Impact of Body Mass Index on Efficacy of Benralizumab in Patients with Severe, Uncontrolled Eosinophilic Asthma: Pooled Analysis of the SIROCCO and CALIMA Trials

Introduction Obesity correlates with increased asthma severity and poor control (Respirology. 2017;22 : 651 – 61). Benralizumab, a humanized, afucosylated, anti–interleukin-5 receptor α monoclonal antibody, rapidly depletes eosinophils, reduces exacerbations, and improves daily symptoms for severe, uncontrolled eosinophilic asthma patients (pts). We evaluated the impact of body mass index (BMI) on benralizumabʼs efficacy.

Methods In a post-hoc pooled analysis of the Phase III SIROCCO (48 wks; Lancet. 2016;388 : 2115 – 27) and CALIMA (56 wks; Lancet. 2016;388 : 2128 – 41) trials, pts aged ≥ 12 years on high-dosage ICS/LABA with baseline (BL) blood eosinophils ≥ 300 cells/µL (full analysis set) received benralizumab 30 mg SC every 4 (Q4W; n = 503) or 8 wks (Q8W; first 3 doses Q4W; n = 490), or placebo (n = 496). Adult pts (aged ≥ 18 years) were categorized as normal/underweight (BMI < 25 kg/m²), overweight (BMI ≥ 25–<30 kg/m²), or obese (BMI ≥ 30 kg/m²). Efficacy outcomes included annual exacerbation rate and change from BL to end of treatment in prebronchodilator FEV₁ by BMI categories.

Results At BL, age, lung function, smoking history, and oral corticosteroid use were similar across all treatment and BMI groups (table). There was a trend toward lower BL eosinophil counts with increasing BMI. Improvements in exacerbation rates and lung function were similar between Q4W and Q8W groups relative to placebo for respective BMI groups (table). Benralizumab treatment was associated with improvements in exacerbation rates vs. placebo for normal/underweight and overweight groups (Q8W, rate ratio 0.51 and 0.43, respectively, nominal p ≤ 0.0003), with numerical improvements observed with both dosages vs. placebo for the obese group. Increases in prebronchodilator FEV₁ from BL were greater with benralizumab vs. placebo for normal/underweight and overweight groups (Q8W: 0.148 and 0.214 L, respectively, nominal p ≤ 0.0199), with numerical improvements observed with both dosages vs. placebo for the obese group.

Conclusion For pts with severe, uncontrolled eosinophilic asthma, benralizumab decreased asthma exacerbations and increased lung function regardless of BMI value, with improvements numerically favoring benralizumab for pts with severe asthma and comorbid obesity. FEV₁ improvements were less robust for obese pts.