Use of Biologic Drugs for Treatment of Allergic Bronchopulmonary Aspergillosis

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic fungal infection that induces immunoglobulin E (IgE) production and eosinophils proliferation and affect mostly asthmatic and cystic fibrosis patients. The mainstay treatment for ABPA is systemic steroid and antifungal treatment which have increasing rates of treatment failure and side effects. Because of their mechanism of action in suppressing IgE or eosinophils, biologic drugs were expected to play an important role in the treatment of ABPA, however, their use in this issue was off label and lack the evidence. In this comprehensive and comparative review, 59 full text articles (228 patients) were selected. The outcomes were analyzed and the percentages of posttreatment change for each variable in each study were collected then the overall median percentages were calculated for each variable for each biologic drug. Comparative discussion of these outcomes was done in terms of clinical and functional response, reduction of exacerbation events, reduction of IgE level and eosinophils count, prevention of complications and patient's ability to reduce steroid dose or discontinue it.The review shows that the use of biologic drugs for treatment of ABPA is associated with a significant clinical and functional improvement and reduction of exacerbation rates up to 90%. There is more reduction in post-treatment IgE level with mepolizumab and marked reduction in posttreatment eosinophils count with benralizumab. Mepolizumab has the better steroid-sparing effect. Changing from one biologic drug to another with different target in case of treatment failure is advisable. More stronger studies and randomized control trials are needed to figure out the use of biologic drugs for ABPA treatment.

Severe Fungal Asthma: A Role for Biologics and Inhaled Antifungals

“…In a comprehensive review encompassing qualitative analysis of 49 studies ( n = 267) and quantitative meta-analysis of 14 case series ( n = 167), omalizumab for ABPA significantly (a) reduced annualized exacerbation rate versus pre-treatment, (b) reduced oral steroid use and dose, (c) increased wean off steroids, (d) improved lung function and (e) improved asthma control [ 64 ]. In the aggregate, most patients receiving a T2-targeting Mab for ABPA showed reduction in exacerbation rate and a steroid-sparing effect along with reduction in total IgE and eosinophila, with less consistent effects on lung function and patient-reported outcome instruments [ 64 , 65 , 66 , 67 ]. In several cases that were reported with serial chest computed tomographic imaging, pulmonary infiltrates—presumed eosinophilic mucoid impaction and mucus plugs associated with Aspergillus sensitization and more severe asthma phenotype [ 29 ]—cleared soon after initiation of Mab treatment [ 68 , 69 , 70 , 71 , 72 , 73 ].…”

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses

“…In the last two decades, several trials of monoclonal antibodies against IgE, interleukin (IL)-5, IL-5 receptor (IL-5R), IL-4 receptor α (IL-4Rα) and thymic stromal lymphopoietin (TSLP) have demonstrated clinical benefit in severe eosinophilic asthma [ 158 – 161 ]. Biological agents are likely helpful in stable treatment-dependent ABPA based on case reports and small case series [ 41 , 134 , 162 ]. Omalizumab is a potential therapeutic approach since ABPA is associated with elevated IgE levels.…”

“…Omalizumab is a potential therapeutic approach since ABPA is associated with elevated IgE levels. Mepolizumab (anti-IL-5), benralizumab (anti-IL-5R), dupilumab (anti-IL-4Rα) and tezepelumab (anti-TSLP) have also been used in ABPA patients [ 135 , 142 , 162 – 165 ]. Most experience of biological agents in ABPA is with omalizumab.…”

A Case of Allergic Bronchopulmonary Aspergillosis With Failure of Benralizumab and Response to Dupilumab

“…In particular, the side effects of long-term steroid use are often a clinical problem. In this context, it is noteworthy that the use of biological agents not only provides clinical and functional improvement but also offers a high potential for reducing or discontinuing systemic steroids [ 6 ]. Each of these biological agents targets the specific molecules associated with asthma exacerbations: e.g., benralizumab is an anti-IL-5 receptor alpha (IL-5Rα) monoclonal antibody, and dupilumab targets IL-4Rα, a common subunit of receptors for IL-4 and IL-13, which inhibits the signaling of both cytokines.…”