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Reslizumab for Inadequately Controlled Asthma With Elevated Blood Eosinophil Levels : A Randomized Phase 3 Study
Leif Bjermer MD, Catherine Lemiere MD, Jorge Maspero MD, Sivan Weiss MSc, James Zangrilli MD, Matthew Germinaro MD
Asthma is a very heterogeneous chronic disease, with many patients expressing persistent symptomsdespite treatment. Efforts have been made to characterize this treatment-resistant group fromothers thereby identifying a population characterized by eosinophilic airway inflammation.Eosinophils are dependant on the cytokine interleukin 5 (IL-5) for differentiation, activation andsurvival. Targeting IL-5 by the humanized monoclonal antibody reslizumab have shown in previousstudies to improve lung function and to achieve a greater asthma control.
The efficacy and safety of reslizumab in patients with persistent asthma inadequately controlled byinhaled corticosteroids and a blood eosinophil count ≥ 400 cells/µL were assessed in randomized,double-blind, placebo-controlled, parallel-group phase III trial as part of the BREATH program.Patients (12-75 years) received infusions of reslizumab 0.3 mg/kg, reslizumab 3.0 mg/kg, or placeboonce every 4 weeks (total 4 doses). Efficacy variables include FEV1, FVC, Asthma ControlQuestionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ), rescue inhaler use, bloodeosinophil counts and safety.
This phase III study showed that reslizumab 0.3 mg/kg and 3.0 mg/kg significantly improved FEV1compared with placebo. Greater improvement was achieved with reslizumab 3.0 mg/kg. Substantialincreases in FVC were observed with reslizumab 3.0 mg/kg suggesting that patients may need higherdoses to improve this parameter. Reslizumab (0.3 and 3.0 mg/kg) improved ACQ and decreasedblood eosinophil count with reslizumab 3.0 mg/kg being superior to reslizumab 0.3 mg/kg.Reslizumab (0.3 and 3.0 mg/kg) improved rescue inhaler use and reslizumab 3.0 mg/kg AQLQ scores.Treatment related adverse effects were mild to moderate in severity, the most frequent beingheadache, worsening of asthma, nasopharyngitis, and upper respiratory tract infection. Safety wassimilar in reslizumab 0.3 mg/kg and 3.0 mg/kg, demonstrating that the higher benefit of reslizumab3.0 mg/kg is not linked to decreased safety.
Reslizumab was effective at improving lung function, asthma control, and quality of life compared toplacebo in patients with persistent asthma and elevated blood eosinophils who are inadequatelycontrolled by standard asthma therapies. The clinical benefit of reslizumab 3.0 mg/kg was greaterthan that provided with reslizumab 0.3 mg/kg.