January 2025

This brief review aims to provide an overview of the evidence from the recently published meta-analysis by Spataro et al., which evaluated benralizumab—a biologic targeting the IL-5 receptor α—as a potential therapeutic option for EGPA, reporting encouraging outcomes. This monoclonal antibody was approved by the FDA for adults with EGPA in September 2024. The meta-analysis synthesized data from eight studies involving 396 patients, incorporating one randomized controlled trial and seven observational research. Benralizumab demonstrated substantial clinical benefits, notably reducing oral corticosteroid use by an average of 8 mg/day and achieving remission in 57% of patients. Additionally, 28% of participants were able to discontinue immunosuppressants, while adverse events occurred in 22% of cases, with only one patient discontinuing due to side effects. Younger patients showed a more pronounced reduction in corticosteroid use compared to older individuals, possibly due to a stronger immune response or shorter disease duration, highlighting the potential advantages of early treatment.

A key strength of the analysis lies in its inclusion of diverse data sources, which enhances the generalizability of findings. By examining outcomes such as steroid-sparing effects, remission rates, and safety profiles, the study underscores the multifaceted benefits of benralizumab. However, limitations include the reliance on a single randomized controlled trial and different definitions of remission, which may affect the interpretation of results.

Despite these limitations, the findings strongly support benralizumab as a promising therapy for EGPA, particularly for younger patients. Larger, multicenter trials are needed to confirm its long-term efficacy and safety. Future research should also prioritize the identification of biomarkers to predict treatment response and further investigate age-related differences in efficacy.

Overall, this meta-analysis highlights the pivotal role of eosinophils in EGPA pathogenesis and the therapeutic potential of targeting the IL-5 pathway. Benralizumab not only improves clinical outcomes but also reduces reliance on corticosteroids and immunosuppressants, minimizing treatment-related risks and offering a significant advancement in EGPA management.

In the reviewed study, the authors explored whether benralizumab, an interleukin-5 receptor-α monoclonal antibody, could outperform OCS for treating eosinophilic exacerbations of asthma and COPD.

ABRA (Acute exacerbations treated with BenRAlizumab) was a multicenter, double-blind, double-dummy, placebo-controlled trial involving 158 patients experiencing eosinophilic (blood eosinophils ≥300 cells/µL) asthma or COPD exacerbations. Participants received either benralizumab (100 mg subcutaneously×1), prednisone (30 mg once daily for 5 days), or a combination. The co-primary outcomes were treatment failure at 90 days and symptom improvement measured by a visual analogue scale (VAS) at day 28.

The study included 88 (56%) patients with asthma and 51 (32%) with COPD exacerbations. Treatment failure occurred in 74% in the prednisone group and 45% when both benralizumab groups were pooled (OR 0.26 [95% CI 0.13-0.56]; p=0.0005). The total VAS symptoms score was significantly better in the pooled-benralizumab group compared with the prednisone group (mean difference, 49 mm [95% CI 14–84]; p=0.0065).

At day 28, time to first treatment failure event was significantly longer in the pooled-benralizumab group than in the prednisone group (p=0.0003), without differences between benralizumab and benralizumab+prednisone groups (p=0.68). ACQ-7 and AQLQ scores were significantly better in the pooled-benralizumab group. Lung function improved across all treatment groups. In post-hoc subgroup analysis, time to treatment failure favored pooled-benralizumab irrespective of age, sex, disease, baseline FEV₁, or biomarkers at exacerbation. Adverse events occurred in 91% of patients in the prednisone group and 76% in the pooled-benralizumab group, with hyperglycemia and sinusitis only occurring with prednisone.

Strengths of this study include its endotype-driven approach (e.g., selecting patients based on high blood eosinophil levels at the time of the exacerbations). While the study is interesting, there are several limitations, including the phase 2 design with a relatively small size of the cohorts and inclusion of only two enrollment centers. The study pooled the benralizumab cohorts and provided no information about the effect of benralizumab with or without concurrent prednisone treatment. Additionally, the study did not differentiate outcomes between asthma and COPD attacks. These preliminary findings prompt further investigation, such as a detailed phase 3 trial.