One year of mepolizumab. Efficacy and safety in real-life in Italy
Introduction
Asthma represents one of the most common worldwide chronic diseases, affecting about 315 million of people [1]. Epidemiological studies show that the severe form of this disease occurs in about 3–10% of asthmatic patients [2]. According to ATS/ERS guidelines [3] severe asthma is characterised by poor control despite the maximal treatment, including high dose of inhaled glucocorticoids (ICS) plus a second controller (usually a long-acting β2-agonist), and/or a long-acting antimuscarinic agent, leukotriene receptor antagonist or theophylline. The definition of severe asthma also includes the need for oral corticosteroids (OCS) therapy, as a regular treatment, or taken at least twice in one year [3]. Similarly, GINA recommendations include a treatment-based severe asthma definition [4]. Moreover, regardless of the chosen severe asthma definition, a crucial role in the management of asthmatic patients, is played by the research and control of comorbidities. The most frequent comorbidities are chronic rhinosinusitis with or without nasal polyposis [5,6], gastroesophageal reflux disease [7] and bronchiectasis [8]. In addition, other conditions have been highlighted as possible comorbidities of asthma, such as obesity, sleep apnea, endocrine diseases and vocal cord disorders [9]. Some authors have also investigated the possible role of vitamin D both in childhood and in adulthood [10,11].
Despite its relatively low frequency, severe asthma has a substantial social impact, due to chronic therapy, exacerbations (commonly requiring extra visits or emergency department admissions), impairment in quality of life and OCS-related side effects [12], and is therefore responsible for a not negligible socio-economic burden. Severe asthma accounts for about 50% of the overall direct and indirect costs of the disease [13].
In the last decade, several biological treatments were introduced and investigated in the field of severe asthma, with the aim of reducing exacerbations and OCS use. A more and more detailed knowledge of asthma pathophysiology paved the way to the development of targeted molecules, in particular within the frame of Th2 inflammation, which includes interleukin (IL) 4, IL-5, IL-9, IL-13 and airway epithelial cells or innate lymphoid cells-2 [[14], [15], [16], [17]], In such case, the inflammatory background is responsive to ICS [18], which promote eosinophil apoptosis [19]. Eosinophils exert a pivotal role in bronchial inflammation and represent one of the main targets for biological drugs. Mepolizumab (MEP), a IgG1/k class humanized monoclonal antibody, blocks circulating IL-5, which is responsible for eosinophils development, maturation and survival, was marketed in the last two years [20], thus, a large experience in real-life is now available. In Italy, the regulatory Agency requires a minimum threshold of 150 eosinophils/μL before prescription and 300/μL in the previous year, in addition to the clinical criteria of severe asthma [21]. Despite the efficacy of MEP has been largely demonstrated in clinical trials only few data are available in the real-life setting [2,[22], [23], [24], [25]]. This retrospective observational study would add further data on the use of MEP in real-life.
Section snippets
Methods
We describe herein the retrospective data analysis concerning severe asthmatic patients referring to eleven severe asthma centres in Italy (Genoa, Pietra Ligure, Milan, Cuneo, Turin, Reggio Emilia, Verona, Rome, Arenzano, Brescia) and treated with MEP for at least 12 months (starting from 01st May 2017 to 31st December 2018). All centres shared a common database, which included the clinical and biological characteristics of the enrolled subjects. All patients fulfilled the criteria for severe
Results
At December 31st, 2018, 138 severe asthmatic patients (78 female; mean age 58 ± 10 years; age range 21–81), treated for at least 12 month with MEP, were included. The average onset of the disease was 34 ± 16 years (range 4–61) with a mean duration of 30 ± 21 years. Former smokers accounted for 16% of the whole sample. Mean baseline blood eosinophils level was 822 ± 491/μL at baseline, and decreased to 117 ± 96/μL after 1 year of MEP treatment (p < .0001) (Fig. 1A). Twenty seven patients (19.5%)
Discussion
Several clinical trials clearly proved the safety and efficacy of MEP. However, it is well known that real-life setting data may significantly differ from those of the clinical trials, in term of patients characteristics or follow-up and outcome modality [30]. Therefore, real-life evidence should be provided to support the results of regulatory trials, and to add new knowledge. It is noteworthy that the patients observed in real life, differ in clinical characteristics from those described in
Funding and conflict of interest
None to declare for all Authors.
Acknowledgments
CIPRO (Centro Interprofessionale Pneumologico Ricerca ed Organizzazione), Genoa.
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2021, Respiratory MedicineCitation Excerpt :Another aspect to consider is the characteristics of the populations where the efficacy of mepolizumab has been studied. Thus, the mean age varies from 51 years in the patients included in the study by Drick et al. to 59.5 years in the patients included in the Australian register; the baseline FEV1 varies from 56% in the study by Drick et al. to 76% in the study by Eger et al.; the percentage of those with atopy vary from as low as 19.5% in Bagnasco et al. to as high as 70.6% in Harvey et al., as do other characteristics that probably have a significant impact on the results [2,7,22,27]. There are some limitations to our study, which are mainly inherent to real-world studies with retrospective design.