[HTML][HTML] Lebrikizumab treatment in adults with asthma

J Corren, RF Lemanske Jr, NA Hanania… - … England Journal of …, 2011 - Mass Medical Soc
J Corren, RF Lemanske Jr, NA Hanania, PE Korenblat, MV Parsey, JR Arron, JM Harris
New England Journal of Medicine, 2011Mass Medical Soc
Background Many patients with asthma have uncontrolled disease despite treatment with
inhaled glucocorticoids. One potential cause of the variability in response to treatment is
heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype. We
hypothesized that anti–interleukin-13 therapy would benefit patients with asthma who had a
pretreatment profile consistent with interleukin-13 activity. Methods We conducted a
randomized, double-blind, placebo-controlled study of lebrikizumab, a monoclonal antibody …
Background
Many patients with asthma have uncontrolled disease despite treatment with inhaled glucocorticoids. One potential cause of the variability in response to treatment is heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype. We hypothesized that anti–interleukin-13 therapy would benefit patients with asthma who had a pretreatment profile consistent with interleukin-13 activity.
Methods
We conducted a randomized, double-blind, placebo-controlled study of lebrikizumab, a monoclonal antibody to interleukin-13, in 219 adults who had asthma that was inadequately controlled despite inhaled glucocorticoid therapy. The primary efficacy outcome was the relative change in prebronchodilator forced expiratory volume in 1 second (FEV1) from baseline to week 12. Among the secondary outcomes was the rate of asthma exacerbations through 24 weeks. Patient subgroups were prespecified according to baseline type 2 helper T-cell (Th2) status (assessed on the basis of total IgE level and blood eosinophil count) and serum periostin level.
Results
At baseline, patients had a mean FEV1 that was 65% of the predicted value and were taking a mean dose of inhaled glucocorticoids of 580 μg per day; 80% were also taking a long-acting beta-agonist. At week 12, the mean increase in FEV1 was 5.5 percentage points higher in the lebrikizumab group than in the placebo group (P=0.02). Among patients in the high-periostin subgroup, the increase from baseline FEV1 was 8.2 percentage points higher in the lebrikizumab group than in the placebo group (P=0.03). Among patients in the low-periostin subgroup, the increase from baseline FEV1 was 1.6 percentage points higher in the lebrikizumab group than in the placebo group (P=0.61). Musculoskeletal side effects were more common with lebrikizumab than with placebo (13.2% vs. 5.4%, P=0.045).
Conclusions
Lebrikizumab treatment was associated with improved lung function. Patients with high pretreatment levels of serum periostin had greater improvement in lung function with lebrikizumab than did patients with low periostin levels. (Funded by Genentech; ClinicalTrials.gov number, NCT00930163.)
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