Cough is often perceived as one of the most bothersome symptoms in patients with severe asthma.In a post hoc analysis of the phase III MIRACLE trial, benralizumab relieves cough and/or dyspnoea and improves cough-specific health-related quality of life (HRQoL) in individuals with severe eosinophilic asthma (SEA).
“Patients with SEA tend to have poor asthma control, frequent exacerbations, and often rely on high-dose oral corticosteroids … In this analysis, benralizumab reduced cough and/or dyspnoea frequency and improved cough-specific HRQoL more rapidly than placebo in patients with SEA in Asia,” the researchers said.
Compared with the placebo group, the benralizumab group had more patients transitioning to non-frequent cough at week 8 (54 percent vs 39.7 percent; p=0.0051). While the percentages increased over time, these became similar by week 48 (59.3 percent vs 56.7 percent).
Furthermore, 40–50 percent of benralizumab-treated patients reported improvements in cough-related disturbances in the SGRQ*, including pain (45.8 percent), fatigue (40.9 percent), sleep disturbance (50.3 percent), and embarrassment in public at week 8 (48.8 percent). The corresponding percentages in the placebo group were 29, 29.1, 44.7, and 36.4 percent, respectively.
“These early differential numerical improvements in cough-specific HRQoL with benralizumab vs placebo were sustained through week 48,” the investigators said.
Dyspnoea
More benralizumab vs placebo recipients transitioned to non-frequent dyspnoea at week 8 (64.2 percent vs 47.1 percent; p=0.0026), which persisted through week 48 (75.5 percent vs 63.4 percent; p=0.0221). [Ther Adv Respir Dis 2026:20:17534666261471304]
According to the researchers, this effect may have been driven by benralizumab’s eosinophil-depleting mechanism in reducing airway inflammation. Evidence shows that benralizumab-induced eosinophil count (EOS) depletion can alleviate both mucus plugging and structural abnormalities, thus improving airway patency. [Int Arch Allergy Immunol 2023;184:783-791; Int Arch Allergy Immunol 2023;184:243-251]
“These findings suggest that early initiation of benralizumab may be beneficial for restoring airway function and slowing the progression of airway remodeling in patients with SEA,” the researchers said.
Higher inflammatory burden
The improvements with benralizumab were more pronounced in patients with higher inflammatory burden or those with baseline blood EOS ≥300 cells/μL.
In this subgroup, more benralizumab-treated patients transitioned to non-frequent cough compared with placebo recipients at week 8 (55.3 percent vs 37.1 percent; p=0.0027) and week 48 (59.8 percent vs 52.1 percent; p=0.2008). According to the researchers, these likely reflect greater baseline symptom burden and improvement potential rather than a definitional response threshold.
The proportions of participants with improvements from baseline were consistently higher in the benralizumab vs placebo group for the four cough-related SGRQ items across all post-baseline timepoints up to week 48.
These results suggest that a higher baseline blood EOS may be associated with a greater cough-relieving response to benralizumab treatment, which aligns with its mechanism of action in reducing eosinophilic inflammation. [Lancet Respir Med 2023;11:650-662]
The benralizumab group also had more patients who transitioned to non-frequent dyspnoea at week 8 (66 percent vs 45.1 percent; p=0.0031), which persisted through week 48 (76.3 percent vs 60.8 percent; p=0.0188).
The most burdensome symptoms
“Cough is often perceived as one of the most bothersome symptoms in patients with severe asthma, contributing to sleep disturbance, social embarrassment, and other functional impairments,” the researchers said. Dyspnoea is also considered a highly impactful symptom in mild and severe asthma. [Respir Med 2023:207:107098]
Evidence shows that biologics such as benralizumab improve lung hyperinflation in severe asthma. [Respir Med 2024;225:107578; J Asthma Allergy 2021:14:863-871] However, there is insufficient data on the efficacy of biologics in relieving cough and dyspnoea. [Respir Res 2023;24:235]
This analysis used data from the MIRACLE study, which was conducted across 79 centres in China, the Philippines, and South Korea. The study enrolled patients with severe asthma (≥2 exacerbations in the past year) who were on medium- to high-dose ICS/LABA**. A total of 338 participants (mean age 51.65 years, 55 percent women) were randomized 1:1 to SC benralizumab 30 mg (Q4W for the first three doses then Q8W) or placebo for 48 weeks.
“Over 70 percent of the participants had frequent cough at baseline, suggesting that their background maintenance asthma medications and/or treatment adherence prior to study start were insufficient to effectively relieve the cough symptoms,” the researchers said.
“Taken together, our findings support the therapeutic strategy of eosinophil depletion for reducing cough burden and are consistent with guideline recommendations on initiation of biologics based on inflammatory endotypes,” they said. “The results further suggest that, among patients with SEA and concurrent frequent cough, earlier initiation of biologic therapy may help address symptom burden and improve QoL.”
The researchers called for further evaluation using cough-specific clinical endpoints to validate the potential benefits of benralizumab in this setting.