One year of mepolizumab. Efficacy and safety in real-life in Italy

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Abstract

Background

Severe asthma is a disease with a heavy socio-economic burden and a relevant impact on the life of patients. Mepolizumab (MEP) was recently introduced in practice. The previous data were favourable as efficacy and safety are concerned. Nowadays, we can report the clinical data after more than one year of use of MEP in the real-life setting.

Objective

To evaluate the efficacy and safety of MEP in a real life framework, mainly concerning asthma exacerbations, steroid dependence, effects on respiratory function and adverse events.

Methods

This retrospective analysis was performed on 138 patients, treated with MEP for at least 12 months, and referred to eleven severe asthma clinics in Italy. All patients met the criteria for severe uncontrolled asthma according to ATS/ERS guidelines and prescribing MEP conditions according to the Italian Drug Agency (AIFA).

Results

We could observe 138 patients (78 female, age 58 ± 10 years). The average age of onset of asthma was 34 ± 16 years. The blood eosinophil count decreased from 822 ± 491/μL at baseline to 117 ± 96/μL (p < .0001) after 12 months of therapy. Exacerbations decreased from 3.8/year to 0.7/year (−81%; p < .0001). Steroid-dependent patients before MEP (80%) with a daily dose of 10.1 ± 9.4 mg prednisone decrease at 28% after 12 months with a mean of 2.0 ± 4.2 mg/day (p < .0001). The occurrence of adverse events was overall low.

Conclusions & clinical relevance

In this real-life setting, MEP confirmed its efficacy and safety profile, already shown in clinical trials. This was apparent concerning exacerbation rate, systemic steroids intake and safety.

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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