Use of monoclonal antibodies for allergic bronchopulmonary aspergillosis in patients with asthma and cystic fibrosis: literature review

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction (HR) mediated by antigens to Aspergillus fumigatus. It is estimated that 2–15% of patients with cystic fibrosis (CF) and between 1% and 5% of asthmatics develop ABPA, affecting approximately 4.8 million people worldwide. The goals of treatment are controlling inflammation, reducing the number of exacerbations and limiting the progression of lung damage. Systemic steroids are therefore used as the mainstay therapy, along with antifungal medications. However, many patients do not respond or develop side effects to treatment. In this scenario, biological drugs such as Omalizumab, Mepolizumab, Benralizumab and Dupilumab have been implemented in clinical practice, even though there is a lack of scientific evidence to support their use. We performed a literature review of the studies carried out which analyzed biologics for the management of ABPA in adult populations with asthma and CF. To our knowledge this is the first literature review that included all biologics. We included a total of 32 studies, all but one were descriptive studies, and the vast majority evaluated the use of Omalizumab. Biologics appeared to have more benefit for patients with ABPA and asthma than CF, specifically at decreasing the frequency of acute exacerbations and by having a steroid-sparing effect. Although a decrease in serum IgE level is considered a measure of therapy success, values may not decline as expected in the context of a significant clinical improvement, highlighting the importance of measuring patient-oriented outcomes. As evidence comes mainly from case series and case reports, randomized controlled trials are needed to evaluate further the safety and efficacy of biologics in ABPA. The reviews of this paper are available via the supplemental material section.

Mepolizumab and dupilumab as a replacement to systemic glucocorticoids for the treatment of Chronic Eosinophilic Pneumonia and Allergic Bronchopulmonary Aspergillosis - Case series, Almoosa specialist hospital

“…In recent years, several studies and case reports have demonstrated the efficacy of anti-IgE antibodies and interleukin-5/interleukin-5 receptor-alpha (IL5/IL5-Rα) antibodies in the treatment of ABPA but was more beneficial for patients with asthma than for patients with CF [ [29] , [30] , [31] , [32] ]. Mepolizumab has been successfully used to treat patients with ABPA, showing improvement in FEV1, radiographic findings, decrease in total IgE levels, and quality of life without side effects and is considered a glucocorticoid-sparing agent [ [29] , [33] , [34] , [35] , [36] , [37] , [38] , [39] ]. Altman et al reported that combination therapy with both omalizumab and mepolizumab improved ABPA, and together they may have a potential synergistic effect [ 31 ].…”

“…ALI et al [ 41 ] and Mikura et al [ 42 ] reported a case of ABPA treated successfully with dupilumab. Two studies also evaluated dupilumab in 21 asthma patients treated for ABPA - IgE levels decreased by 35% from baseline and annual exacerbation rates decreased in 95% of patients [ 29 ]. Our patients with ABPA were treated with mepolizumab and dupilumab instead of omalizumab because of the high IgE levels they had.…”

Factors Contributing to Sex Differences in Mice Inhaling Aspergillus fumigatus

“…The IgE effector functions are activated by its binding to Fc receptors FcɛRI and FcɛRII/CD23 [54]. Previous studies have shown that IgE antibodies triggered against A. fumigatus antigens can degranulate mast cells [55], and the biologics (Omalizumab) targeting IgE show variable effects in the clinic [56]. We observed serum IgE antibody titers to be elevated in female mice (p = 0.067) challenged with A. fumigatus, relative to naïve and male mice, at day 28 post-challenge.…”

Future Directions for Clinical Respiratory Fungal Research

“…The identification of specific clinically relevant disease endotypes has been greatly accelerated in respiratory medicine through the advent of systematic immunophenotyping studies [95, [139][140][141][142]. Given the current revolution in monoclonal antibody therapies in clinical medicine, with many agents now licensed for therapy of asthma and allergic rhinitis, repurposing of these monoclonals for allergic fungal airway diseases in particular, and better understanding of which may be more efficacious in this setting, is a current high priority [143,144]. We are already using omalizumab routinely for IgE depletion in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization, with accumulating but mainly case series-based clinical data to support this approach [145][146][147].…”