We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
A randomized trial of the efficacy and safety of quilizumab in adults with inadequately controlled allergic asthma.
- Authors
Harris, Jeffrey M.; Maciuca, Romeo; Bradley, Mary S.; Cabanski, Christopher R.; Scheerens, Heleen; Jeremy Lim; Cai, Fang; Kishnani, Mona; Liao, X. Charlene; Samineni, Divya; Zhu, Rui; Cochran, Colette; Soong, Weily; Diaz, Joseph D.; Perin, Patrick; Tsukayama, Miguel; Dimov, Dimo; Agache, Ioana; Kelsen, Steven G.; Lim, Jeremy
- Abstract
<bold>Background: </bold>Quilizumab, a humanized IgG1 monoclonal antibody, targets the M1-prime segment of membrane-expressed IgE, leading to depletion of IgE-switched and memory B cells. In patients with mild asthma, quilizumab reduced serum IgE and attenuated the early and late asthmatic reaction following whole lung allergen challenge. This study evaluated the efficacy and safety of quilizumab in adults with allergic asthma, inadequately controlled despite high-dose inhaled corticosteroids (ICS) and a second controller.<bold>Methods: </bold>Five hundred seventy-eight patients were randomized to monthly or quarterly dosing regimens of subcutaneous quilizumab or placebo for 36 weeks, with a 48-week safety follow-up. Quilizumab was evaluated for effects on the rate of asthma exacerbations, lung function, patient symptoms, serum IgE, and pharmacokinetics. Exploratory analyses were conducted on biomarker subgroups (periostin, blood eosinophils, serum IgE, and exhaled nitric oxide).<bold>Results: </bold>Quilizumab was well tolerated and reduced serum total and allergen-specific IgE by 30-40 %, but had no impact on asthma exacerbations, lung function, or patient-reported symptom measures. At Week 36, the 300 mg monthly quilizumab group showed a 19.6 % reduction (p = 0.38) in the asthma exacerbation rate relative to placebo, but this was neither statistically nor clinically significant. Biomarker subgroups did not reveal meaningful efficacy benefits following quilizumab treatment.<bold>Conclusions: </bold>Quilizumab had an acceptable safety profile and reduced serum IgE. However, targeting the IgE pathway via depletion of IgE-switched and memory B cells was not sufficient for a clinically meaningful benefit for adults with allergic asthma uncontrolled by standard therapy.<bold>Trial Registration: </bold>ClinicalTrials.gov NCT01582503.
- Subjects
ASTHMA treatment; IMMUNOGLOBULIN E; MONOCLONAL antibodies; ALLERGY treatment; ANTIASTHMATIC agents; THERAPEUTICS; ASTHMA diagnosis; DRUG therapy for asthma; DISEASE relapse prevention; ADRENOCORTICAL hormones; ALLERGIES; ASTHMA; BRONCHODILATOR agents; COMBINED modality therapy; COMPARATIVE studies; DOSE-effect relationship in pharmacology; IMMUNOGLOBULINS; RESEARCH methodology; MEDICAL cooperation; RESEARCH; EVALUATION research; RANDOMIZED controlled trials; TREATMENT effectiveness; INHALATION administration; DIAGNOSIS
- Publication
Respiratory Research, 2016, Vol 17, p1
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/s12931-016-0347-2