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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.

SUBMITTER: Eraso IC

PROVIDER: S-EPMC7576923 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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

Eraso Isabel C IC Sangiovanni Saveria S Morales Eliana I EI Fernández-Trujillo Liliana L

Therapeutic advances in respiratory disease 20200101

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction (HR) mediated by antigens to <i>Aspergillus fumigatus</i>. 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 therap ...[more]

PMID: 33050821

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Project description:BackgroundAllergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, and their many side effects are well-documented. A group of compounds, the azoles, have activity against A fumigatus, and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been used in aerosolised form to treat invasive infection with A fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review.ObjectivesThe review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); and 2. do not have unacceptable adverse effects. If benefit was demonstrated, we planned to assess the optimal type, duration, and dose of antifungal therapy.Search methodsWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, and abstract books of conference proceedings. Date of the most recent search of the Group's Trials Register was 28 September 2021. We searched ongoing trials registries, most recently on 11 March 2022. Earlier, we also approached pharmaceutical companies regarding possible unpublished trials.Selection criteriaPublished or unpublished randomised controlled trials, in which antifungal treatments were compared to either placebo or no treatment, or where different doses of the same treatment were used in the treatment of ABPA in people with cystic fibrosis.Data collection and analysisThe searches identified six trials; none of which met the inclusion criteria for the review.Main resultsWe included no completed randomised controlled trials. There is currently one ongoing trial, which we may find eligible for a future update.Authors' conclusionsAt present, there are no randomised controlled trials that evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although one trial is currently ongoing. Trials with clear outcome measures are needed to properly evaluate the use of corticosteroids in people with ABPA and cystic fibrosis.

Project description:BackgroundCystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review.ObjectivesTo evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.Search methodsWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 09 September 2021. We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 16 August 2021.Selection criteriaRandomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.Data collection and analysisTwo review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager.Main resultsOnly one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively.Authors' conclusionsThere is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

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

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

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