A Proof-of-Concept, Randomized, Controlled Trial of Omalizumab in Patients With Severe, Difficult-to-Control, Nonatopic Asthma

doi:10.1378/chest.12-1961

Chest

Volume 144, Issue 2, August 2013, Pages 411-419

https://doi.org/10.1378/chest.12-1961 Get rights and content

Background

While up to 50% of patients with severe asthma have no evidence of allergy, IgE has been linked to asthma, irrespective of atopic status. Omalizumab, an anti-IgE monoclonal antibody, is reported to significantly benefit a subset of patients with severe, persistent, allergic asthma. Therefore, we investigated whether omalizumab has biologic and clinical effects in patients with refractory nonatopic asthma.

Methods

Forty-one adult patients who, despite daily treatment with or without maintenance oral corticosteroids, had severe, nonatopic, refractory asthma according to GINA (Global Initiative for Asthma) step 4, were randomized to receive omalizumab or placebo in a 1:1 ratio. The primary end point was the change in expression of high-affinity IgE receptor (FcεRI) on blood basophils and plasmacytoid dendritic cells (pDC2) after 16 weeks. The impact of omalizumab on lung function and clinical variables was also examined.

Results

Compared with placebo, omalizumab resulted in a statistically significant reduction in FcεRI expression on basophils and pDC2 (P < .001). The omalizumab group also showed an overall increase in FEV₁ compared with baseline (+250 mL, P = .032; +9.9%, P = .029). A trend toward improvement in global evaluation of treatment effectiveness and asthma exacerbation rate was also observed.

Conclusions

Omalizumab negatively regulates FcεRI expression in patients with severe nonatopic asthma, as it does in severe atopic asthma. Omalizumab may have a therapeutic role in severe nonatopic asthma. Nonetheless, our preliminary findings support further investigation to better assess the clinical efficacy of omalizumab.

Trial registry

ClinicalTrials.gov; No.: NCT01007149; URL: www.clinicaltrials.gov and European Clinical Trials Database, EudraCT; No.: 2009-010937-38; URL: https://www.clinicaltrialsregister.eu

Section snippets

Materials and Methods

The study was conducted according to the Declaration of Helsinki principles and approved by the Ile de France XI ethics committee. All participants gave written informed consent.

Demographic and Baseline Characteristics

Of the 79 patients who underwent screening, 41 were enrolled in the study (omalizumab, n = 20; placebo, n = 21) (Figure 1, Table 1). The high rate of screening failures (48%) was mainly due to the finding of atopy at screening, serum total IgE level < 30 IU/mL (14 patients), or both. The mean total IgE was 157 IU/mL. All patients were treated with high doses of ICS in association with LABA, and 36.6% (n = 15) also were taking oral corticosteroids. In the year preceding the study, the mean (SD)

Discussion

The main findings of this study are as follows. First, omalizumab reduced FcεRI expression on basophils and pDC2s in a very well-characterized population of patients with severe, nonatopic asthma. Second, omalizumab was associated with clinical and statistical improvement in FEV₁ and with a positive trend in some relevant clinical end points, such as asthma exacerbations.

So-called intrinsic asthma was initially described as a clinical variant of asthma not triggered by environmental exposures.¹

Acknowledgments

Author contributions: Dr Humbert had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Garcia: contributed to study concept, design, and conduct; data collection, analysis, and interpretation; writing and revising the manuscript; and approval of the final manuscript; and served as principal author.

Dr Magnan: contributed to data collection, analysis, and interpretation; and writing and revising the

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Funding/Support: This study was supported by Novartis Pharma SAS.

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Chest

Original ResearchAsthmaA Proof-of-Concept, Randomized, Controlled Trial of Omalizumab in Patients With Severe, Difficult-to-Control, Nonatopic Asthma

Background

Methods

Results

Conclusions

Trial registry

Section snippets

Materials and Methods

Demographic and Baseline Characteristics

Discussion

Acknowledgments

Am J Med

Immunol Today

Respir Med

J Allergy Clin Immunol

J Allergy Clin Immunol

Respir Med

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Chest

Chest

Allergic vs nonallergic asthma: what makes the difference?

Allergy

Global strategy for asthma management and prevention: GINA executive summary

Eur Respir J

Original Research
Asthma
A Proof-of-Concept, Randomized, Controlled Trial of Omalizumab in Patients With Severe, Difficult-to-Control, Nonatopic Asthma