Use of mepolizumab in adult patients with cystic fibrosis and an eosinophilic phenotype: case series

Abstract

Background: Cystic fibrosis (CF) is characterized by inflammation, progressive lung disease, and respiratory failure. Although the relationship is not well understood, patients with CF are thought to have a higher prevalence of asthma than the general population. CF Foundation (CFF) annual registry data in 2017 reported a prevalence of asthma in CF of 32%. It is difficult to differentiate asthma from CF given similarities in symptoms and reversible obstructive lung function in both diseases. However, a specific asthma phenotype (type 2 inflammatory signature), is often identified in CF patients and this would suggest potential responsiveness to biologics targeting this asthma phenotype. A type 2 inflammatory condition is defined by the presence of an interleukin (IL)-4^high, IL-5^high, IL-13^high state and is suggested by the presence of an elevated total IgE, specific IgE sensitization, or an elevated absolute eosinophil count (AEC). In this manuscript we report the effects of using mepolizumab in patients with CF and type 2 inflammation.

Results: We present three patients with CF (63, 34 and 24 year of age) and personal history of asthma, who displayed significant eosinophilic inflammation and high total serum IgE concentrations (type 2 inflammation) who were treated with mepolizumab. All three patients were colonized with multiple organisms including Pseudomonas aeruginosa and Aspergillus fumigatus and tested positive for specific IgE to multiple allergens. We examined the effect of mepolizumab on patients' lung function (FEV1), blood markers of type 2 inflammation, systemic corticosteroid use and frequency of CF exacerbations. One patient had a substantial increase in lung function after starting mepolizumab and all three patients had a substantial benefit in regards to reduced oral CCS use. While none of the patients showed significant changes in the exacerbation rates there was markedly reduced requirements for oral CCS with exacerbations. In addition, mepolizumab had a positive effect on type 2 inflammatory markers, reducing markers of allergic inflammation in all 3 patients.

Conclusions: Mepolizumab appears to have a positive effect on clinical course in patients with CF presenting with a type 2 phenotype characterized by allergic sensitization and hyper-eosinophilia.

Keywords: Allergic bronchopulmonary aspergillosis/mycosis; Asthma; Cystic fibrosis; Mepolizumab; Type 2 inflammation.

Fig. 1

Clinical course of patients receiving mepolizumab for CF with evidence of type 2 inflammation. Red and yellow arrows represent episodes of CF exacerbations associated with lung function decline, requiring intravenous or oral antibiotics, respectively. Orange triangle represents mepolizumab initiation. The yellow lines across the top of each figure represent periods of systemic corticosteroid use