Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma
Parameswaran Nair, Sally Wenzel, Klaus F Rabe, Arnaud Bourdin, Njira L Lugogo, Piotr Kuna, Peter Barker, Stephanie Sproule, Sandhia Ponnarambil, Mitchell Goldman, ZONDA Trial Investigators, Cristina De Salvo, Mariano Fernandez Acquier, Fernando Scherbovsky, Alberto Tolcachier, Dimitar Kostadinov, Hristo Metev, Kostadinka Sotirova, Mariyana Stoyanova, Oleg Yakov, Louis-Philippe Boulet, Delbert Dorscheid, James Martin, William Yang, Susana Munoz, Juana Pavie, Patricia Rivas, Gilles Devouassoux, Alain Didier, Christophe Leroyer, Regina Deckelmann, Joachim Kirschner, Stephanie Korn, Tobias Welte, Sang-Heon Cho, Byung-Jae Lee, Sang-Haak Lee, Sook Young Lee, Jung-Won Park, Renata Bijata-Bronisz, Andrzej Dyczek, Tomasz Fijolek, Grazyna Jasieniak-Pinis, Artur Kwasniewski, Ewa Pisarczyk-Bogacka, Malgorzata Zurowska-Gebala, Eva Martinez, José Luis Velasco, Sevim Bavbek, Dane Ediger, Bilun Gemicioglu, Ismail Hanta, Viktor Blazhko, Yevgenya Dytyatkovs’ka, Volodymyr Gavrysyuk, Olena Krakhmalova, Lesia Kuryk, Yuriy Mostovoy, Mykola Ostrovskyy, Liliia Romaniuk, David Bernstein, Eugene Bleecker, Gonzalo Gonzalez, Rohit Katial, Joel Kline, Mark Moss, John Panuto, Kartik Shenoy, Manuel Villareal, Parameswaran Nair, Sally Wenzel, Klaus F Rabe, Arnaud Bourdin, Njira L Lugogo, Piotr Kuna, Peter Barker, Stephanie Sproule, Sandhia Ponnarambil, Mitchell Goldman, ZONDA Trial Investigators, Cristina De Salvo, Mariano Fernandez Acquier, Fernando Scherbovsky, Alberto Tolcachier, Dimitar Kostadinov, Hristo Metev, Kostadinka Sotirova, Mariyana Stoyanova, Oleg Yakov, Louis-Philippe Boulet, Delbert Dorscheid, James Martin, William Yang, Susana Munoz, Juana Pavie, Patricia Rivas, Gilles Devouassoux, Alain Didier, Christophe Leroyer, Regina Deckelmann, Joachim Kirschner, Stephanie Korn, Tobias Welte, Sang-Heon Cho, Byung-Jae Lee, Sang-Haak Lee, Sook Young Lee, Jung-Won Park, Renata Bijata-Bronisz, Andrzej Dyczek, Tomasz Fijolek, Grazyna Jasieniak-Pinis, Artur Kwasniewski, Ewa Pisarczyk-Bogacka, Malgorzata Zurowska-Gebala, Eva Martinez, José Luis Velasco, Sevim Bavbek, Dane Ediger, Bilun Gemicioglu, Ismail Hanta, Viktor Blazhko, Yevgenya Dytyatkovs’ka, Volodymyr Gavrysyuk, Olena Krakhmalova, Lesia Kuryk, Yuriy Mostovoy, Mykola Ostrovskyy, Liliia Romaniuk, David Bernstein, Eugene Bleecker, Gonzalo Gonzalez, Rohit Katial, Joel Kline, Mark Moss, John Panuto, Kartik Shenoy, Manuel Villareal
Abstract
Background: Many patients with severe asthma rely on oral glucocorticoids to manage their disease. We investigated whether benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor that significantly reduces the incidence of asthma exacerbations, was also effective as an oral glucocorticoid-sparing therapy in patients relying on oral glucocorticoids to manage severe asthma associated with eosinophilia.
Methods: In a 28-week randomized, controlled trial, we assessed the effects of benralizumab (at a dose of 30 mg administered subcutaneously either every 4 weeks or every 8 weeks [with the first three doses administered every 4 weeks]) versus placebo on the reduction in the oral glucocorticoid dose while asthma control was maintained in adult patients with severe asthma. The primary end point was the percentage change in the oral glucocorticoid dose from baseline to week 28. Annual asthma exacerbation rates, lung function, symptoms, and safety were assessed.
Results: Of 369 patients enrolled, 220 underwent randomization and started receiving benralizumab or placebo. The two benralizumab dosing regimens significantly reduced the median final oral glucocorticoid doses from baseline by 75%, as compared with a reduction of 25% in the oral glucocorticoid doses in the placebo group (P<0.001 for both comparisons). The odds of a reduction in the oral glucocorticoid dose were more than 4 times as high with benralizumab as with placebo. Among the secondary outcomes, benralizumab administered every 4 weeks resulted in an annual exacerbation rate that was 55% lower than the rate with placebo (marginal rate, 0.83 vs. 1.83, P=0.003), and benralizumab administered every 8 weeks resulted in an annual exacerbation rate that was 70% lower than the rate with placebo (marginal rate, 0.54 vs. 1.83, P<0.001). At 28 weeks, there was no significant effect of either benralizumab regimen on the forced expiratory volume in 1 second (FEV1), as compared with placebo. The effects on various measures of asthma symptoms were mixed, with some showing significant changes in favor of benralizumab and others not showing significant changes. Frequencies of adverse events were similar between each benralizumab group and the placebo group.
Conclusions: Benralizumab showed significant, clinically relevant benefits, as compared with placebo, on oral glucocorticoid use and exacerbation rates. These effects occurred without a sustained effect on the FEV1. (Funded by AstraZeneca; ZONDA ClinicalTrials.gov number, NCT02075255 .).
Source: PubMed