Baseline Factors Can Identify Positive Response to Benralizumab in Severe Asthma

A recent study¹ published in the European Respiratory Journal suggests that in addition to elevated blood eosinophil counts, baseline clinical factors can help identify patients who would potentially be responsive to benralizumab (Fasenra), a monoclonal antibody that targets the interleukin (IL)-5 receptor α and has been shown to reduce exacerbations and improve lung function for patients with severe, uncontrolled asthma with eosinophilic inflammation.

Eosinophilic inflammation of the airways is associated with increased disease severity, exacerbation frequency, and symptom burden, together with decreased lung function. About 10% of patients have severe, uncontrolled asthma, and require high-dosage inhaled corticosteroids (ICSs) plus long-acting β2-agonist (LABA) combination therapy and additional controller medications for disease control, highlighting the need for new treatment options.

Study author Eugene R. Bleecker, MD, and colleagues explain that because eosinophil counts are indirect and lack specificity, methods other than eosinophil counts are needed to identify patients who might benefit from therapies that reduce eosinophilic inflammation by targeting the IL-5 receptor α and anti-IL-5 monoclonal antibodies, which have demonstrated clinical efficacy for patients with severe asthma and evidence of eosinophilic inflammation.

The researchers found that the following baseline factors influenced benralizumab efficacy regardless of patients’ blood eosinophil counts:

• Oral corticosteroid (OCS) use
• Nasal polyposis
• Pre-bronchodilator forced vital capacity (FVC)
• 3 or more prior year exacerbations
• Adult onset of disease (asthma diagnosis) ≥18 years.

The researchers used pooled data from 2 phase 3 studies, SIROCCO and CALIMA, involving over 2500 patients,^2,3 ages 12 to 75 years, with severe, uncontrolled asthma who were randomized 1:1:1 to receive benralizumab 30 mg subcutaneously every 4 weeks (Q4W); every 4 weeks for the first 3 doses, followed by every 8 weeks for the remainder of the treatment period (Q8W); or placebo. All patients were also receiving high-dose ICSs plus LABAs. (Only results for the Q8W dosage of benralizumab are discussed in the present study.)

For patients in the pooled SIROCCO and CALIMA studies who received high-dose ICS/LABA and with blood eosinophil counts ≥300 cells/µL, benralizumab Q8W decreased exacerbations by 42% (P <.001) and increased pre-bronchodilator FEV₁ by 0.14 L (P <.001) relative to placebo. Conversely, patients with none of these features were least responsive to benralizumab Q8W, the researchers note.

The treatment effect of benralizumab administered every 8 weeks was enhanced with each baseline factor for all patients and those with ≥300 eosinophils/µL relative to the overall population. Use of OCS, nasal polyposis, and FVC <65% of predicted value were associated with greater responsiveness to benralizumab Q8W, resulting in a reduced asthma exacerbation rate for patients with <300 eosinophils/µL.

The researchers conclude that there are several clinical characteristics also associated with the severe eosinophilic asthma phenotype that complement baseline blood eosinophil counts in predicting a treatment response to benralizumab for patients with severe, uncontrolled asthma, including OCS use, nasal polyposis, low lung function, history of frequent exacerbations, and adult onset of disease.

“These features are easily assessed by healthcare professionals in an office setting and should help inform clinical decisions on the use of benralizumab for specific patients,” they wrote.

Funding for this study was provided by AstraZeneca.

References

1. Bleecker ER, Wechsler ME, FitzGerald JM, et al. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018;52: pii: 1800936. doi: 10.1183/13993003.00936-2018.
2. Bleecker ER, FitzGerald JM, Chanez P, et al; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388:2115-2127. doi: 10.1016/S0140-6736(16)31324-1.
3. FitzGerald JM, Bleecker ER, Nair P, et al; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388:2128-2141. doi: 10.1016/S0140-6736(16)31322-8.