NEW ORLEANS – A new analysis suggests However, exacerbation reductions were greatest in patients with high reversibility, and omalizumab only improved lung function significantly in FAO-negative patients with high reversibility.
, of Baylor College of Medicine, Houston, presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from a post hoc analysis of the phase 3 EXTRA study (). This 48-week study enrolled patients who had inadequately controlled, severe asthma despite receiving high-dose inhaled corticosteroids and long-acting beta-agonists.
The patients were randomized to receive omalizumab (n = 427) or placebo (n = 421). Baseline characteristics were similar between the treatment arms.
FAO presence was defined as a postbronchodilator FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) ratio less than 70%. High reversibility was defined as an increase in FEV1 of 12% or greater after albuterol administration.Omalizumab reduced exacerbations regardless of FAO, but the exacerbation relative rate reductions were greatest in FAO-positive and -negative subgroups with high reversibility.
The exacerbation relative rate reductions with omalizumab versus placebo were as follows:
- 24.8% in the overall population.
- 6.0% in FAO-positive patients with low reversibility.
- 59.8% in FAO-positive patients with high reversibility.
- 17.4% in FAO-negative patients with low reversibility.
- 44.3% in FAO-negative patients with high reversibility.
“So bronchodilator reversibility at baseline was … a correlate of more significant exacerbation reduction than … low reversibility,” Dr. Hanania said. “But the fixed airflow obstruction, whether it was present or not, did not really matter.”
As for lung function improvement, omalizumab conferred a marginal benefit for the overall population, but the improvement was “much more significant” in the FAO-negative patients with high reversibility, according to Dr. Hanania.
At week 48, the least-square mean treatment difference (omalizumab vs. placebo) for absolute FEV1 change from baseline was:
- 68 mL in the overall population.
- 17 mL in FAO-positive patients with low reversibility.
- 2 mL in FAO-positive patients with high reversibility.
- 34 mL in FAO-negative patients with low reversibility.
- 104 mL in FAO-negative patients with high reversibility.
“As lung function improvement by omalizumab appeared to be driven by reversibility, asthma with lower reversibility and fixed airflow obstruction may represent a different phenotype,” Dr. Hanania said. “I think this needs to be looked at.”
This research was funded by Genentech and Novartis. Dr. Hanania disclosed relationships with Genentech, Novartis, AstraZeneca, Boehringer Ingelheim, GSK, Regeneron, and Sanofi.
SOURCE: Hanania N et al. CHEST 2019. .