Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies.

Autor:	Hanania NA; Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, Texas, USA., Noonan M; Allergy Associates Research, Portland, Oregon, USA., Corren J; Asthma and Allergy Research Foundation, Los Angeles, California, USA., Korenblat P; Clinical Research Center LLC, St. Louis, Missouri, USA., Zheng Y; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., Fischer SK; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., Cheu M; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., Putnam WS; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., Murray E; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., Scheerens H; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., Holweg CT; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., Maciuca R; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., Gray S; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., Doyle R; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., McClintock D; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., Olsson J; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., Matthews JG; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA., Yen K; Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
Jazyk:	angličtina
Zdroj:	Thorax [Thorax] 2015 Aug; Vol. 70 (8), pp. 748-56. Date of Electronic Publication: 2015 May 22.
DOI:	10.1136/thoraxjnl-2014-206719
Abstrakt:	Introduction: In a subset of patients with asthma, standard-of-care treatment does not achieve disease control, highlighting the need for novel therapeutic approaches. Lebrikizumab is a humanised, monoclonal antibody that binds to and blocks interleukin-13 activity. Methods: LUTE and VERSE were replicate, randomised, double-blind, placebo-controlled studies, evaluating multiple doses of lebrikizumab in patients with uncontrolled asthma despite the use of medium-to-high-dose inhaled corticosteroid and a second controller. Patients received lebrikizumab 37.5, 125, 250 mg or placebo subcutaneously every four weeks. The primary endpoint was the rate of asthma exacerbations during the placebo-controlled period. Analyses were performed on prespecified subgroups based on baseline serum periostin levels. Following the discovery of a host-cell impurity in the study drug material, protocols were amended to convert from phase III to phase IIb. Subsequently, dosing of study medication was discontinued early as a precautionary measure. The data collected for analysis were from a placebo-controlled period of variable duration and pooled across both studies. Results: The median duration of treatment was approximately 24 weeks. Treatment with lebrikizumab reduced the rate of asthma exacerbations, which was more pronounced in the periostin-high patients (all doses: 60% reduction) than in the periostin-low patients (all doses: 5% reduction); no dose-response was evident. Lung function also improved following lebrikizumab treatment, with greatest increase in FEV1 in periostin-high patients (all doses: 9.1% placebo-adjusted improvement) compared with periostin-low patients (all doses: 2.6% placebo-adjusted improvement). Lebrikizumab was well tolerated and no clinically important safety signals were observed. Conclusions: These data are consistent with, and extend, previously published results demonstrating the efficacy of lebrikizumab in improving rate of asthma exacerbations and lung function in patients with moderate-to-severe asthma who remain uncontrolled despite current standard-of-care treatment. Trial Registration Numbers: The LUTE study was registered under NCT01545440 and the VERSE study under NCT01545453 at http://www.clinicaltrials.gov. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
Databáze:	MEDLINE
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