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A sthma is a prevalent and heterogeneous disease that not only has a marked effect on the quality of life of affected patients but also imparts a signifi cant economic burden on society. The term "refractory asthma" (RA) is used for patients with persistent asthma symptoms in whom comorbidities have been treated, triggers addressed, compliance with treatment evaluated, and alternative diagnoses excluded. 1 The link between bacterial processes and RA has emerged as various phenotypes of chronic asthma with persistent infl ammation have been recognized. [2][3][4][5][6][7] Many studies have implicated Mycoplasma pneumoniae (Mp) in the initiation and persistence of asthma, although the precise role it plays and its pathogenic mechanisms remain elusive. 8 However, several limitations exist in studies of Mp in asthma, including the inability to consistently culture this organism, the poor performance of Mp serology in defi ning active infection, and the variable sensitivities of polymerase chain reaction (PCR) assays in detecting Mp.Recently, our group identifi ed a 68-kDa protein unique to Mp called the community-acquired respiratory distress syndrome toxin (CARDS Tx). CARDS Tx is a highly immunogenic protein that possesses Abbreviations: CARDS Tx 5 community-acquired respiratory distress syndrome toxin; ELISA 5 enzyme-linked immunosorbent assay; Mp 5 Mycoplasma pneumoniae ; P1 5 P1 adhesin; PCR 5 polymerase chain reaction; RA 5 refractory asthma; rCARDS Tx 5 recombinant community-acquired respiratory distress syndrome toxin; rP1 5 recombinant P1 adhesin immunodominant carboxy domain

BackgroundQuilizumab, 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.MethodsFive 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).ResultsQuilizumab 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.ConclusionsQuilizumab 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.Trial registrationClinicalTrials.gov NCT01582503Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0347-2) contains supplementary material, which is available to authorized users.