The anti-interleukin-5 receptor alpha monoclonal antibody benralizumab significantly reduced the rates of severe exacerbations (SevEx) and asthma worsening episodes (AWE) in patients with severe asthma, leading to a reduction in the risk of overall CompEx* events, according to a post hoc analysis of the phase III SIROCCO** and CALIMA*** trials presented at ATS 2019.

The cohort comprised 1,039 participants ≥16 years old with baseline blood eosinophil counts ≥300 cells/µL who received benralizumab 30 mg or placebo every 8 weeks (first three doses every 4 weeks). [ATS 2019, abstract A7087/P509]

Evaluation of each CompEx component revealed that benralizumab-treated patients had lower incidences of SevEx events in both the SIROCCO and CALIMA trials (34.1 percent and 36.3 percent, respectively) vs those who were treated with placebo (52.0 percent and 50.2 percent, respectively), corresponding to hazard ratios (HRs) of 0.56 (95 percent confidence interval [CI], 0.42–0.73) and 0.66 (95 percent CI, 0.51–0.85) for SIROCCO and CALIMA, respectively.

AWE rates were also reduced with benralizumab vs placebo in both SIROCCO (21.3 percent vs 34.7 percent) and CALIMA (19.1 percent vs 30.6 percent), corresponding to HR values of 0.57 (95 percent CI, 0.47–0.80) and 0.58 (95 percent CI, 0.41–0.83).

The incidence of at least one CompEx event among benralizumab recipients was similar in SIROCCO and CALIMA (43.0 percent and 43.1 percent, respectively), which was lower than those who received placebo (63.3 percent and 58.2 percent, respectively). These values corresponded to 45 percent and 35 percent risk reductions in CompEx events with benralizumab as reflected by the HR values (HR, 0.55, 95 percent CI, 0.43–0.71 and HR, 0.65, 95 percent CI, 0.51–0.82 for SIROCCO and CALIMA, respectively).

Annualized event rates remained lower among benralizumab recipients vs placebo across all study groups in both SIROCCO (1.15 vs 2.63, rate ratio [RR], 0.39 for CompEx; 0.67 vs 1.69, RR, 0.36 for SevEx; and 0.62 vs 1.27, RR, 0.40 for AWE) and CALIMA studies (0.88 vs 1.73, RR, 0.45; 0.60 vs 0.99, RR, 0.57; and 0.39 vs 0.91, RR, 0.37, respectively).

SevEx are rare asthma worsening events requiring episodic treatment with systemic corticosteroids and/or hospitalization. Albeit rare, reducing the rate of SevEx is crucial for evaluating the efficacy of asthma therapies, noted the researchers. CompEx events occur more frequently than SevEx events; thus, treatment effect may be observed earlier with CompEx than with SevEx alone, they added.

“[Our findings show that] benralizumab substantially reduced the risk of overall CompEx events,” said the researchers. “These results highlight that benralizumab treatment in patients with severe asthma reduces episodes of asthma worsening, as defined by changes in peak flow, reliever medication use, and symptoms that are not captured in the standard definition of SevEx.”

Moreover, the researchers noted that the findings further substantiate the role of CompEx as an important measure for evaluating the efficacy of asthma treatments in clinical trials.