Case Report: Acute effect of benralizumab on asthma exacerbation without concomitant corticosteroid use

Patient information and medical history

We present the case of a 59-year-old non-smoker Caucasian female, lawyer, with a history of allergic asthma since childhood. She had no pets at home.

Timeline of patient's clinical evolution with diagnostic tests and treatments is shown in Figure 1.

Figure 1. Case report timeline following CARE guidelines.

LAMA, long acting muscarinic agonist; LTRA, leukotrienes receptor antagonist; Q4W: every four weeks.

The patient had a body mass index within the normal range, chronic rhinosinusitis without nasal polyposis, and gastro-esophageal reflux under pharmacological control.

Her basal asthma regimen over the years was budesonide/formoterol 160 mcg/4.5 mcg, four puffs/day, with good treatment adherence and correct inhalation technique.

Over the past years, despite her adequate adherence to her maintenance regimen, the patient experienced a gradual worsening of her asthma symptoms, together with a progressive decline of her lung function and an increasing number of exacerbations, some of which required hospitalization. Therefore, after a pulmonologist consultation, combined treatment with a long-acting muscarinic antagonist (LAMA; 2.5 mcg tiotropium Respimat inhaler, two puffs daily), theophylline (300 mg tablets, bis in die) and a leukotriene receptor antagonist (montelukast, 10 mg daily) were added to her maintenance treatment regimen.

The patient’s adherence to both inhaled (ICS + LABA and LAMA) and oral (theophylline and montelukast) therapy continues to be very good, due to her fear of possible need for intravenous/oral steroids in case of non-adequate adherence.

Initial presentation, diagnostic tests and treatment

In March 2015, she was referred to our outpatient respiratory clinic at Policlinico Vittorio-Emanuele di Catania, Italy, due to the persistence of asthma symptoms despite the therapy. Pulmonary function tests showed a forced vital capacity (FVC) of 78% of predicted value (2620 mL), and a forced expiratory volume in one second (FEV₁) of 55% of predicted value (1400 mL), with a post-bronchodilator (after 400 mcg of salbutamol) increase in FEV₁ of 24% (1990 mL).

She showed sensitization to multiple inhalant allergens by skin prick tests (house dust mites, dog and cat dander, and Parietaria judaica), high serum total IgE levels (201 IU/mL), high blood eosinophils count (670 cells/µL) and high fraction of exhaled nitric oxide (FeNO; 51 ppb). She complained of frequent exacerbations of her asthma symptoms and recurrent hospital admissions over the past year (nearly one/month) and, therefore, we classified her as severe refractory asthma according to Global Initiative for Asthma (GINA) guidelines⁴, after excluding other respiratory diseases that may share common clinical manifestations with severe asthma, as recommended by ERS/ATS guidelines⁵.

Moreover, the patient had always been reluctant to use systemic corticosteroids, referring to an almost immediate appearance of urinary retention, so she refused the proposed short course of oral corticosteroids. Therefore, we started treatment with omalizumab (300 mg via subcutaneous injections administered every four weeks).

Subsequent presentations, diagnostic tests and treatments

We further evaluated our patient every four weeks, and she reported a dramatic reduction in the number and severity of exacerbations (nearly 50% less) and the number of hospitalizations overall, without using systemic steroids. Still, she described persistence of respiratory symptoms and poor asthma control with the need of a salbutamol inhaler at least five times a day, despite the maintenance and the biologic therapy. At her follow-up visit after one year from the first dose of omalizumab, her Asthma Control Test (ACT) score was 8, her FeNo was 33 ppb, and her pulmonary function tests showed an FEV₁ of 73% of predicted value (1860 mL) and FVC of 90% of predicted value (3030 mL), an FEV₁ / FVC of 61% and a positive post-bronchodilatation test response, with FEV₁ reaching 85% (+ 12%) and 2105 mL. She underwent a chest computed tomography scan, revealing diffuse bronchiectasis; therefore, she started long-term azithromycin and airway clearance therapy on top of her usual maintenance treatment. The patient still achieved partially controlled asthma with treatment optimization.

In January 2019, she presented to the emergency department for a new severe exacerbation characterized by whistling dyspnea, greenish sputum, and acute respiratory failure, and required hospitalization.

During the hospital stay, her sputum cytological analysis showed 17% of eosinophils out of a total count of 250,000 cells/mL, and her blood tests exhibited an elevated peripheral eosinophilic count (470 cells/µL). Pulmonary function tests revealed an FEV₁ of 49% of predicted, FVC of 72% of predicted and FEV₁ / FVC of 57.4%. She started intravenous (IV) theophylline (240 mg intravenous slow bolus followed by a continuous infusion of 0.5 mg/kg/h), IV piperacillin/tazobactam (4.5 g every eight hours), IV corticosteroids (40 mg of methylprednisolone), and oxygen (nasal cannula 2 liters/minute) on top of her maintenance therapy, with progressive symptoms relieved. At discharge, we proposed a switch from omalizumab to mepolizumab, but the patient refused.

On November 4, 2019, she presented for a regular outpatient visit and complained of a worsening of her usual respiratory symptoms, presence of wheezing, reduced tolerance to physical activity, abundant purulent sputum, and frequent nocturnal awakenings. She had taken 25+ puffs of salbutamol to alleviate her chest tightness. Her oxygen saturation was 91% at rest.

Pulmonary function tests showed an FEV₁ of 61% of predicted value (1480 mL), FVC of 74% of predicted value (2410 mL), and FEV₁ / FVC of 61%. A post-bronchodilatation test FEV₁ reached 70% (+9%) and 1700 mL. Her ACT score was 6. She also underwent blood tests, showing elevated eosinophils (390 cells/µL) and her FeNo was 60 ppb.

We proposed a short course of steroids, but she refused to take them due to the fear of urinary retention; she also refused hospitalization. Therefore, as a rescue solution, and due to the presence of elevated eosinophils, we decided to switch omalizumab to benralizumab (30 mg by subcutaneous injection every four weeks for the first three doses, and then every eight weeks thereafter) on top of her maintenance therapy. The same day the patient started the first administration of 30 mg subcutaneous injection of benralizumab.

Follow-up and outcomes

At a telephone follow-up after 24 hours, she reported a significant improvement in her asthma symptoms with the almost total disappearance of sputum, absence of nocturnal awakening, and noticeable reduction of dyspnea, which made her stop rescue medication. At her 48 hours follow-up visit, the physical examination revealed a dramatic decrease in whistles as compared to the day before. The FEV₁ was 80% of predicted value (1940 ml, +19% compared to two days before), FVC was 88% of predicted value (2890 ml, +14% compared to two days before) and FEV₁ / FVC was 67% (+6%). Oxygen saturation has improved too, reaching 98% at rest, and her blood test showed complete depletion of eosinophils in peripheral blood. After four weeks, she returned to our outpatient service for administration of the second dose of benralizumab. She described good control of respiratory symptoms within the last month with no exacerbations, nocturnal awakening, nor sputum, and only occasional use of salbutamol. She did not report any adverse effects. Her blood count continued to show complete eosinophils depletion. Pulmonary function tests showed a further increase in lung function: an FEV₁ of 98% of predicted value (2360 ml), FVC of 94% of predicted value (3140 ml), and FEV₁ / FVC 75%. Her ACT reached a score of 18, her highest result ever and her FeNo was 47 ppb. Based on these excellent results the patients was then prescribed with benralizumab 30 mg every four weeks for the following two doses and then every 8 weeks, with the indication of performing a blood test to evaluate the blood eosinophils count before each biologic dose administration.