Omalizumab Asthma Trials Analyzed to Identify Best Responders

An analysis of the 2 trials that were pivotal to the approval of omalizumab (Xolair) for treatment of asthma has identified characteristics of patients most likely to respond.

Thomas Casale (pictured), MD — Division of Allergy and Immunology, University of South Florida, Tampa, Florida — and colleagues point out that the heterogeneous nature of asthma makes it particularly important to identify predictors of treatment response, to facilitate more precise approaches to treatment.

The investigators cite studies which suggest that clinical and biologic markers of asthma severity predict the level of response to biologic treatments of asthma. Although they did not find that populations in the phase 3 trials for omalizumab were enriched for these factors, they identified cohorts in studies with other biologic therapies that would enable better characterization of potential responders.

To examine factors associated with response to omalizumab, the investigators applied a patient enrichment post-hoc analysis to the 2 phase 3 studies that supported FDA approval of the agent. The analysis of the studies simulated a greater number of subjects with characteristics likely to predict response, drawn from data of the cohort with reduced asthma exacerbations in the DREAM studies with mepolizumab (Nucala).

One way to begin examining agents’ relative efficacy is through adjusting patient populations recruited in the trials, Casale told MD Magazine.

"In the study of patients that have been involved in omalizumab trials, we looked at patient characteristics that were similar to studies using other biologics,” Casale said. “When we adjusted, for example, for starting blood eosinophil levels, one could see a similar pattern to several of the other biologics."

In addition to incorporating a range of the patients' characteristics, from tobacco usage to asthma duration and spirometry values, Casale and colleagues identified three factors to focus on for potential interactive effects with treatment response: long-acting beta-agonist (LABA) usage, blood eosinophil levels, and asthma hospitalization in the year before study baseline.

Overall, the rate of exacerbations requiring 3 or more days of systemic corticosteroid treatment was 0.066 in patients treated with omalizumab, a 55% reduction from baseline, versus 0.147 in those given placebo. With the enrichment analysis, exacerbation reduction with omalizumab relative to placebo was found to be more pronounced in patients with higher eosinophil counts (≥300/µL), and with more severe asthma.

The higher severity was defined by history of hospitalization, forced expiratory volume in one second (FEV₁) <65% predicted, requirement for LABA use and requirement for beclomethasone ≥600µg/day.

Enrichment of study populations with patients having more severe symptoms inherently allows for greater efficacy, researchers explained, because it leaves more room for improvement with the treatment intervention.

The inclusion of patients with eosinophilic asthma phenotype was likely to demonstrate response to omalizumab, as the agent has been reported to reduce airway eosinophils as well as peripheral blood eosinophils, researchers wrote.

"Increasing efficacy as blood eosinophils increased with comparative reductions in asthma exacerbations were noted for omalizumab, which was very similar to other biologics used to treat severe asthma," Casale said.

The study, "Response to omalizumab using patient enrichment criteria from trials of novel biologics in asthma," was published online in Allergy last month.

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