Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies.
Thorax
; 70(8): 748-56, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-26001563
ABSTRACT
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, 250â mg or placebo subcutaneously every fourâ 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 24â 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
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Pulmão
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Anticorpos Monoclonais
Tipo de estudo:
Diagnostic_studies
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Guideline
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Observational_studies
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Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article