Omalizumab in patients with severe asthma and persistent sputum eosinophilia

Abstract

Omalizumab, a recombinant humanized monoclonal antibody targeting the IgE molecule, is the first biologic approved for moderate-to-severe allergic asthmatics, who remain uncontrolled despite high dose inhaled corticosteroid and bronchodilators. Steroid-sparing effect of omalizumab has not been demonstrated in asthmatics with persistent airway eosinophilia in a randomised controlled trial till date. From this double-blind, placebo-controlled, multi-centred, randomized parallel group design, we report that omalizumab is possibly inadequate to control sputum eosinophilia, and therefore may not have a steroid-sparing effect, especially in those maintained on oral corticosteroids daily. This needs to be confirmed or refuted in a larger trial, which may be a challenge with respect to recruitment, since there are currently three additional biologics available to prescribe. Trial registration Clinicaltrials.gov, NCT02049294, Registered 30th January 2014, https://ichgcp.net/clinical-trials-registry/NCT02049294.

Keywords: IgE; Omalizumab; Severe asthma; Sputum eosinophils; TSLP.

Conflict of interest statement

PN reports grants from AZ, Novartis (current submitted manuscript), Teva, Sanofi. He has received consultant fees from Roche, Teva, Novartis, Knopp, outside the submitted work. MM no conflicts of interest to declare. CL reports grants from AZ and TEVA Innovation. She has received consultant fees from AZ, GSK, Sanofi Genzyme, Teva Innovation, outside the submitted work. RL has received grant funding from AstraZeneca, MedImmune, Novartis and Sanofi (outside the submitted work and paid to his institution) and honoraria and speaker’s fees from AstraZeneca, the Canadian Thoracic Society and Teva Canada. SW has received grant funding from MedImmune, and honoraria from Novartis Astra Zeneca, and Teva Canada. MM, MK, KR, CH has nothing to declare.

Figures

Fig. 1

Consort flow diagram of patient recruitment: details of patient recruitment process, study and analysis is provided in a schematic

Fig. 2

Effect of omalizumab on eosinophilia and indices of asthma severity: no significant reduction in eosinophils in the a sputum or b circulation, nor in the measurements of c fractional exhaled nitric oxide (FeNO), d asthma control (ACQ-5), or e FEV1 %predicted, could be documented for patients in the drug arm compared to placebo. Bars within the plots indicate the mean value for each group, and the delta (∆) values reflecting the mean absolute change within the group is give. Changes from baseline were compared for each arm using Wilcoxon paired analysis. P values were > 0.05, and were deemed non-significant