Mepolizumab treatment in patients with severe eosinophilic asthma
Hector G Ortega, Mark C Liu, Ian D Pavord, Guy G Brusselle, J Mark FitzGerald, Alfredo Chetta, Marc Humbert, Lynn E Katz, Oliver N Keene, Steven W Yancey, Pascal Chanez, MENSA Investigators, Ledit Ardusso, María De Salvo, Ernesto Raso, Luisa Rey, Alicia Rodriguez, Pablo Saez Scherbovsky, Luis Wehbe, Philip Bardin, Peter Gibson, Philip Robinson, Dimitar Sajkov, Philip Thompson, Guy Brusselle, Lieven Dupont, Renaud Louis, Olivier Michel, Celine Bergeron, Mohit Bhutani, J Mark FitzGerald, Pierre-Alain Houle, Kieran Killian, Patrick Killorn, Michel Laviolette, Richard Leigh, Catherine Lemiere, James Martin, Bonavuth Pek, Satyendra Sharma, Carlos Bisbal, Malig Patricio, Rioseco Saavedra, Rafael Silva Orellana, Sergio Vargas, Arnaud Bourdin, Pascal Chanez, Antoine Deschildre, Gilles Devouassoux, Marc Humbert, Fabrice Paganin, Serge Verdier, Benoît Wallaert, Sabine Ballenberger, Ekkehard Beck, Martin Ehlers, Karin Foerster, Siegrid Hofmann, Gabriele Illies, Claus Keller, Stephanie Korn, Oliver Kornmann, Mathias Rolke, Winfried Schroeder-Babo, Stefan Zielen, Stefano Baglioni, Giorgio Walter Canonica, Alfredo Chetta, Mariapia Foschino Barbaro, Giuseppe Idotta, Carlo Mereu, PierLuigi Paggiaro, Matteo Sofia, Stanziola Anna Agnese, Yasushi Fukushima, Michiko Haida, Toshiyuki Harada, Osamu Hataji, Soichiro Hozawa, Norihiro Kaneko, Motokazu Kato, Kiyokazu Kikuchi, Masaharu Kinoshita, Tomoo Kishaba, Mitsuhiro Matsumoto, Hirofumi Matsuoka, Masahide Mori, Yuji Nakatani, Hiroshi Odajima, Kazuhiko Oki, Takefumi Saito, Hisakuni Ekino, Terufumi Shimoda, Kazuyo Tohyama, Takahiro Tsuburai, Tohru Tsuda, Yasuhiro Yamazaki, Byoung Whui Choi, Ki-Suck Jung, Mi-Kyeong Kim, Young-Il Koh, Yong Chul Lee, Sang Pyo Lee, Kwan-Ho Lee, Choon-Sik Park, Hae-Sim Park, Jung-Won Park, Suk-joong Yong, Jesús-Javier Díaz-Castañon, José Angel Garza-Ruiz, Alfredo Gazca-Aguilar, Alejandra Ramirez-Venegas, Ludmila Goryachkina, Galina Ignatova, Yulia Ilkovich, Natalia Shaporova, Carolina Cisneros Serrano, Luis De Teresa Parreño, Christian Domingo Ribas, José Maria Echave-Sustaeta, Cesar Picado Valles, David Ramos Barbon, Viktor Blazhko, Yuriy Feshchenko, Liudmyla Iashyna, Valeriy Molodtsov, Mykola Stanislavchuk, Neil Barnes, Peter Howarth, Matthew Masoli, Dinesh Saralaya, Malcolm Shepherd, Amal Assa'ad, David Bernstein, Eugene Bleecker, Tracy Bridges, Geoffrey Chupp, Timothy Craig, Mark Dransfield, John Fahrenholz 2nd, Gerald Gleich, John Hagan, Rohit Katial, Sumita Khatri, Sandhya Khurana, Ryan Klein, Mark Liu, Njira Lugogo, Amit Patel, Lawrence Sher, Gwen Skloot, Hector G Ortega, Mark C Liu, Ian D Pavord, Guy G Brusselle, J Mark FitzGerald, Alfredo Chetta, Marc Humbert, Lynn E Katz, Oliver N Keene, Steven W Yancey, Pascal Chanez, MENSA Investigators, Ledit Ardusso, María De Salvo, Ernesto Raso, Luisa Rey, Alicia Rodriguez, Pablo Saez Scherbovsky, Luis Wehbe, Philip Bardin, Peter Gibson, Philip Robinson, Dimitar Sajkov, Philip Thompson, Guy Brusselle, Lieven Dupont, Renaud Louis, Olivier Michel, Celine Bergeron, Mohit Bhutani, J Mark FitzGerald, Pierre-Alain Houle, Kieran Killian, Patrick Killorn, Michel Laviolette, Richard Leigh, Catherine Lemiere, James Martin, Bonavuth Pek, Satyendra Sharma, Carlos Bisbal, Malig Patricio, Rioseco Saavedra, Rafael Silva Orellana, Sergio Vargas, Arnaud Bourdin, Pascal Chanez, Antoine Deschildre, Gilles Devouassoux, Marc Humbert, Fabrice Paganin, Serge Verdier, Benoît Wallaert, Sabine Ballenberger, Ekkehard Beck, Martin Ehlers, Karin Foerster, Siegrid Hofmann, Gabriele Illies, Claus Keller, Stephanie Korn, Oliver Kornmann, Mathias Rolke, Winfried Schroeder-Babo, Stefan Zielen, Stefano Baglioni, Giorgio Walter Canonica, Alfredo Chetta, Mariapia Foschino Barbaro, Giuseppe Idotta, Carlo Mereu, PierLuigi Paggiaro, Matteo Sofia, Stanziola Anna Agnese, Yasushi Fukushima, Michiko Haida, Toshiyuki Harada, Osamu Hataji, Soichiro Hozawa, Norihiro Kaneko, Motokazu Kato, Kiyokazu Kikuchi, Masaharu Kinoshita, Tomoo Kishaba, Mitsuhiro Matsumoto, Hirofumi Matsuoka, Masahide Mori, Yuji Nakatani, Hiroshi Odajima, Kazuhiko Oki, Takefumi Saito, Hisakuni Ekino, Terufumi Shimoda, Kazuyo Tohyama, Takahiro Tsuburai, Tohru Tsuda, Yasuhiro Yamazaki, Byoung Whui Choi, Ki-Suck Jung, Mi-Kyeong Kim, Young-Il Koh, Yong Chul Lee, Sang Pyo Lee, Kwan-Ho Lee, Choon-Sik Park, Hae-Sim Park, Jung-Won Park, Suk-joong Yong, Jesús-Javier Díaz-Castañon, José Angel Garza-Ruiz, Alfredo Gazca-Aguilar, Alejandra Ramirez-Venegas, Ludmila Goryachkina, Galina Ignatova, Yulia Ilkovich, Natalia Shaporova, Carolina Cisneros Serrano, Luis De Teresa Parreño, Christian Domingo Ribas, José Maria Echave-Sustaeta, Cesar Picado Valles, David Ramos Barbon, Viktor Blazhko, Yuriy Feshchenko, Liudmyla Iashyna, Valeriy Molodtsov, Mykola Stanislavchuk, Neil Barnes, Peter Howarth, Matthew Masoli, Dinesh Saralaya, Malcolm Shepherd, Amal Assa'ad, David Bernstein, Eugene Bleecker, Tracy Bridges, Geoffrey Chupp, Timothy Craig, Mark Dransfield, John Fahrenholz 2nd, Gerald Gleich, John Hagan, Rohit Katial, Sumita Khatri, Sandhya Khurana, Ryan Klein, Mark Liu, Njira Lugogo, Amit Patel, Lawrence Sher, Gwen Skloot
Abstract
Background: Some patients with severe asthma have frequent exacerbations associated with persistent eosinophilic inflammation despite continuous treatment with high-dose inhaled glucocorticoids with or without oral glucocorticoids.
Methods: In this randomized, double-blind, double-dummy study, we assigned 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled glucocorticoids to one of three study groups. Patients were assigned to receive mepolizumab, a humanized monoclonal antibody against interleukin-5, which was administered as either a 75-mg intravenous dose or a 100-mg subcutaneous dose, or placebo every 4 weeks for 32 weeks. The primary outcome was the rate of exacerbations. Other outcomes included the forced expiratory volume in 1 second (FEV1) and scores on the St. George's Respiratory Questionnaire (SGRQ) and the 5-item Asthma Control Questionnaire (ACQ-5). Safety was also assessed.
Results: The rate of exacerbations was reduced by 47% (95% confidence interval [CI], 29 to 61) among patients receiving intravenous mepolizumab and by 53% (95% CI, 37 to 65) among those receiving subcutaneous mepolizumab, as compared with those receiving placebo (P<0.001 for both comparisons). Exacerbations necessitating an emergency department visit or hospitalization were reduced by 32% in the group receiving intravenous mepolizumab and by 61% in the group receiving subcutaneous mepolizumab. At week 32, the mean increase from baseline in FEV1 was 100 ml greater in patients receiving intravenous mepolizumab than in those receiving placebo (P=0.02) and 98 ml greater in patients receiving subcutaneous mepolizumab than in those receiving placebo (P=0.03). The improvement from baseline in the SGRQ score was 6.4 points and 7.0 points greater in the intravenous and subcutaneous mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 4 points), and the improvement in the ACQ-5 score was 0.42 points and 0.44 points greater in the two mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 0.5 points) (P<0.001 for all comparisons). The safety profile of mepolizumab was similar to that of placebo.
Conclusions: Mepolizumab administered either intravenously or subcutaneously significantly reduced asthma exacerbations and was associated with improvements in markers of asthma control. (Funded by GlaxoSmithKline; MENSA ClinicalTrials.gov number, NCT01691521.).
Source: PubMed