Anti–IL-5Rα antibody improves lung function in an elderly patient with asthma
History, presentation and treatment
A 61-year-old male nonsmoker with good past health reported a yearlong history of on-and-off cough that increased in severity in the last 3 months, when seeking second opinion at our clinic on 1 April 2020. An earlier chest X-ray showed a left lower lung shadow, and a subsequent CT scan revealed a lung mass with mediastinal lymphadenopathies.
Baseline spirometry on 14 April 2020 produced a forced vital capacity (FVC) of 3.45 L and a forced expiratory volume in 1 second (FEV1) of 2.11 L (FEV1/FVC ratio of 61 percent). Relevant baseline blood tests revealed a mildly elevated eosinophil level at 7 percent.
Biopsy of the lung mass and mediastinal lymph nodes confirmed the diagnosis of early-stage lung cancer (ie, stage 1B, adenocarcinoma). The patient underwent a lobectomy to remove the left lower lobe in the same month and remained well after surgery. He was followed up every 6 months.
In March 2021, the patient complained of increasing exertional dyspnoea and impaired exercise capacity (ie, shortness of breath after one flight of stairs), which he first experienced in January 2021 after reportedly having a viral infection (not COVID-19). He also complained of coughing in his sleep and noisy breathing. On physical examination, he exhibited wheezing. Based on these signs and symptoms, he was diagnosed with asthma and was prescribed a fixed-dose combination of an inhaled corticosteroid (ICS) and a long-acting beta-agonist (LABA) (ie, fluticasone furoate 100μg plus vilanterol 25μg).
The patient responded well to treatment, with exercise capacity normalized shortly after treatment initiation. However, spirometry results on 18 March 2021 showed mild airway obstruction without significant bronchodilator response. His FVC remained relatively stable at 3.65 L, but his FEV1 decreased to 1.74 L, which may have been due to the previous lung surgery. Notably, his FEV1/FVC ratio also decreased to 48 percent; it should remain the same even after lung surgery.
The patient was asymptomatic and had relatively controlled asthma after initiating ICS/LABA treatment. However, since he had a very active lifestyle, an eosinophil count check was ordered to see if his lung function could be further improved. On 16 April 2021, relevant laboratory examinations showed an elevated eosinophil level of 13.6 percent. Add-on therapy with an anti–interleukin-5 receptor α (anti–IL-5Rα) agent was considered to further improve his lung function due to the reduced FEV1/FVC ratio, eosinophilia, and lack of significant bronchodilator response.1
On 16 April 2021, the patient started receiving subcutaneous injections of the anti–IL-5Rα agent, benralizumab, at 30 mg for the first three doses (Q4W), followed by Q8W dosing intervals. After about 1 month of benralizumab therapy, his peak expiratory flow rate (PEFR) gradually improved from the baseline value of 350 L/min to 390 L/min. He also reported feeling better. On 6 August 2021, his PEFR further increased to 440 L/min. Lung function tests also showed that his FEV1/FVC ratio had improved to 64 percent (ie, FVC of 3.81 L and FEV1 of 2.43 L), which was approximately the same as his baseline spirometry findings before lobectomy. He was then advised to discontinue the ICS/LABA treatment and remain on benralizumab monotherapy.
In October 2021, the patient continued to be asymptomatic while his PEFR improved to 470 L/min. In November 2021, spirometry results showed an FVC of 3.86 L and an FEV1 of 2.49 L after significant bronchodilator response, which implied active airway inflammation. He resumed the ICS/LABA treatment in addition to benralizumab.
The patient is currently well and has no asthma symptoms. Last seen on 20 May 2022, his most recently reported FVC was 4.61 L and FEV1 was 2.76 L (FEV1/FVC ratio of 60 percent), which are better than his preoperative lung function.
In patients with asthma, lung function tests are essential to confirm the presence of persistent or variable expiratory airflow limitation.1 Although currently recommended treatment adjustments from the 2022 Global Initiative for Asthma (GINA) guidelines are based on assessment of disease control, lung function tests as well as additional investigations such as eosinophil level measurement may reveal relevant actionable information to help further improve lung function in patients with asthma.1-3
Our patient, for instance, appeared to have well-controlled asthma shortly after starting treatment with a
fixed-dose ICS/LABA combination since his symptoms resolved and he was subjectively feeling better. However, spirometry results showed an abnormality
– reduced FEV1/FVC ratio, which indicated a reduction in lung function independent of previous lung surgery and a mild airway obstruction. (Table) Further investigations also revealed that the patient had an elevated eosinophil level of 13.6 percent, suggestive of eosinophilic asthma.1
The goal of asthma treatment is to achieve disease control, which includes symptom improvement and prevention of exacerbations.1 Although our patient was asymptomatic and relatively well, the reduced FEV1 despite bronchodilation is a risk factor for asthma exacerbation.1 Our patient was receiving an ICS/LABA combination, which targets the eosinophilic inflammatory pathway and airway hyperresponsiveness.1,4 However, the findings of eosinophilia, mild airway obstruction and lack of bronchodilator response indicated that his lung function could still be improved and risk of exacerbation further reduced.
The anti–IL-5Rα monoclonal antibody, benralizumab, is currently recommended as an add-on biologic therapy for patients with inadequately controlled severe eosinophilic asthma despite high-dose ICS plus LABA.1,5 Although our patient’s case was not characteristically severe due to the absence of asthma symptoms, the addition of benralizumab resulted in improved lung function, which is consistent with study results involving patients with severe eosinophilic asthma.6,7
In the 1-year, phase III CALIMA trial, the addition of benralizumab to ICS/LABA significantly reduced annual exacerbation rates (Q4W regimen,p=0.0018; Q8W regimen, p=0.0188) and was generally well tolerated by patients with severe, uncontrolled eosinophilic asthma. Benralizumab also significantly improved prebronchodilator FEV1 (Q4W, p=0.0054; Q8W, p=0.0102) and total asthma symptom score (Q8W only, 0.0186) in these patients.6 Similar results were reported in the 1-year, phase III SIROCCO trial, which included patients with severe eosinophilic asthma uncontrolled by high-dose ICS plus LABA.7 The safety results from patients who completed the CALIMA and SIROCCO trials remained consistent through the second year of treatment, with no new consequences of long-term eosinophil depletion and similar incidence of other adverse events.8
In summary, our patient’s experience highlights the importance of going beyond a symptom-based approach in asthma control assessment and treatment adjustment. Spirometry findings and blood tests may provide additional information on what appropriate treatments may be added. In asymptomatic patients with suboptimal lung function and eosinophilia, add-on benralizumab may improve lung function outcomes and reduce the risk of future exacerbations.