Next Article in Journal
Targeting Inflammasome Activation in COVID-19: Delivery of RNA Interference-Based Therapeutic Molecules
Next Article in Special Issue
Biologics in Severe Eosinophilic Asthma: Three-Year Follow-Up in a SANI Single Center
Previous Article in Journal
Prostaglandin F2 and EP2 Agonists Exert Different Effects on 3D 3T3-L1 Spheroids during Their Culture Phase
Previous Article in Special Issue
Real-Life Effectiveness of Mepolizumab on Forced Expiratory Flow between 25% and 75% of Forced Vital Capacity in Patients with Severe Eosinophilic Asthma
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Biomedicines
Volume 9
Issue 12
10.3390/biomedicines9121822
biomedicines-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy

by
Corrado Pelaia
1,
Claudia Crimi
2,
Santi Nolasco
2,
Giovanna Elisiana Carpagnano
3,
Raffaele Brancaccio
4,
Enrico Buonamico
3,
Raffaele Campisi
2,
Claudia Gagliani
5,
Vincenzo Patella
4,
Girolamo Pelaia
1,*,
Giuseppe Valenti
5 and
Nunzio Crimi
2
1
Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
2
Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
3
Department of Basic Medical Sciences, Neuroscience and Sense Organs, Section of Respiratory Disease, University “Aldo Moro” of Bari, 70121 Bari, Italy
4
Division of Allergy and Clinical Immunology, Department of Medicine, “Santa Maria della Speranza” Hospital, 84091 Battipaglia, Italy
5
Allergology and Pulmonology Unit, Provincial Outpatient Center of Palermo, 90100 Palermo, Italy
*
Author to whom correspondence should be addressed.
Biomedicines 2021, 9(12), 1822; https://doi.org/10.3390/biomedicines9121822
Submission received: 17 October 2021 / Revised: 28 November 2021 / Accepted: 30 November 2021 / Published: 3 December 2021
(This article belongs to the Special Issue Molecular Targets for Biological Therapies of Severe Asthma)
Browse Figures
Review Reports Versions Notes

Abstract

:
Background. The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. Patients and methods. Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. Results. In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p < 0.01), rescue medication need (p < 0.001), asthma control test (ACT) score (p < 0.05), forced expiratory volume in the first second (FEV1) (p < 0.05), and blood eosinophil count (p < 0.0001). Furthermore, with respect to the end of omalizumab treatment, the score of sino-nasal outcome test-22 (SNOT-22) significantly decreased after therapy with benralizumab (p < 0.05). Conclusion. The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment.

1. Introduction

Severe asthma includes several phenotypes driven by complex cellular and molecular pathogenic networks defined as endotypes [1,2,3]. In particular, the phenotypic/endotypic characterization of asthma is mainly based on the distinction between type 2 (T2-high) and non-type 2 (T2-low) immune-inflammatory traits [4,5,6]. Type 2 asthma is predominantly sustained by bronchial eosinophilic inflammation, induced by either allergic or non-allergic mechanisms [7,8]. Actually, most cases of severe asthma are underpinned by airway eosinophilia [9,10]. The key cells implicated in the onset, progression, and worsening of type 2 asthma are T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells (ILC2), which release high amounts of interleukins (IL)-4 (IL-4), -13 (IL-13), and -5 (IL-5) [11,12,13]. IL-4 and IL-13 promote the synthesis of immunoglobulins E (IgE) [14]. IL-13 also induces goblet cell metaplasia, airway hyperresponsiveness, and proliferation of bronchial smooth muscle cells [15,16]. Moreover, IL-13 enhances the expression of the inducible isoform of nitric oxide synthase (iNOS), thereby stimulating the airway epithelium to produce nitric oxide (NO), with a consequent increase of fractional NO in exhaled breath (FeNO) [17]. IL-5 is essential for maturation, survival, and degranulation of eosinophils [18].
Hence, IgE, blood eosinophils and FeNO are currently considered as useful biomarkers of type 2 asthma, being also utilized to guide the choice of the most appropriate biological therapy for severe disease [1]. Indeed, IgE-driven positivity of skin prick test (SPT) to perennial allergens favours the prescription of anti-IgE treatment, whereas high blood eosinophil counts predict a good therapeutic response to either anti-IL-5 or anti-IL-5-receptor drugs, and high FeNO levels suggest the recommendation of a dual IL-4/IL-13 receptor blocker [19,20,21]. Despite such a quite schematic scenario, in clinical practice many patients with severe asthma can be eligible to more than one biologic because they express overlapping phenotypes [21,22,23]. For example, allergy and eosinophilic inflammation often coexist in the same subject, thus making him/her potentially responsive to either omalizumab, mepolizumab, or benralizumab [8,24].
Omalizumab is a humanized monoclonal antibody which specifically binds to the two Cε3 domains of the constant region of human IgE, thus preventing their interactions with both high affinity (FcεRI) and low affinity (FcεRII/CD23) IgE receptors [25,26]. Therefore, omalizumab effectively inhibits all IgE-dependent pathogenic effects occurring at level of immune/inflammatory and structural cells of the airways [26]. Both randomized controlled trials (RCT) and real-life clinical studies have clearly shown that omalizumab is very effective in improving several clinical and functional parameters related to severe asthma, thus positively impacting on disease exacerbations and airflow limitation [26,27,28,29,30,31,32]. A recent real-life observation has also shown that omalizumab can be very useful to control severe allergic asthma even during the COVID-19 pandemic [33]. However, some allergic patients with severe asthma who are partially or completely unresponsive to omalizumab may benefit from a therapeutic switching to mepolizumab [34,35,36,37,38].
Mepolizumab is a humanized IgG1/κ monoclonal antibody which selectively ligates IL-5, thus inhibiting its interaction with the α subunit of the IL-5 receptor (IL-5Rα) [39]. Both RCT and real-world experiences, carried out in patients with severe eosinophilic asthma, demonstrated that mepolizumab successfully decreases asthma exacerbations and blood eosinophils, as well as improves lung function and reduces the intake of oral corticosteroids (OCS) [39,40,41]. Moreover, in real life, mepolizumab has been shown to exert similar therapeutic effects in subjects with either allergic or non-allergic severe eosinophilic asthma [42].
Differently from mepolizumab, the humanized IgG1/κ monoclonal antibody benralizumab specifically binds through the Fab fragments to IL-5Rα, thereby impeding its occupancy by the natural ligand IL-5 [43,44,45]. Additionally, via the constant Fc portion benralizumab interacts with the FcγRIIIa receptor expressed by natural killer (NK) cells, thus promoting the release of proapoptotic proteins such as granzymes and perforins, which induce eosinophil apoptosis by the so-called mechanism of antibody-dependent cell-mediated cytotoxicity (ADCC) [43,44,45]. Both RCT and real-life reports have documented that benralizumab, utilized in subjects with either allergic or non-allergic severe eosinophilic asthma, significantly improves symptom control, disease exacerbations, lung function, OCS dependence, and blood eosinophilia [43,44,45,46,47,48,49,50,51]. However, the possibility of a therapeutic shift from omalizumab to benralizumab has been poorly investigated so far.
Therefore, on the basis of the above considerations, we decided to evaluate, within a real-life context, the potential benefits of a therapeutic shift to benralizumab, implemented in allergic patients with severe eosinophilic asthma, not satisfactorily controlled by a previous treatment with omalizumab.

2. Patients and Methods

2.1. Study Design and Endpoints

We performed a real-life, retrospective, multicenter study including adult outpatients (≥18 years old) with severe persistent allergic and eosinophilic asthma, uncontrolled despite the add-on biological treatment with omalizumab, and thus switched to benralizumab. These subjects referred to five Respiratory and Allergology Units of Southern Italy (Bari, Battipaglia, Catania, Catanzaro, and Palermo). All enrolled patients met the European Respiratory Society (ERS)/American Thoracic Society (ATS) criteria that define severe uncontrolled asthma [52].
At baseline (before any biological therapy), all 20 patients, also including 9 subjects complaining of chronic rhinosinusitis with nasal polyps (CRSwNP), exhibited high blood eosinophil counts and experienced frequent asthma exacerbations and an inadequate symptom control, thus needing high dosages of inhaled corticosteroids (ICS)/long-acting β2-adrenergic agonists (LABA) combinations, eventually associated with long-acting muscarinic antagonists (LAMA). Such patients had total serum IgE levels included within the range of 30–1500 IU/mL, as required by the Italian Drug Agency (AIFA), and they were also characterized by SPT positivity versus perennial aeroallergens. Therefore, omalizumab was prescribed and administered every 2 or 4 weeks, according to body weight and serum IgE levels. After a treatment period of at least 12 months, patients were shifted to benralizumab because of their unsatisfactory clinical response to anti-IgE therapy. We chose such a relatively long period of initial treatment, because it has been interestingly observed that the onset of a late response to omalizumab can be experienced by some patients even 48 weeks after starting anti-IgE therapy [53]. Therefore, a clinical evaluation restricted to only 3–6 months carries the risk of considering as a non-responder a potential late-responder to omalizumab [53]. Omalizumab failure was defined after at least 12 months of add-on therapy as lack of effectiveness, featured by recurrent asthma exacerbations and/or uncontrolled symptoms. Indeed, a clinically satisfactory response to any biological treatment for severe asthma should primarily provide an almost complete prevention of disease exacerbations. Because many severe asthmatic patients complain of very frequent exacerbations, even halving these events is often not enough to improve the overall quality of life. Benralizumab was prescribed according to current eligibility indications, with a regimen schedule consisting of a single subcutaneous injection of 30 mg every 4 weeks for the first three times, followed by the same dosage given every 8 weeks thereafter. Each subject had blood eosinophil levels higher than 300 cells/μL before starting benralizumab.
The main aim of this real-life investigation was to evaluate the effects of benralizumab on clinical, functional, and laboratory parameters in patients with severe type 2 asthma previously treated with omalizumab. The numbers of asthma exacerbations and hospitalizations, the use of short-acting β2-agonist (SABA) rescue medications, as well as prednisone intake, asthma control test (ACT) score, forced expiratory volume in the first second (FEV1), and blood eosinophil counts were recorded at baseline, after at least 12 months of omalizumab therapy (pre-shift), and at least 12 months after the first injection of benralizumab. Moreover, the sino-nasal outcome test-22 (SNOT-22) questionnaire was administered to patients with allergic CRSwNP. SPT was judged to be positive when the wheal area was equal to or larger than that one caused by histamine. Spirometry was performed according to ATS/ERS guidelines [54].
We enrolled 20 patients, including 13 females and 7 males, with a mean age of 52.85 ± 9.39 years, and a mean BMI of 23.47 ± 3.54 Kg/m2. The mean age of asthma onset was 31.40 ± 14.34 years. Mean baseline FEV1 was 62.47 ± 13.84% of predicted value. Baseline patient characteristics are summarized in Table 1. Fifteen patients (75%) were using LAMA, and 14 (70%) were taking leukotriene receptor antagonists (LTRA). With regard to asthma comorbidities, 11 subjects (55%) had gastro-esophageal reflux disease (GERD), 9 (45%) suffered from CRSwNP, 7 (35%) had bronchiectasis, 3 (15%) complained of atopic dermatitis, and 2 (10%) suffered from obstructive sleep apnea syndrome (OSAS).
The present observational study met the standards of Good Clinical Practice (GCP) and the principles of the Declaration of Helsinki. All recruited patients signed a written informed consent. Our study was also carried out in agreement to what decided by the local Ethical Committee of Calabria Region (Catanzaro, Italy; document n. 257—15 July 2021).

2.2. Statistical Analysis

Prism Version 9.1.2 (GraphPad Software Inc., San Diego, CA, USA) was used to statistically analyze study results. Median values with interquartile range (IQR) were used to express skewed data distributions, while normally distributed data were expressed as mean ± standard deviation (SD). The normality of data distribution was checked using Anderson–Darling and Kolmogorov–Smirnov tests. Dunnett’s multiple comparison test and Friedman test were used to compare variables, when appropriate. A p-value lower than 0.05 (two-sided) was considered to be statistically significant.

3. Results

After treatment with benralizumab, all patients reported a considerable reduction of asthma exacerbation rate. When compared to baseline, during biological therapy with benralizumab the number of exacerbations recorded in the previous year decreased from 8.00 ± 3.00 to 0.85 ± 1.53 (p < 0.0001) (Figure 1). The decrement of asthma exacerbation frequency due to benralizumab resulted to be statistically significant also in comparison to the pre-shift period (after treatment with omalizumab), when the mean number of exacerbations was 4.60 ± 3.10 (p < 0.01) (Figure 1). This result was paralleled by the reduction of the hospitalization rate, which decreased from the baseline value of 0.75 ± 0.71/year to 0.15 ± 0.36/year (p < 0.01) after treatment with omalizumab (pre-shift period), and zeroed after at least one year of add-on therapy with benralizumab (p < 0.001) (Figure 2). The mean number of daily SABA inhalations, used as needed rescue medications, was 0.10 ± 0.44 after therapy with benralizumab; this value was considerably lower than those detected at baseline (2.60 ± 1.69; p < 0.0001), and after add-on treatment with omalizumab (1.95 ± 1.82; p < 0.001), respectively (Figure 3). It was also possible to drastically reduce OCS intake, through a progressive lowering of OCS median dosage from baseline 11.25 mg (5.00–25.00) down to 5.00 mg (0.00–12.50; not significant) after at least 12 months of add-on therapy with omalizumab, and to 0.00 mg (0.00–0.00) (p < 0.001) after at least 12 months of add-on therapy with benralizumab, respectively (Figure 4). In particular, at baseline, 17 patients (85%) were on regular OCS treatment, who decreased to 14 (70%) after omalizumab therapy, and to 4 (20%) after benralizumab treatment, respectively.
The median ACT score increased from 12.00 (7.00–15.00) at baseline to 20.00 (17.25–23.75) during treatment with benralizumab (p < 0.0001) (Figure 5). A significant rise of ACT score was experienced also when comparing post-benralizumab assessment to the result obtained before switching biological therapy, characterized by a median score of 15.00 (12.25–17.00) (p < 0.05). Moreover, in 9 patients also complaining of CRSwNP, the SNOT-22 score decreased from the mean baseline value of 58.44 ± 17.87 to 53.89 ± 15.93 after omalizumab treatment (p < 0.05), and to 43.44 ± 19.91 after benralizumab therapy (p < 0.01), respectively (Figure 6). We also detected a significant difference (p < 0.05) between the two SNOT-22 scores calculated after treatments with omalizumab and benralizumab, respectively (Figure 6).
The mean pre-bronchodilator FEV1 enhanced from the baseline measurement of 1.71 ± 0.46 L at baseline to 2.18 ± 0.63 L after benralizumab therapy (p < 0.01). Mean pre-bronchodilator FEV1 also significantly increased with respect to pre-shift (post-omalizumab) assessment, characterized by a mean value of 1.81 ± 0.48 L (p < 0.05) (Figure 7). Finally, in addition to inducing the above clinical and functional effects, after at least 12 months of therapy benralizumab also zeroed the median blood eosinophil level, thus lowering it from the baseline count of 543.5 (360.0–1048) to 0.00 cells/μL (0.00–0.00) (p < 0.0001). The decrease of median blood eosinophil number was statistically significant even with respect to the time point of pre-switching biological therapy (p < 0.0001), corresponding to the end of treatment with omalizumab (Figure 8).

4. Discussion

The recent advances in the rapidly evolving scenario of the biological treatment of severe asthma have provided, during the last few years, an increasing number of valuable therapeutic options. Such a relevant progress makes it possible, in many cases, to tailor the biological therapy on the basis of the specific sub-phenotype expressed by each patient with severe type 2 asthma [20,23,55]. A careful phenotypic characterization relies on the combined clinical and functional evaluation, necessarily integrated by the measurement of useful biomarkers of type 2 asthma (serum IgE levels, blood eosinophil count, FeNO) [56]. The phenotype-driven first choice of a given biologic is often associated with a satisfactory therapeutic response. However, some patients with severe asthma do not achieve a sufficient control of their disease during the initial biological treatment, thus requiring a therapeutic shift [57]. This is especially true for patients treated with omalizumab, which has been for a long time the only approved anti-asthma monoclonal antibody [26]. Indeed, several studies have shown that allergic patients with severe asthma, who are not responsive to omalizumab, can be successfully switched to mepolizumab [34,35,36,37,38]. Nevertheless, to our knowledge scientific literature lacks publications referring to an eventual therapeutic shift from omalizumab to benralizumab. In regard to allergic patients with severe asthma previously uncontrolled by anti-IgE therapy, the present multi-center real-life experience clearly suggests that switching from omalizumab to benralizumab can induce significant improvements related to important clinical, functional, and biological aspects. This can be especially true for our severe asthmatic patients, who were characterized by a late-onset asthma, thus being more likely exposed to the risk of a poor response to omalizumab. In fact, real-life investigations have shown that the therapeutic response to omalizumab progressively decreases as age increases [58].
In particular, benralizumab significantly decreased the annual number of asthma exacerbations not only in comparison to baseline, but especially with respect to the effects of omalizumab, whose therapeutic action was quite modest thus not allowing a clinically relevant prevention of exacerbations, which was subsequently achieved after switching to benralizumab. Differently from omalizumab, benralizumab was indeed able to reduce asthma exacerbations much more than 50%, which is the threshold suggested by the British National Institute for Health and Care Excellence (NICE) as a reliable clinical goal to be pursued by anti-asthma therapies [59]. This impressive therapeutic effect of benralizumab is likely dependent on its anti-eosinophil activity, capable of zeroing blood eosinophil number, which on the contrary was not affected by omalizumab. In fact, a blood eosinophil count superior to 300–400 cells/μL is associated with a high risk of asthma exacerbations [60,61], and our patients had a median baseline value of blood eosinophils which was greater than 500 cells/μL. Hence, our results further corroborate the evidence that maintaining blood eosinophils at a low level decreases the risk of asthma exacerbations [62]. It can thus be argued that in some allergic patients with severe eosinophilic asthma like ours, the pharmacologic blockade of IgE is not sufficient to dramatically reduce disease exacerbations. Evidently, in such subjects the powerful IL-5R antagonism and the associated ADCC mechanism sustained by benralizumab are much more advantageous than anti-IgE therapy in providing an effective decrease in blood eosinophil count, and the consequent prevention of asthma exacerbations. Moreover, when compared to omalizumab treatment, the more effective benralizumab-induced decrement of asthma exacerbations made it possible for patients shifted to this drug to suppress their needs for hospitalization and OCS intake.
With respect to omalizumab treatment and in addition to the positive impact on the annual asthma exacerbation rate, benralizumab also elicited other clinical improvements, especially regarding symptom control. Indeed, our patients were characterized by a poor control of asthma symptoms, expressed by a quite low baseline ACT score, which modestly and not significantly enhanced after omalizumab treatment, whereas benralizumab induced an increase which resulted to be significant not only with respect to baseline, but also versus omalizumab therapy. In particular, after switching from omalizumab to benralizumab, our patients reached the crucial ACT score of 20, which reflects an adequate asthma control [63]. In real-life experiences like ours ACT is highly reliable as well as more practicable and easier to be performed when compared to asthma control questionnaires (ACQ), mostly used in RCT [64]. By remarkably improving the overall asthma control, benralizumab allowed a drastic reduction of SABA daily inhalations, utilized as rescue medication. Again, benralizumab significantly decreased SABA consumption not only with respect to baseline, but also in comparison to the slight and not significant effect produced by omalizumab. In addition to ameliorating asthma symptoms, benralizumab also improved the subjective symptoms related to upper airway diseases, as shown by the reduction of SNOT-22 score reported by our patients with severe asthma and nasal polyposis. The SNOT-22 score was further lowered by benralizumab when compared with the significant therapeutic action of omalizumab. These results are not very surprising, in consideration of recent similar data emerging from both RCT and real-world investigations, showing that both omalizumab and benralizumab are effective in improving the symptoms of nasal polyposis [48,49,65,66,67]. On the other hand, severe eosinophilic atopic asthma and allergic CRSwNP share common pathogenic mechanisms including the key roles played by IgE and IL-5-dependent airway eosinophilia [18,68,69]. Our patients with severe asthma and nasal polyposis responded very well to benralizumab, not differently than those without nasal polyps.
In regard to lung function, at baseline our patients were characterized by a relevant airflow limitation (mean pre-bronchodilator FEV1: 62% pred). The initial treatment with omalizumab induced a scanty and not significant FEV1 change, which was overwhelmed by the subsequent therapy with benralizumab, responsible for a significant FEV1 increase amounting after 1 year to more than 400 mL with respect to baseline, and to more than 300 mL when compared to the end of omalizumab treatment (pre-switching), respectively. Such a remarkable improvement of bronchial obstruction, provided by benralizumab, is probably due to the powerful anti-eosinophil activity of this drug. Although the relationship between blood and sputum eosinophil levels is still debated, and with regard to this context there is disagreement in scientific literature, a recent reliable study has clearly shown that blood eosinophils are an excellent predictor of sputum eosinophilia in patients with uncontrolled asthma [70]. Therefore, because blood eosinophil numbers reflect the entity of airway eosinophilia, it is likely that eosinophilic inflammation leads to the development of airflow limitation. This pathogenic circuit can thus be effectively interrupted by benralizumab, but not by omalizumab, which in our patients did not affect at all the level of blood eosinophils.
Taken together, the results of the present real-life study strongly suggest that a subset of allergic patients with severe eosinophilic asthma, unresponsive to an initial add-on treatment with omalizumab, can greatly benefit from a subsequent biological therapy with benralizumab. This therapeutic shift was allowed by the phenotypic features of our patients, belonging to a group of subjects who express high levels of multiple biomarkers of type 2 asthma, including serum IgE and blood eosinophils [71]. Of course, the primary goal of clinicians managing severe asthma should be to initially pursue the best possible therapeutic choice for their patients. However, when some asthmatic patients experience residual symptoms and exacerbations despite their first access to a phenotype-based biological therapy, physicians must investigate eventual alternative approaches. This is particularly true in regard to the frequent overlap between allergic and eosinophilic traits, which often shapes a multidimensional eligibility of severe asthmatic patients to anti-IgE treatment, as well as to anti-IL-5, anti-IL-5 receptor, and anti-IL-4/IL-13 receptor therapies [72,73]. Within such a context, blood eosinophil counts can play an important predictive role. Indeed, high blood eosinophil numbers, but not serum IgE levels, are associated with a high risk of asthma exacerbations in patients with severe, uncontrolled disease [74]. These considerations can help to explain our current data referring to allergic patients with severe eosinophilic asthma switched from omalizumab to benralizumab, which has been shown to be very effective in such subjects independently of serum IgE concentrations [74]. Whilst elevated blood eosinophil counts are predictive of benralizumab efficacy, serum IgE levels do not predict the response to omalizumab [74,75]. Hence, a plausible reading key for our results, obtained in asthmatic patients with quite elevated blood eosinophil numbers, may imply that omalizumab-resistant eosinophilic inflammation can be adequately controlled by benralizumab. It can thus be hypothesized that in our allergic patients the main pathobiologic mechanism, underlying severe eosinophilic asthma, originated from an excessive local and systemic production of IL-5, responsible for high counts of eosinophils in both airways and blood. This IL-5-dependent eosinophilic inflammation can be suppressed by benralizumab, but not by omalizumab. Such a speculation could be extended to both upper and lower airways for our patients complaining of severe eosinophilic asthma and nasal polyposis, highly susceptible to the add-on biological therapy with benralizumab [48,49,65,66]. Among the comorbidities of severe asthma, nasal polyposis is indeed one of the most reliable predictors of an effective therapeutic response to benralizumab [76].
Of course, omalizumab remains the first drug selection for uncontrolled atopic asthmatics [14,20], whose clinical history is clearly characterized by a pivotal role played by allergic sensitization. Based on this consideration, we initially chose omalizumab as add-on biological therapy for our patients with severe atopic asthma, being convinced that IgE-mediated allergic pathways were the main mechanisms responsible for both clinical and functional features. However, in such subjects a close attention should also be paid to blood eosinophil count. Indeed, in case of the eventual concomitance of a relevant blood eosinophilia, the therapeutic orientation could deviate from omalizumab towards mepolizumab, reslizumab, or benralizumab. Anyway, if a phenotypic-driven prescription of omalizumab does not yield satisfactory clinical results within a year of treatment, a theapeutic switch to another biologic should be considered.
In conclusion, we think that the main strength of our real-life experience is based on the demonstration of the effectiveness of the pharmacologic shift from omalizumab to benralizumab, detected in allergic patients with severe eosinophilic asthma. These results are very interesting, because the effects of the above therapeutic switching are largely unexplored in atopic subjects with difficult-to-treat type 2 asthma. On the other hand, similar to other real-world investigations, our present study has some limitations including the relatively low number of enrolled patients, as well as the lack of randomization and placebo control.

Author Contributions

All authors contributed to data analysis, drafting, or revising the paper, agreed to submit the manuscript to this journal, gave the final approval for the submitted version, and agreed to be accountable for all aspects of the work. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Institutional Review Board Statement

This study was carried out in agreement to what decided by the local Ethical Committee of Calabria Region (Catanzaro, Italy; document n. 257—15 July 2021).

Informed Consent Statement

Written informed consent to publish this paper has been obtained from all subjects involved in the study.

Data Availability Statement

The data presented in this study are available on request from the corresponding author.

Conflicts of Interest

The authors declare that there is no conflict of interest.

References

  1. Wenzel, S.E. Severe Adult Asthmas: Integrating Clinical Features, Biology, and Therapeutics to Improve Outcomes. Am. J. Respir. Crit. Care Med. 2021, 203, 809–821. [Google Scholar] [CrossRef] [PubMed]
  2. Camiolo, M.J.; Kale, S.L.; Oriss, T.B.; Gauthier, M.; Ray, A. Immune responses and exacerbations in severe asthma. Curr. Opin. Immunol. 2021, 72, 34–42. [Google Scholar] [CrossRef]
  3. McDowell, P.J.; Heaney, L.G. Different endotypes and phenotypes drive the heterogeneity in severe asthma. Allergy 2019, 75, 302–310. [Google Scholar] [CrossRef] [Green Version]
  4. Matucci, A.; Bormioli, S.; Nencini, F.; Maggi, E.; Vultaggio, A. The emerging role of type 2 inflammation in asthma. Expert Rev. Clin. Immunol. 2020, 17, 63–71. [Google Scholar] [CrossRef]
  5. Hammad, H.; Lambrecht, B.N. The basic immunology of asthma. Cell 2021, 184, 1469–1485. [Google Scholar] [CrossRef]
  6. Carr, T.F.; Zeki, A.A.; Kraft, M. Eosinophilic and Noneosinophilic Asthma. Am. J. Respir. Crit. Care Med. 2018, 197, 22–37. [Google Scholar] [CrossRef]
  7. Nelson, R.K.; Bush, A.; Stokes, J. Eosinophilic asthma. J. Allergy Clin. Immunol Pract. 2020, 8, 465–473. [Google Scholar] [CrossRef]
  8. Tran, T.N.; Zeiger, R.; Peters, S.P.; Colice, G.; Newbold, P.; Goldman, M.; Chipps, B.E. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann. Allergy Asthma Immunol. 2016, 116, 37–42. [Google Scholar] [CrossRef] [PubMed]
  9. Rossios, C.; Pavlidis, S.; Hoda, U.; Kuo, C.-H.; Wiegman, C.; Russell, K.; Sun, K.; Loza, M.J.; Baribaud, F.; Durham, A.L.; et al. Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma. J. Allergy Clin. Immunol. 2017, 141, 560–570. [Google Scholar] [CrossRef] [Green Version]
  10. Schleich, F.; Brusselle, G.; Louis, R.; Vandenplas, O.; Michils, A.; Pilette, C.; Peche, R.; Manise, M.; Joos, G. Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR). Respir. Med. 2014, 108, 1723–1732. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  11. Kuruvilla, M.E.; Lee, F.E.-H.; Lee, G.B. Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease. Clin. Rev. Allergy Immunol. 2018, 56, 219–233. [Google Scholar] [CrossRef] [PubMed]
  12. Rodriguez-Rodriguez, N.; Gogoi, M.; McKenzie, A.N. Group 2 Innate Lymphoid Cells: Team Players in Regulating Asthma. Annu. Rev. Immunol. 2021, 39, 167–198. [Google Scholar] [CrossRef]
  13. Maggi, L.; Montaini, G.; Mazzoni, A.; Rossettini, B.; Capone, M.; Rossi, M.C.; Santarlasci, V.; Liotta, F.; Rossi, O.; Gallo, O.; et al. Human circulating group 2 innate lymphoid cells can express CD154 and promote IgE production. J. Allergy Clin. Immunol. 2017, 139, 964–976.e4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  14. Froidure, A.; Mouthuy, J.; Durham, S.R.; Chanez, P.; Sibille, Y.; Pilette, C. Asthma phenotypes and IgE responses. Eur. Respir. J. 2016, 47, 304–319. [Google Scholar] [CrossRef] [Green Version]
  15. Lambrecht, B.N.; Hammad, H.; Fahy, J.V. The cytokines of asthma. Immunity 2019, 50, 975–991. [Google Scholar] [CrossRef]
  16. Gour, N.; Wills-Karp, M. IL-4 and IL-13 in allergic airway disease. Cytokine 2015, 75, 68–78. [Google Scholar] [CrossRef] [Green Version]
  17. Ricciardolo, F.L.M.; Silkoff, P.E. Perspectives on exhaled nitric oxide. J. Breath Res. 2017, 11, 047104. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  18. Pelaia, C.; Paoletti, G.; Puggioni, F.; Racca, F.; Pelaia, G.; Canonica, G.W.; Heffler, E. Interleukin-5 in the Pathophysiology of Severe Asthma. Front. Physiol. 2019, 10, 1514. [Google Scholar] [CrossRef] [PubMed]
  19. GINA. Global Strategy for Asthma Management and Prevention 2021. Available online: www.ginasthma.org (accessed on 25 August 2021).
  20. Bousquet, J.; Brusselle, G.; Buhl, R.; Busse, W.W.; Cruz, A.A.; Djukanovic, R.; Domingo, C.; Hanania, N.A.; Humbert, M.; Gow, A.M.; et al. Care pathways for the selection of a biologic in severe asthma. Eur. Respir. J. 2017, 50, 1701782. [Google Scholar] [CrossRef] [Green Version]
  21. Bakakos, A.; Loukides, S.; Usmani, O.S.; Bakakos, P. Biologics in severe asthma: The overlap endotype—Opportunities and challenges. Expert Opin. Biol. Ther. 2020, 20, 1427–1434. [Google Scholar] [CrossRef] [PubMed]
  22. Wenzel, S. Severe asthma: From characteristics to phenotypes to endotypes. Clin. Exp. Allergy 2012, 42, 650–658. [Google Scholar] [CrossRef] [PubMed]
  23. Suraya, R.; Nagano, T.; Katsurada, M.; Sekiya, R.; Kobayashi, K.; Nishimura, Y. Molecular mechanism of asthma and its novel molecular target therapeutic agent. Respir. Investig. 2021, 59, 291–301. [Google Scholar] [CrossRef]
  24. Albers, F.C.; Müllerová, H.; Gunsoy, N.B.; Shin, J.-Y.; Nelsen, L.M.; Bradford, E.S.; Cockle, S.M.; Suruki, R.Y. Biologic treatment eligibility for real-world patients with severe asthma: The IDEAL study. J. Asthma 2017, 55, 152–160. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  25. Pelaia, G.; Canonica, G.W.; Matucci, A.; Paolini, R.; Triggiani, M.; Paggiaro, P. Targeted therapy in severe asthma today: Focus on immunoglobulin E. Drug Des. Dev. Ther. 2017, ume 11, 1979–1987. [Google Scholar] [CrossRef] [Green Version]
  26. Pelaia, C.; Calabrese, C.; Terracciano, R.; De Blasio, F.; Vatrella, A.; Pelaia, G. Omalizumab, the first available antibody for biological treatment of severe asthma: More than a decade of real-life effectiveness. Ther. Adv. Respir. Dis. 2018, 12. [Google Scholar] [CrossRef] [Green Version]
  27. Rodrigo, G.J.; Neffen, H.; Castro-Rodriguez, J.A. Efficacy and safety of subcutaneous omalizumab vs placebo as add-on therapy to corticosteroids for children and adults with asthma: A systematic review. Chest 2011, 139, 28–35. [Google Scholar] [CrossRef] [Green Version]
  28. Cabrejos, S.; Moreira, A.; Ramirez, A.; Quirce, S.; Campos, G.S.; Dávila, I.; Campo, P. FENOMA Study: Achieving Full Control in Patients with Severe Allergic Asthma. J. Asthma Allergy 2020, 13, 159–166. [Google Scholar] [CrossRef] [PubMed]
  29. Pelaia, G.; Gallelli, L.; Romeo, P.; Renda, T.; Busceti, M.; Proietto, A.; Grembiale, R.; Marsico, S.; Maselli, R.; Vatrella, A. Omalizumab decreases exacerbation frequency, oral intake of corticosteroids and peripheral blood eosinophils in atopic patients with uncontrolled asthma. Int. J. Clin. Pharmacol. Ther. 2011, 49, 713–721. [Google Scholar] [CrossRef]
  30. Pelaia, C.; Calabrese, C.; Barbuto, S.; Busceti, M.T.; Preianò, M.; Gallelli, L.; Savino, R.; Vatrella, A.; Pelaia, G. Omalizumab lowers asthma exacerbations, oral cor-ticosteroid intake and blood eosinophils: Results of a 5-year single centre observational study. Pulm. Pharmacol. Ther. 2019, 54, 25–30. [Google Scholar] [CrossRef]
  31. Pace, E.; Ferraro, M.; Bruno, A.; Chiappara, G.; Bousquet, J.; Gjomarkaj, M. Clinical Benefits of 7 Years of Treatment with Omalizumab in Severe Uncontrolled Asthmatics. J. Asthma 2011, 48, 387–392. [Google Scholar] [CrossRef]
  32. Menzella, F.; Galeone, C.; Formisano, D.; Castagnetti, C.; Ruggiero, P.; Simonazzi, A.; Zucchi, L. Real-life Efficacy of Omalizumab After 9 Years of Follow-up. Allergy Asthma Immunol. Res. 2017, 9, 368–372. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  33. Leru, P.M.; Anton, V.F. Real-Life Benefit of Omalizumab in Improving Control of Bronchial Asthma During COVID-19 Pandemic. Cureus 2021, 1. [Google Scholar] [CrossRef] [PubMed]
  34. Chapman, K.R.; Albers, F.C.; Chipps, B.; Muñoz, X.; Devouassoux, G.; Bergna, M.; Galkin, D.; Azmi, J.; Mouneimne, D.; Price, R.G.; et al. The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma. Allergy 2019, 74, 1716–1726. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  35. Carpagnano, G.E.; Pelaia, C.; D’Amato, M.; Crimi, N.; Scichilone, N.; Scioscia, G.; Resta, O.; Calabrese, C.; Pelaia, G.; Quarato, C.M.I.; et al. Switching from omalizumab to mepolizumab: Real-life experience from Southern Italy. Ther. Adv. Respir. Dis. 2020, 14. [Google Scholar] [CrossRef]
  36. Carpagnano, G.E.; Resta, E.; Povero, M.; Pelaia, C.; D’Amato, M.; Crimi, N.; Scichilone, N.; Scioscia, G.; Resta, O.; Calabrese, C.; et al. Clinical and economic consequences of switching from omalizumab to mepolizumab in uncontrolled severe eosinophilic asthma. Sci. Rep. 2021, 11, 8. [Google Scholar] [CrossRef]
  37. Bagnasco, D.; Menzella, F.; Caminati, M.; Caruso, C.; Guida, G.; Bonavia, M.; Riccio, A.; Milanese, M.; Manfredi, A.; Senna, G.; et al. Efficacy of mepolizumab in patients with previous omalizumab treatment failure: Real-life observation. Allergy 2019, 74, 2539–2541. [Google Scholar] [CrossRef] [PubMed]
  38. Liu, M.C.; Chipps, B.; Munoz, X.; Devouassoux, G.; Bergna, M.; Smith, S.G.; Price, R.G.; Galkin, D.V.; Azmi, J.; Mouneimne, D.; et al. Benefit of switching to mepolizumab from omalizumab in severe eosinophilic asthma based on patient characteristics. Respir. Res. 2021, 22, 1–13. [Google Scholar] [CrossRef]
  39. Pelaia, C.; Vatrella, A.; Busceti, M.T.; Gallelli, L.; Terracciano, R.; Savino, R.; Pelaia, G. Severe eosinophilic asthma: From the pathogenic role of interleukin-5 to the therapeutic action of mepolizumab. Drug Des. Dev. Ther. 2017, 11, 3137–3144. [Google Scholar] [CrossRef] [Green Version]
  40. Pelaia, C.; Busceti, M.T.; Solinas, S.; Terracciano, R.; Pelaia, G. Real-life evaluation of the clinical, functional, and hematological effects of mepolizumab in patients with severe eosinophilic asthma: Results of a single-centre observational study. Pulm. Pharmacol. Ther. 2018, 53, 1–5. [Google Scholar] [CrossRef]
  41. Bagnasco, D.; Milanese, M.; Rolla, G.; Lombardi, C.; Bucca, C.; Heffler, E.; Canonica, G.W.; Passalacqua, G. The North-Western Italian experience with anti IL-5 therapy amd comparison with regulatory trials. World Allergy Organ. J. 2018, 11, 34. [Google Scholar] [CrossRef] [Green Version]
  42. Pelaia, C.; Crimi, C.; Pelaia, G.; Nolasco, S.; Campisi, R.; Heffler, E.; Valenti, G.; Crimi, N. Real-life evaluation of mepolizumab efficacy in patients with severe eosinophilic asthma, according to atopic trait and allergic phenotype. Clin. Exp. Allergy 2020, 50, 780–788. [Google Scholar] [CrossRef] [PubMed]
  43. Pelaia, C.; Crimi, C.; Vatrella, A.; Tinello, C.; Terracciano, R.; Pelaia, G. Molecular Targets for Biological Therapies of Severe Asthma. Front. Immunol. 2020, 11. [Google Scholar] [CrossRef] [PubMed]
  44. Pelaia, C.; Calabrese, C.; Vatrella, A.; Busceti, M.T.; Garofalo, E.; Lombardo, N.; Terracciano, R.; Pelaia, G. Benralizumab: From the Basic Mechanism of Action to the Potential Use in the Biological Therapy of Severe Eosinophilic Asthma. BioMed Res. Int. 2018, 2018, 1–9. [Google Scholar] [CrossRef]
  45. Pelaia, C.; Vatrella, A.; Bruni, A.; Terracciano, R.; Pelaia, G. Benralizumab in the treatment of severe asthma: Design, development and potential place in therapy. Drug Des. Dev. Ther. 2018, ume 12, 619–628. [Google Scholar] [CrossRef] [Green Version]
  46. Pelaia, C.; Busceti, M.T.; Vatrella, A.; Rago, G.F.; Crimi, C.; Terracciano, R.; Pelaia, G. Real-life rapidity of benralizumab effects in patients with severe allergic asthma: Assessment of blood eosinophils, symptom control, lung function and oral corticosteroid intake after the first drug dose. Pulm. Pharmacol. Ther. 2019, 58, 101830. [Google Scholar] [CrossRef]
  47. Pelaia, C.; Busceti, M.T.; Crimi, C.; Carpagnano, G.E.; Lombardo, N.; Terracciano, R.; Vatrella, A.; Pelaia, G. Real-Life effects of benralizumab on exacerbation number and lung hyperinflation in atopic patients with severe eosinophilic asthma. Biomed. Pharmacother. 2020, 129, 110444. [Google Scholar] [CrossRef] [PubMed]
  48. Pelaia, C.; Busceti, M.T.; Vatrella, A.; Ciriolo, M.; Garofalo, E.; Crimi, C.; Terracciano, R.; Lombardo, N.; Pelaia, G. Effects of the first three doses of benralizumab on symptom control, lung function, blood eosinophils, oral corticosteroid intake, and nasal polyps in a patient with severe allergic asthma. SAGE Open Med. Case Rep. 2020, 8. [Google Scholar] [CrossRef] [PubMed]
  49. Lombardo, N.; Pelaia, C.; Ciriolo, M.; Della Corte, M.; Piazzetta, G.; LoBello, N.; Viola, P.; Pelaia, G. Real-life effects of benralizumab on allergic chronic rhinosinusitis and nasal polyposis associated with severe asthma. Int. J. Immunopathol. Pharmacol. 2020, 34. [Google Scholar] [CrossRef] [PubMed]
  50. Kavanagh, J.E.; Hearn, A.P.; Dhariwal, J.; D’Ancona, G.; Douiri, A.; Roxas, C.; Fernandes, M.; Green, L.; Thomson, L.; Nanzer, A.M.; et al. Real-World Effectiveness of Benralizumab in Severe Eosinophilic Asthma. Chest 2020, 159, 496–506. [Google Scholar] [CrossRef]
  51. Pelaia, C.; Crimi, C.; Benfante, A.; Caiaffa, M.F.; Calabrese, C.; Carpagnano, G.E.; Ciotta, D.; D’Amato, M.; Macchia, L.; Nolasco, S.; et al. Therapeutic Effects of Benralizumab Assessed in Patients with Severe Eosinophilic Asthma: Real-Life Evaluation Correlated with Allergic and Non-Allergic Phenotype Expression. J. Asthma Allergy 2021, 14, 163–173. [Google Scholar] [CrossRef]
  52. Chung, K.F.; Wenzel, S.E.; Brozek, J.L.; Bush, A.; Castro, M.; Sterk, P.J.; Adcock, I.M.; Bateman, E.D.; Bel, E.H.; Bleecker, E.R.; et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur. Respir. J. 2013, 43, 343–373. [Google Scholar] [CrossRef] [Green Version]
  53. Menzella, F.; Facciolongo, N.; Castagnetti, C.; Simonazzi, A.; Zucchi, L. Omalizumab: When the non-responder is a late-responder. Eur. Ann. Allergy Clin. Immunol. 2009, 41. [Google Scholar]
  54. Graham, B.L.; Steenbruggen, I.; Miller, M.R.; Barjaktarevic, I.Z.; Cooper, B.G.; Hall, G.L.; Hallstrand, T.S.; Kaminsky, D.A.; McCarthy, K.; McCormack, M.C.; et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am. J. Respir. Crit. Care Med. 2019, 200, e70–e88. [Google Scholar] [CrossRef]
  55. Pelaia, C.; Pelaia, G.; Crimi, C. Biologics in severe asthma. Minerva Med. 2021. Online ahead of print. [Google Scholar] [CrossRef]
  56. Ricciardolo, F.L.; Bertolini, F.; Carriero, V.; Sprio, A.E. Asthma phenotypes and endotypes. Minerva Med. 2021, 112. [Google Scholar] [CrossRef]
  57. Numata, T.; Araya, J.; Miyagawa, H.; Okuda, K.; Fujita, Y.; Utsumi, H.; Takekoshi, D.; Hashimoto, M.; Minagawa, S.; Ishikawa, T.; et al. Effectiveness of Switching Biologics for Severe Asthma Patients in Japan: A Single-Center Retrospective Study. J. Asthma Allergy 2021, 14, 609–618. [Google Scholar] [CrossRef] [PubMed]
  58. Sposato, B.; Scalese, M.; Latorre, M.; Scichilone, N.; Matucci, A.; Milanese, M.; Masieri, S.; Rolla, G.; Steinhilber, G.; Rosati, Y.; et al. Effects of omalizumab in severe asthmatics across ages: A real life Italian experience. Respir. Med. 2016, 119, 141–149. [Google Scholar] [CrossRef] [Green Version]
  59. Drick, N.; Seeliger, B.; Welte, T.; Fuge, J.; Suhling, H. Anti-IL-5 therapy in patients with severe eosinophilic asthma—Clinical efficacy and possible criteria for treatment response. BMC Pulm. Med. 2018, 18, 1–9. [Google Scholar] [CrossRef]
  60. Price, D.B.; Rigazio, A.; Campbell, J.D.; Bleecker, E.R.; Corrigan, C.; Thomas, M.; Wenzel, S.; Wilson, A.M.; Small, M.B.; Gopalan, G.; et al. Blood eosinophil count and prospective annual asthma disease burden: A UK cohort study. Lancet Respir. Med. 2015, 3, 849–858. [Google Scholar] [CrossRef]
  61. Zeiger, R.S.; Schatz, M.; Li, Q.; Chen, W.; Khatry, D.; Gossage, D.; Tran, T.N. High Blood Eosinophil Count Is a Risk Factor for Future Asthma Exacerbations in Adult Persistent Asthma. J. Allergy Clin. Immunol. 2014, 2, 741–750.e4. [Google Scholar] [CrossRef]
  62. Zeiger, R.S.; Schatz, M.; Dalal, A.A.; Chen, W.; Sadikova, E.; Suruki, R.Y.; Kawatkar, A.A.; Qian, L. Blood Eosinophil Count and Outcomes in Severe Uncontrolled Asthma: A Prospective Study. J. Allergy Clin. Immunol. 2017, 5, 144–153.e8. [Google Scholar] [CrossRef]
  63. Nathan, R.A.; Sorkness, C.A.; Kosinski, M.; Schatz, M.; Li, J.T.; Marcus, P.; Murray, J.J.; Pendergraft, T.B. Development of the asthma control test: A survey for assessing asthma control. J. Allergy Clin. Immunol. 2004, 113, 59–65. [Google Scholar] [CrossRef]
  64. Jia, C.E.; Zhang, H.P.; Lv, Y.; Liang, R.; Jiang, Y.Q.; Powell, H.; Fu, J.-J.; Wang, L.; Gibson, P.; Wang, G. The Asthma Control Test and Asthma Control Questionnaire for assessing asthma control: Systematic review and meta-analysis. J. Allergy Clin. Immunol. 2013, 131, 695–703. [Google Scholar] [CrossRef]
  65. Harrison, T.W.; Chanez, P.; Menzella, F.; Canonica, G.W.; Louis, R.; Cosio, B.G.; Lugogo, N.L.; Mohan, A.; Burden, A.; McDermott, L.; et al. Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): A randomized, controlled, phase 3b trial. Lancet Respir Med. 2021, 9, 260–274. [Google Scholar] [CrossRef]
  66. Nolasco, S.; Crimi, C.; Pelaia, C.; Benfante, A.; Caiaffa, M.F.; Calabrese, C.; Carpagnano, G.E.; Ciotta, D.; D’Amato, M.; Macchia, L.; et al. Benralizumab effectiveness in severe eosinophilic asthma patients with and without chronic rhinosinusitis with nasal polyps: A real-world multicentre study. J. Allergy Clin. Immunol Pract. 2021. Online ahead of print 19:S2213-2198(21)00903-X. [Google Scholar] [CrossRef]
  67. Gevaert, P.; Omachi, T.A.; Corren, J.; Mullol, J.; Han, J.; Lee, S.E.; Kaufman, D.; Ligueros-Saylan, M.; Howard, M.; Zhu, R.; et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J. Allergy Clin. Immunol. 2020, 146, 595–605. [Google Scholar] [CrossRef] [PubMed]
  68. Matucci, A.; Bormioli, S.; Nencini, F.; Chiccoli, F.; Vivarelli, E.; Maggi, E.; Vultaggio, A. Asthma and chronic rhinosinusitis: How similar are they in pathogenesis and treatment responses? Int. J. Mol. Sci. 2021, 22, 3340. [Google Scholar] [CrossRef] [PubMed]
  69. Scadding, G.K.; Scadding, G.W. Innate and adaptive immunity: ILC2 and Th2 cells in upper and lower airway allergic diseases. J. Allergy Clin. Immunol Pract. 2021, 9, 1851–1857. [Google Scholar] [CrossRef] [PubMed]
  70. Gao, J.; Wu, F. Association between fractional exhaled nitric oxide, sputum induction and peripheral blood eosinophil in un-controlled asthma. Allergy Asthma Clin. Immunol. 2018, 14, 21. [Google Scholar] [CrossRef] [Green Version]
  71. Han, Y.Y.; Zhang, X.; Wang, J.; Wang, G.; Oliver, B.G.; Zhang, H.P.; Kang, D.Y.; Wang, L.; Qiu, Z.X.; Li, W.M. Multidimensional Assessment of Asthma Identifies Clinically Relevant Phenotype Overlap: A Cross-Sectional Study. J. Allergy Clin. Immunol. 2020, 9, 349–362.e18. [Google Scholar] [CrossRef]
  72. Lacwik, P.; Kupczyk, M. Asthma Phenotype Overlap: More May Be Less. J. Allergy Clin. Immunol. 2021, 9, 363–364. [Google Scholar] [CrossRef] [PubMed]
  73. Zervas, E.; Samitas, K.; Papaioannou, A.I.; Bakakos, P.; Loukides, S.; Gaga, M. An algorithmic approach for the treatment of severe uncontrolled asthma. ERJ Open Res. 2018, 4, 00125–2017. [Google Scholar] [CrossRef] [PubMed]
  74. Jackson, D.J.; Humbert, M.; Hirsch, I.; Newbold, P.; Gil, E.G. Ability of serum IgE concentration to predict exacerbation risk and benralizumab ef-ficacy for patients with severe eosinophilic asthma. Adv. Ther. 2020, 37, 718–729. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  75. Wahn, U.; Martin, C.; Freeman, P.; Blogg, M.; Jimenez, P. Relationship between pretreatment specific IgE and the response to omalizumab therapy. Allergy 2009, 64, 1780–1787. [Google Scholar] [CrossRef]
  76. Bleecker, E.R.; Wechsler, M.E.; Fitzgerald, J.M.; Menzies-Gow, A.; Wu, Y.; Hirsch, I.; Goldman, M.; Newbold, P.; Zangrilli, J.G. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur. Respir. J. 2018, 52, 1800936. [Google Scholar] [CrossRef] [Green Version]
Biomedicines 09 01822 g001 550
Figure 1. Effects of omalizumab and benralizumab on the annual number of asthma exacerbations. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. ** p < 0.01; **** p < 0.0001.
Figure 1. Effects of omalizumab and benralizumab on the annual number of asthma exacerbations. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. ** p < 0.01; **** p < 0.0001.
Biomedicines 09 01822 g001
Biomedicines 09 01822 g002 550
Figure 2. Effects of omalizumab and benralizumab on the annual number of hospitalizations for asthma exacerbations. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. ** p < 0.01; *** p < 0.001. ns: not significant.
Figure 2. Effects of omalizumab and benralizumab on the annual number of hospitalizations for asthma exacerbations. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. ** p < 0.01; *** p < 0.001. ns: not significant.
Biomedicines 09 01822 g002
Biomedicines 09 01822 g003 550
Figure 3. Effects of omalizumab and benralizumab on the daily number of SABA inhalations. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. *** p < 0.001; **** p < 0.0001. ns: not significant.
Figure 3. Effects of omalizumab and benralizumab on the daily number of SABA inhalations. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. *** p < 0.001; **** p < 0.0001. ns: not significant.
Biomedicines 09 01822 g003
Biomedicines 09 01822 g004 550
Figure 4. Effects of omalizumab and benralizumab on the daily prednisone intake. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. *** p < 0.001. ns: not significant.
Figure 4. Effects of omalizumab and benralizumab on the daily prednisone intake. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. *** p < 0.001. ns: not significant.
Biomedicines 09 01822 g004
Biomedicines 09 01822 g005 550
Figure 5. Effects of omalizumab and benralizumab on ACT score. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. * p < 0.05; **** p < 0.0001. ns: not significant.
Figure 5. Effects of omalizumab and benralizumab on ACT score. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. * p < 0.05; **** p < 0.0001. ns: not significant.
Biomedicines 09 01822 g005
Biomedicines 09 01822 g006 550
Figure 6. Effects of omalizumab and benralizumab on SNOT-22 score. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. * p < 0.05; ** p < 0.01.
Figure 6. Effects of omalizumab and benralizumab on SNOT-22 score. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. * p < 0.05; ** p < 0.01.
Biomedicines 09 01822 g006
Biomedicines 09 01822 g007 550
Figure 7. Effects of omalizumab and benralizumab on FEV1. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. * p < 0.05; ** p < 0.01. ns: not significant.
Figure 7. Effects of omalizumab and benralizumab on FEV1. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. * p < 0.05; ** p < 0.01. ns: not significant.
Biomedicines 09 01822 g007
Biomedicines 09 01822 g008 550
Figure 8. Effects of omalizumab and benralizumab on blood eosinophil counts. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. **** p < 0.0001. ns: not significant.
Figure 8. Effects of omalizumab and benralizumab on blood eosinophil counts. Comparisons were made between baseline and omalizumab, baseline and benralizumab, and omalizumab and benralizumab, respectively. **** p < 0.0001. ns: not significant.
Biomedicines 09 01822 g008
Table
Table 1. Baseline patient features.
Table 1. Baseline patient features.
CharacteristicsTotal Population (N = 20)
Female gender, N (%)13 (65)
Male gender, N (%)7 (35)
Age, mean (±SD), years52.85 ± 9.39
Asthma onset age, mean (±SD), years31.40 ± 14.34
Duration of asthma, mean (±SD), years21.85 ± 15.90
BMI, mean (±SD), % predicted23.47 ± 3.54
FEV1, mean (±SD), % predicted62.47 ± 13.84
FEV1/FVC, mean (±SD), %61.15 ± 11.65
Blood eosinophils, median value (IQR), cells/μL543.5 (360.0–1048)
Total serum IgE, median value (IQR), IU/mL274.5 (198.8–412.8)
Gastro-esophageal reflux disease, N (%)11 (55)
Chronic rhinosinusitis with nasal polyps, N (%)9 (45)
Bronchiectasis, N (%)7 (35)
Atopic dermatitis, N (%)3 (15)
Obstructive sleep apnea syndrome, N (%)2 (10)
On treatment with ICS/LABA, N (%)20 (100)
On treatment with LAMA, N (%)15 (75)
On treatment with LTRA drugs, N (%)14 (70)
Abbreviations: BMI, body mass index; FEV1, forced expiratory volume in the first second; FVC, forced vital capacity; ICS, inhaled corticosteroid; LABA, long-acting β2-adrenergic agonist; LAMA, long-acting muscarinic receptor antagonist; LTRA, leukotriene receptor antagonist; SD, standard deviation; IQR, interquartile range.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Pelaia, C.; Crimi, C.; Nolasco, S.; Carpagnano, G.E.; Brancaccio, R.; Buonamico, E.; Campisi, R.; Gagliani, C.; Patella, V.; Pelaia, G.; et al. Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy. Biomedicines 2021, 9, 1822. https://doi.org/10.3390/biomedicines9121822

AMA Style

Pelaia C, Crimi C, Nolasco S, Carpagnano GE, Brancaccio R, Buonamico E, Campisi R, Gagliani C, Patella V, Pelaia G, et al. Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy. Biomedicines. 2021; 9(12):1822. https://doi.org/10.3390/biomedicines9121822

Chicago/Turabian Style

Pelaia, Corrado, Claudia Crimi, Santi Nolasco, Giovanna Elisiana Carpagnano, Raffaele Brancaccio, Enrico Buonamico, Raffaele Campisi, Claudia Gagliani, Vincenzo Patella, Girolamo Pelaia, and et al. 2021. "Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy" Biomedicines 9, no. 12: 1822. https://doi.org/10.3390/biomedicines9121822

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop