleischer, Rosalyn George, Aida Lugo-Somolinos, Adnan Nasir, Iftikhar Hussain, Andrew Blauvelt, Eric Simpson, Marvin Kalafer, Marta Hampton, John M Humeniuk, Ned Rupp, Daniel Carrasco, Brian MacGillivray, Angela Moore, Craig Teller, Stephen Tyring, Duane Harris, Peter Jenkin
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 .).
Source: PubMed