Clinical Pearls & Morning Reports

Posted by Carla Rothaus, MD

Published March 6, 2024


How did benralizumab compare with mepolizumab regarding disease remission in the trial by Wechsler et al.?

Wechsler et al. conducted a phase 3 trial that evaluated the efficacy and safety of 52 weeks of benralizumab as compared with mepolizumab in patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA) who were also receiving standard therapy. Read the NEJM Original Article here.

Clinical Pearls

Q: Describe some of the features of EGPA.

A: EGPA is a rare inflammatory disorder characterized by asthma, necrotizing vasculitis, extravascular granulomas, and blood and tissue eosinophilia. Oral glucocorticoids and immunosuppressive drugs have long been the cornerstone of treatment for EGPA, despite burdensome side effects. However, although prolonged treatment with oral glucocorticoids reduces the risk of relapse, it is associated with progressive toxic effects. Relapse is also common during oral glucocorticoid tapering, and patients are often unable to fully discontinue treatment.

Q: Do benralizumab and mepolizumab have the same mechanism of action?

A: The targeting of eosinophilic inflammation is a well-recognized strategy for the treatment of EGPA. A previous clinical trial showed that treatment of EGPA with mepolizumab, a monoclonal antibody that inhibits eosinophil activation and differentiation by binding interleukin-5, resulted in a longer duration of remission, a higher percentage of patients entering remission, a lower percentage of patients having relapse, and less use of oral glucocorticoids than placebo. On the basis of these findings, mepolizumab was the first targeted therapy approved for EGPA. Benralizumab is a humanized, afucosylated monoclonal antibody with high affinity and specificity for the human interleukin-5 receptor α subunit (interleukin-5Rα) expressed on eosinophils and is approved for the treatment of severe eosinophilic asthma.

Morning Report Questions

Q: How did benralizumab compare with mepolizumab regarding disease remission in the trial by Wechsler et al.?

A: The adjusted percentage of patients with remission at weeks 36 and 48 (the primary outcome) was 59% in the benralizumab group and 56% in the mepolizumab group (difference, 3 percentage points; 95% confidence interval [CI], –13 to 18; P = 0.73 for superiority), showing noninferiority but not superiority of benralizumab to mepolizumab, since the lower bound of 95% confidence interval exceeded −25 percentage points and the P value for superiority was greater than 0.05. In both groups, 30% of patients had a relapse, and the time to first relapse was similar in the two groups (hazard ratio, 0.98; 95% CI, 0.53 to 1.82).

Q: What were some of the safety outcomes of the trial?

A: The safety profile of benralizumab did not show any meaningful difference from that of mepolizumab and was similar to the safety profile that had previously been observed in trials involving patients with severe eosinophilic asthma. Adverse events were reported in 90% of the patients who received benralizumab and 96% of those who received mepolizumab. The most often reported adverse events were coronavirus disease 2019 (in 21% of the patients in the benralizumab group and 27% of those in the mepolizumab group), headache (17% and 16%), and arthralgia (17% and 11%). No patients in the benralizumab group had adverse events leading to treatment discontinuation. Serious adverse events were reported in 6% of the patients in the benralizumab group and 13% of those in the mepolizumab group.

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