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      Two years follow-up of relapsing eosinophilic pneumonia with concomitant severe asthma successfully treated with benralizumab: A case report and brief review of the literature

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      Author(s): ∗ , ,
      Publication date (Electronic):
      Journal: Respiratory Medicine Case Reports
      Publisher: Elsevier

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          Abstract

          Relapsing eosinophilic pneumonia and severe eosinophilic asthma are rare and disabling diseases, which share common inflammatory backgrounds and often require long-term systemic steroid therapy. Benralizumab is a humanized antibody targeting IL-5 receptor that reduces corticosteroid dependence and flares up in severe eosinophilic asthma on long term. In this case report, successful treatment of eosinophilic pneumonia and severe eosinophilic asthma with benralizumab is described after a 2-year follow up, showing the promising results of this therapy for eosinophilic pneumonia management.

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          Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma.

          Parameswaran Nair, Sally Wenzel, Klaus F Rabe … (2017)
          Background Many patients with severe asthma rely on oral glucocorticoids to manage their disease. We investigated whether benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor that significantly reduces the incidence of asthma exacerbations, was also effective as an oral glucocorticoid-sparing therapy in patients relying on oral glucocorticoids to manage severe asthma associated with eosinophilia. Methods In a 28-week randomized, controlled trial, we assessed the effects of benralizumab (at a dose of 30 mg administered subcutaneously either every 4 weeks or every 8 weeks [with the first three doses administered every 4 weeks]) versus placebo on the reduction in the oral glucocorticoid dose while asthma control was maintained in adult patients with severe asthma. The primary end point was the percentage change in the oral glucocorticoid dose from baseline to week 28. Annual asthma exacerbation rates, lung function, symptoms, and safety were assessed. Results Of 369 patients enrolled, 220 underwent randomization and started receiving benralizumab or placebo. The two benralizumab dosing regimens significantly reduced the median final oral glucocorticoid doses from baseline by 75%, as compared with a reduction of 25% in the oral glucocorticoid doses in the placebo group (P<0.001 for both comparisons). The odds of a reduction in the oral glucocorticoid dose were more than 4 times as high with benralizumab as with placebo. Among the secondary outcomes, benralizumab administered every 4 weeks resulted in an annual exacerbation rate that was 55% lower than the rate with placebo (marginal rate, 0.83 vs. 1.83, P=0.003), and benralizumab administered every 8 weeks resulted in an annual exacerbation rate that was 70% lower than the rate with placebo (marginal rate, 0.54 vs. 1.83, P<0.001). At 28 weeks, there was no significant effect of either benralizumab regimen on the forced expiratory volume in 1 second (FEV1), as compared with placebo. The effects on various measures of asthma symptoms were mixed, with some showing significant changes in favor of benralizumab and others not showing significant changes. Frequencies of adverse events were similar between each benralizumab group and the placebo group. Conclusions Benralizumab showed significant, clinically relevant benefits, as compared with placebo, on oral glucocorticoid use and exacerbation rates. These effects occurred without a sustained effect on the FEV1. (Funded by AstraZeneca; ZONDA ClinicalTrials.gov number, NCT02075255 .).
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            Population-based assessment of adverse events associated with long-term glucocorticoid use.

            Jeffrey Curtis, Andrew Westfall, Jeroan Allison … (2006)
            The frequency of many adverse events (AEs) associated with low-dose glucocorticoid use is unclear. We sought to determine the prevalence of glucocorticoid-associated AEs in a large US managed care population. Using linked administrative and pharmacy claims, adults receiving >or=60 days of glucocorticoids were identified. These individuals were surveyed about glucocorticoid use and symptoms of 8 AEs commonly attributed to glucocorticoid use. Of the 6,517 eligible glucocorticoid users identified, 2,446 (38%) returned the mailed survey. Respondents were 29% men with a mean +/- SD age of 53 +/- 14 years; 79% were white and 13% were African American. Respondents had a mean +/- SD of 7 +/- 3 comorbid conditions and were prescribed a mean +/- SD prednisone-equivalent dosage of 16 +/- 14 mg/day. More than 90% of individuals reported at least 1 AE associated with glucocorticoid use; 55% reported that at least 1 AE was very bothersome. Weight gain was the most common self-reported AE (70% of the individuals), cataracts (15%) and fractures (12%) were among the most serious. After multivariable adjustment, all AEs demonstrated a strong dose-dependent association with cumulative glucocorticoid use. Among users of low-dose therapy (
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              Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines ‐ recommendations on the use of biologicals in severe asthma

              Ioana Agache, Jessica Beltran, Cezmi Akdis … (2020)
              Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV1 , without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV1 . More data on long-term safety are needed together with more efficacy data in the paediatric population.
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                Author and article information

                Contributors
                G. Angeletti
                Journal
                Journal ID (nlm-ta): Respir Med Case Rep
                Journal ID (iso-abbrev): Respir Med Case Rep
                Title: Respiratory Medicine Case Reports
                Publisher: Elsevier
                ISSN (Electronic): 2213-0071
                Publication date PMC-release: 13 December 2022
                Publication date Collection: 2023
                Publication date (Electronic): 13 December 2022
                Volume: 41
                Electronic Location Identifier: 101795
                Affiliations
                [1]Department of Respiratory Medicine, Bellaria Hospital, Bologna, Italy
                Author notes
                [∗ ]Corresponding author. giulia.angeletti@ 123456ausl.bologna.it
                Article
                Publisher Item ID: S2213-0071(22)00217-9 Publisher ID: 101795
                DOI: 10.1016/j.rmcr.2022.101795
                PMC ID: 9791164
                PubMed ID: 36579077
                SO-VID: d747ec47-2860-40a4-a8fa-91e9f3d24b10
                Copyright © © 2022 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 8 August 2022
                Date accepted : 12 December 2022
                Categories
                Subject: Case Report

                Data availability:

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