Martínez‑Rivera et al. BMC Pulm Med (2021) 21:35 https://doi.org/10.1186/s12890-021-01397-7 CASE REPORT Open Access Rapid effect of benralizumab in exacerbation of severe eosinophilic asthma associated with eosinophilic granulomatosis with polyangiitis Carlos Martínez‑Rivera1*, Ignasi Garcia‑Olivé1, Blanca Urrutia‑Royo1, Maria Basagaña‑Torrento2, Antoni Rosell1 and Jorge Abad1 Abstract Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease that is associated with severe uncon‑ trolled eosinophilic asthma. Eosinophils play an important pathogenic role in the development of both diseases. Benralizumab is an antieosinophilic monoclonal antibody that binds to the α subunit of the human interleukin 5 receptor that is expressed on the surface of the eosinophil and basophil. We present the first case of rapid improve‑ ment in symptoms and lung function during admission for exacerbation of a severe eosinophilic asthma associated with EGPA. Case presentation: A 57-year-old man diagnosed with severe eosinophilic asthma associated to EGPA was admit‑ ted to the Pulmonology Department due to severe bronchospasm. At admission he presented 2300 eosinophils/µl. Despite intensive bronchodilator treatment, intravenous methylprednisolone at a dose of 80 mg/d, oxygen therapy, and budesonide nebulization, the patient continued to present daily episodes of bronchospasm. Ten days after admission, with blood eosinophil levels of 1700 cells/µl, benralizumab 30 mg sc was administered. That day, the Forced Expiratory Volume in the first second (FEV1) was 28% of the theoretical value (1150 ml). AT three days, FEV1 increased to 110 ml (31%). On the 9th day FEV1 was 51% (2100 ml). The blood eosinophil level on the 9th day was 0 cells/µl. Conclusions: The rapid improvement of FEV1 is in line with studies based on clinical trials that found improvement after two days in peak flow and one phase II study that showed rapid response in exacerbation of asthma in the emer‑ gency room. The antieosinophilic effect at 24 h and the effect in different tissues determine the rapid improvement and the potential advantage of benralizumab in the treatment of EGPA. This case suggests the usefulness of benrali‑ zumab in patients with EGPA and eosinophilic severe asthma who show bronchospasm refractory to conventional treatment during a hospitalization due to asthma exacerbation. Keywords: Severe eosinophilic asthma, Benralizumab, Eosinophilic granulomatosis with polyangiitis, Pulmonary function Background *Correspondence: carlosmartinezrivera.cmr@gmail.com Eosinophilic granulomatosis with polyangiitis (EGPA) 1 Pneumology Department, Hospital Universitari Germans Trias I Pujol, is a disease that causes small to medium sized vessel CIBERES, Universitat Autònoma de Barcelona, Carretera del canyet sn, 08916 Badalona, Barcelona, Spain necrotizing vasculitis and affects many organs to vary- Full list of author information is available at the end of the article ing degrees, including the lungs, and is associated with © The Author(s) 2021. 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The Creative Commons Public Domain Dedication waiver (http://creat​iveco​ mmons​.org/publi​cdoma​in/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Martínez‑Rivera et al. BMC Pulm Med (2021) 21:35 Page 2 of 4 severe uncontrolled eosinophilic asthma. Eosinophils Historically, the maximum levels of eosinophils in the play an important role in the development of both pathol- blood have been 20,000 cells/µl. Upon admission, he ogies. The pathogenesis of EGPA is not well known. It is presented 2300 cells/µl. One month earlier, the patient believed to be the product of the interaction of genetic was admitted to the Rheumatology Department of our factors and exposure to environmental factors such as center and required treatment with 3 boluses of 500 mg infectious agents, birds, cocaine or medicines. As a result of methylprednisolone. He had been on prednisone an inflammatory response is unleashed involving eosino- 60 mg/d from then until the current admission. phils and where it is believed that the clonal expansion of The patient was admitted to the Pulmonology Ser- TCD8 cells and to a lesser degree TCD4 cells can play a vice due to severe Bronchospasm with respiratory rate role [1]. of 35 rpm, bilateral hypophonesis and respiratory fail- Benralizumab is an antieosinophilic monoclonal anti- ure (pH: 7.36; ­pCO2: 51 mmHg; pO2: 51 mmHg; H ­ CO3: body that binds to the α subunit of the human interleu- 28.8 mmol/L; Sat. ­O2: 88.6%). His general condition kin 5 receptor (IL-5Rα) that is expressed on the surface was poor, and he presented dyspnea with inability to of the eosinophil and basophil. Through an antibody- the supine. Intensive bronchodilator treatment and dependent cellular cytotoxicity mechanism and because systemic corticosteroids were started, with which the of its high affinity for FcγRIII receptors in immune effec- patient improved rapidly. After a 6 h stay in the emer- tor cells such as natural killer (NK) cells, benralizumab gency dept., admission to the conventional ward was produces apoptosis of eosinophils [2]. The direct action decided since he was stable with some persistent scat- mechanism of benralizumab on the eosinophils involved tered wheezing, with O ­ 2 Saturation of 96% under O ­2 in systemic inflammation [3] suggests that it could be venturi typo oxygen mask delivering 28% oxygen. effective in improving asthma in patients with EGPA. Despite bronchodilator treatment, intravenous meth- It is known that benralizumab can produce rapid ylprednisolone at a dose of 80 mg /d, oxygen therapy, improvement in lung function (8) and that it may be use- and budesonide nebulization, the patient continued to ful for treating EGPA (11), in stable situations. But there present daily episodes of bronchospasm accompanied is no evidence on the efficacy in these diseases during by a refractory cough during the first 10 days of admis- an exacerbation. We report a case of a patient admitted sion. We assumed that persistent eosinophilic inflam- to the hospital for exacerbation of a Severe Eosinophilic mation despite corticosteroid treatment played an Asthma associated with EGPA refractory to conventional important role in his incomplete recovery, thus propos- treatment, who presented significant improvement in ing a rapid eosinophilic suppression pharmacothera- symptoms and lung function two days after starting the peutic alternative. administration of benralizumab during hospitalization. Ten days after admission, with blood eosinophil lev- els of 1700 cells/µl, benralizumab 30 mg sc was admin- Case presentation istered. Spirometry that day showed, prior to the start Our patient is a 57-year-old male diagnosed with asthma of treatment, a FEV1 of 28% of the theoretical value 4 years ago in another center and treated with a combi- (1150 ml). nation of a high-dose inhaled corticosteroid (budesonide Within three days of starting benralizumab treat- 1280 µg/d) and a long-acting β2-adrenergic agonist, for- ment, the patient had less dyspnea, the cough improved moterol 36 µg/d (ICS/LABA) and a long-acting antimus- significantly, as well as his condition. FEV1 showed carinic (LAMA), tiotropium 5 µg/d. He did not report increases of 110 ml (31% theoretical value). On the daily symptoms but required treatment with courses sixth day after starting benralizumab, the FEV1 of oral corticosteroids 3–4 times annually for the last improved to 45% (1830 ml) of the theoretical value and 4 years. Six months before admission he had Forced there were no new episodes of dyspnea plus wheezing. Expiratory Volume in the first second (FEV1) of 58% On the 9th day the clinical improvement persisted and (2388 ml). the FEV1 was 51% of the theoretical one (2100 ml), rep- Three months prior to the presentation discussed resenting an improvement of 985 ml compared to the the patient was diagnosed of EGPA with pulmonary first spirometry. At that time, he had a blood eosinophil involvement in the form of multiple bilateral ground level of 0 cells/µl. Ten days after starting benralizumab, glass infiltrates, chronic pansinusitis and cutaneous the patient was discharged and ordered to gradually vasculitis in the extremities and buttocks, diagnosis decrease the treatment with oral corticosteroids in the by cutaneous biopsy showing fibrinoid necrosis and next 20 days until maintaining 5 mg/d of prednisone. perivascular eosinophilic infiltrate. He had high levels No adverse effects were reported. The patient explained of p antineutrophil cytoplasmic antibody (pANCA)(1). that, from his point of view, he had never experienced such a clear improvement as now. Martínez‑Rivera et al. BMC Pulm Med (2021) 21:35 Page 3 of 4 Fig. 1 Evolution of lung function according to prebronchodilator FEV1 (% theoretical value and ml) after the first dose of benralizumab 30 mg sc and after two days following the second dose Discussion and conclusions eosinophilic bronchial asthma and EGPA, associ- The rapid improvement in lung function in this patient ated with a total depletion of eosinophils in the blood from a baseline prebronchodilator FEV1 value of 1150 ml a few days after starting treatment. This suggests that was maintained after discharge. One month after start- in patients with this profile who show a bronchospasm ing treatment and three days after the administration of refractory to conventional treatment during admission, the second dose of benralizumab, a FEV1 of 2950 ml was the start of treatment with benralizumab could be a reached (71% of the theoretical value) (Fig. 1). In line with therapeutic option to consider. these data, a study based on three clinical trials reported improvement after two days in peak flow [6]. This Abbreviations increase was accompanied by a significant improvement EGPA: Eosinophilic granulomatosis with polyangiitis; IL-5Rα: α Subunit of the in forced vital capacity (FVC) that increased by 1250 ml human interleukin 5 receptor; NK: Natural killer; ICS: Inhaled corticosteroid; from baseline, which illustrates the impact that ben- LABA: Long-acting β2-adrenergic agonist; LAMA: Long-acting antimuscarinic; pANCA: P antineutrophil cytoplasmic antibody; FEV1: Forced expiratory ralizumab causes on lung hyperinflation. High levels of volume in the first second. eosinophils in the blood are associated with airway limi- tations [7] and it seems likely that the antieosinophilic Acknowledgements Not applicable effect at 24 h of this monoclonal antibody may be related to the rapid increase in respiratory function parameters, Authors’ contributions as described by pivotal studies [8] and confirmed in real CMR was implicated in conception, data generation, analysis, revision and approval. IGO, BUR, MBT, ARG, JAC was implicated in data generation, analysis, life studies with benralizumab [9]. On the other hand, in revision and approval. All authors have read and approved the manuscript. a phase II trial, eligible subjects in the emergency room with an exacerbation of asthma had a rapid response with Funding No funding has been required for the present study. benralizumab, with the hypothesis that it may act as an adjunct treatment to oral corticosteroids in the treatment Availability of data and materials of exacerbations and prevent recurrence of the same [4]. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Likewise, the effect on eosinophils in different tis- sues involved in the inflammatory response determine a Ethics approval and consent to participate potential advantage of benralizumab in the treatment of Not applicable. EGPA. Studies are being carried out that will explore the Consent for publication efficacy and safety of benralizumab in the treatment of Written informed consent was obtained from the patient for publication of this condition [10] and that will validate the results expe- this case report and any accompanying images. rienced in some patients [5, 11]. Competing interests Our case shows a rapid response in both symptoms The authors declare that they have no competing interests. and lung function in a patient with exacerbated severe Martínez‑Rivera et al. BMC Pulm Med (2021) 21:35 Page 4 of 4 Author details 6. Chupp G, Lugogo NL, Kline JN, Ferguson GT, Hirsch I, Goldman M, 1 Pneumology Department, Hospital Universitari Germans Trias I Pujol, Zangrilli JG, et al. Rapid onset of effect of benralizumab on morning CIBERES, Universitat Autònoma de Barcelona, Carretera del canyet sn, peak expiratory flow in severe, uncontrolled asthma. 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