Mepolizumab as Possible Treatment for Allergic Bronchopulmonary Aspergillosis: A Review of Eight Cases

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is an eosinophilic pulmonary disorder caused by a hypersensitivity reaction to Aspergillus fumigatus that manifests with uncontrolled asthma, peripheral blood eosinophilia, and radiological findings, such as mucus plugging. Early diagnosis and proper treatment of ABPA are essential to prevent irreversible lung damage such as pulmonary fibrosis and bronchiectasis and improve the quality of life of patients. Beside inhaled medication for asthma, anti-inflammatory agents (i.e., systemic glucocorticoids) and antifungal agents are the mainstay treatment of ABPA. The goal of therapy using glucocorticoids and antifungal agents is to suppress the immune hyperreactivity to A. fumigatus and attenuate the fungal burden. Since the systemic glucocorticoid therapy may lead to serious adverse effects including osteoporosis, avascular necrosis, myopathy, cushingoid appearance, hypertension, insomnia, and increased risk of infection, a glucocorticoid-sparing agent could be considered. Mepolizumab is a humanized monoclonal antibody that binds to interleukin-5, which is the key mediator for eosinophil differentiation, activation, migration, and survival. We review eight cases of ABPA treated successfully with mepolizumab. Treatment with mepolizumab was not restricted to the total immunoglobulin E level, the limiting factor for omalizumab in ABPA. In addition, mepolizumab therapy improved forced expiratory volume in one second, radiological findings, and patient quality of life.

Use of Biologic Drugs for Treatment of Allergic Bronchopulmonary Aspergillosis

“…In addition, omalizumab leads to reduction in high-affinity IgE receptor expression on mast cells, basophils, and dendritic cells [86][87][88]. The median reduction rates in IgE level after treatment were 67% and 65% for mepolizumab and dupilumab respectively, which are surprisingly higher than that in omalizumab although both mepolizumab and dupilumab are not working on IgE like omalizumab and the baseline IgE level is not required to initiate them [57][58][59][60][61][62][63][64][65][66][67][68][69][76][77][78][79][80][81]. The median reduction rate in eosinophiles count was higher with bernalizumab (99%) compared to other biologic drugs [70][71][72][73][74][75].…”

“…There was a functional improvement in FEV-1 value after treatment seen with all biologic treatments but was not as significant as expected when correlated to the clinical improvement, and this might be attributed to other confounding factors such as timing of procedure, disease severity and patients' factors. However, mepolizumab showed the higher rate of functional improvement from the baseline compared to other biologic drugs [57][58][59][60][61][62][63][64][65][66][67][68][69]. Majority of patient were able to reduce the maintenance steroid dose or discontinue it, with the higher rate was reported with mepolizumab (98% of patients), to be the most effective steroid sparing agent among other biologic drugs.…”

“…Majority of patient were able to reduce the maintenance steroid dose or discontinue it, with the higher rate was reported with mepolizumab (98% of patients), to be the most effective steroid sparing agent among other biologic drugs. [57][58][59][60][61][62][63][64][65][66][67][68][69]. The use of combination of two or more biologic drugs or shifting from one to another was described in the literature [65,72,74,78,79].…”

“…Mepolizumab is a humanized recombinant IgG1 monoclonal antibody that blocks interleukin-5 (IL-5). In ABPA treatment, Mepolizumab led to reduction in the total IgE level by a median of 67% and reduction in eosinophiles count by a median of 95% from baseline after a treatment period ranging from 6 to 24 months [57][58][59][60][61][62][63][64][65][66][67][68][69]. There was an improvement in lung function and FEV-1 noticed in most studies and there was also a reduction in annual exacerbation rate in 85% of patients and 98% of patients were able either to reduce the dose of systemic steroid or stop it [57][58][59][60][61][62][63][64][65][66][67][68][69].…”

A case of allergic bronchopulmonary aspergillosis with marked peripheral blood eosinophilia successfully treated with benralizumab

“…Another review presented eight ABPA cases, treated successfully with mepolizumab. Mepolizumab improved pulmonary function, radiological findings, and quality of life [ 4 ]. Excluding our patient, only four cases have been described for the use of benralizumab [ [5] , [6] , [7] ].…”