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

Abstract

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.

Considerations on biologicals for patients with allergic disease in times of the COVID‐19 pandemic: An EAACI statement

“…Recent systematic reviews on approved biologicals in severe asthma showed that biologicals targeting IL‐5‐signaling pathway (mepolizumab, reslizumab, and benralizumab) slightly increase drug‐related adverse events (AE) in severe eosinophilic asthma 36 . For anti‐IgE (omalizumab) and anti‐IL‐4Rα (dupilumab) treatments, rate ratios were rather small 36 . Benralizumab and omalizumab showed an increase in AEs with low‐to‐moderate certainty in severe allergic asthma 37 .…”

Onion Bulb Extract Downregulates EGFR/ERK1/2/AKT Signaling Pathway and Synergizes With Steroids to Inhibit Allergic Inflammation

“…The recent introduction of monoclonal antibodies targeting the eosinophil chemoattractant underscores the importance of eosinophils in asthma ( Agache et al, 2020 ). Our data show that treatment with OBE significantly reduced eosinophil numbers not only in the tissue but also their ex vivo chemotaxis towards BAL fluid from HDM challenged mice.…”

“…Similarly, the use of the newly introduced anti-IL5 antibodies such as mepolizumab and benralizumab is limited to severe asthmatics with a high eosinophilic component. However concerns have been raised regarding their cost-effectiveness ( Agache et al, 2020 ). Despite the recent market increase in therapeutic agents that selectively target specific molecules, it is unlikely that the blockade of individual mediator signaling pathways would result in optimal therapeutic outcomes in asthma, and monoclonal based therapy would certainly be beyond the financial reach of most asthma patients in the developing world due to their high cost.…”

The Role of Cannabinoids in Allergic Diseases: Collegium Internationale Allergologicum (CIA) Update 2020

“…However, in patients with severe asthma, the treatment of the disease is still challenging [106,107]. Over the last years, biologicals have significantly improved the asthma control and quality of life of many severe asthma patients, but novel safe and cost-effectiveness treatments are still demanded [109][110][111].…”