Effect of omalizumab on peripheral blood eosinophilia in allergic asthma

Abstract

Eosinophilia is an established marker of asthma-related inflammation. We assessed the effect of omalizumab on peripheral blood eosinophil counts using a pooled analysis of data from five randomized, double-blind, placebo-controlled studies in patients with moderate-to-severe persistent allergic asthma receiving moderate-to-high-dose inhaled corticosteroids (omalizumab, n=1136; placebo, n=1100). Relationships between omalizumab, peripheral blood eosinophils, serum free IgE concentrations and clinical outcomes were explored. Baseline mean eosinophil counts were similar in each treatment group. Post-treatment eosinophil counts were significantly reduced from baseline in the omalizumab group (p<0.0001) but were not significantly different in the placebo group. Greater reductions in eosinophil counts were observed in patients who had post-treatment free IgE levels <50ng/mL. Three studies included steroid-stable and steroid-reduction phases. At the end of each phase in these studies, a significantly greater reduction in eosinophil counts was achieved in the omalizumab group compared with the placebo group (p<0.0001). A consistent pattern of improved clinical outcomes/decreased eosinophils and worsened clinical outcomes/increased eosinophils was observed for both omalizumab and placebo treatment groups. The findings from our analysis of a large patient population are consistent with earlier reports of the inhibitory effect of omalizumab on eosinophils.

Improving the diagnosis of eosinophilic asthma

“…Thus, of all currently available biomarkers to detect eosinophilic asthma, IgE seems to be the least useful. This does however not exclude that IgE can be used to identify patients who will likely benefit form anti-IgE therapy, nor that anti-IgE can have a beneficial effect in subgroups of patients with eosinophilic asthma [51].…”

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

“…In Massanari's pooled analysis of five clinical trials [53] on the efficacy of omalizumab in patients with persistent moderate/severe allergic asthma, the post-treatment number of peripheral eosinophils compared to baseline was reduced only in the group of patients receiving omalizumab, with a greater reduction in eosinophil count observed in those in whom the serum free IgE levels were lower than 50 ng/ml. The researchers also found a correlation between the omalizumab-induced decrease in peripheral eosinophils and various clinical parameters, including the occurrence of severe exacerbations, FEV1 value, a response to omalizumab treatment assessed by physicians on GETE (the Global Evaluation of Treatment Effectiveness) scale (correlation between clinical improvement and reduction in the number of eosinophils and between no improvement and increase in the number of eosinophils).…”

“…NO inhibits apoptosis dependent on the activation of the Fas receptor [93]. Increased levels of NO are observed in asthma, while omalizumab therapy significantly reduces the NO concentration in the exhaled air [28,34,53,55,56], which may be important for regression of eosinophilic inflammation in the airways.…”

Severe Asthma: Anti-IgE or Anti-IL-5?

“…Mepolizumab almost depletes eosinophils from peripheral blood and significantly reduces them from the airways, and omalizumab also reduces sputum and tissue eosinophils, as it has been shown in lung biopsy studies (14,58). In a pooled analysis from five randomised, double-blind, placebocontrolled studies including patients with moderateto-severe persistent allergic asthma, omalizumab was associated with significantly reduced post-treatment peripheral blood eosinophil counts (13). Moreover, the greater reductions were observed in those patients with lower post-treatment free IgE levels.…”