The first head-to-head comparison of type 2 biologics in any disease has revealed promising long-term outcomes for patients with eosinophilic granulomatosis with polyangiitis (EGPA) treated with benralizumab, according to new data from the MANDARA study extension presented at the 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress.
Extended Remission Rates Maintained
In the open-label extension phase, 62.1% of patients who remained on benralizumab achieved remission at 104 weeks, defined as a Birmingham Vasculitis Activity Score of 0 and an oral glucocorticosteroid dose of 4 mg per day or less. Among patients who switched from mepolizumab to benralizumab, 67.7% achieved remission by the study's end.
"The majority of patients had a very good response, were able to come off prednisolone, remained relapse free, in disease remission, with no significant side effects," said David J. Jackson, PhD, MSc, consultant at Guy's Severe Asthma Centre, Guy's and St. Thomas' NHS Trust.
The extension study included 66 patients who continued benralizumab treatment and 62 patients who switched from mepolizumab to benralizumab, both groups receiving treatment for an additional 52 weeks beyond the initial study period.
Steroid-Sparing Effects Persist
Complete withdrawal from oral glucocorticosteroids was achieved by 43.9% of patients who remained on benralizumab throughout the full study period and 43.5% of those who switched from mepolizumab to benralizumab. This represents a notable improvement from the initial 52-week results, where 40.9% of benralizumab patients and 25.8% of mepolizumab patients achieved complete steroid withdrawal.
"By the end of the year, the second year now, there's an equivalent number of patients who have been able to completely come off prednisolone," Jackson noted, highlighting the convergence of outcomes between treatment groups over time.
Mechanistic Advantages of IL-5 Receptor Targeting
The study underscores the clinical significance of benralizumab's distinct mechanism of action compared to mepolizumab. While mepolizumab functions as a serum-neutralizing antibody against IL-5 and doesn't completely deplete eosinophils, benralizumab targets any cell expressing the IL-5 receptor, achieving more rapid and complete eosinophil depletion.
Median absolute blood eosinophil counts fell from approximately 250 cells/μL for the benralizumab group and 200 cells/μL for the mepolizumab group at baseline to approximately 25 cells/μL for both groups at study completion.
"Mechanistically, it basically just highlights the central role of the eosinophil in this disease," Jackson explained, emphasizing how the sustained eosinophil suppression correlates with clinical benefits.
Safety Profile and Relapse Prevention
The safety profile remained favorable throughout the extended treatment period. While 97% of patients continuing benralizumab and 100% of those switching from mepolizumab experienced adverse events, only 22.7% of the benralizumab group experienced serious adverse events compared to 35.5% in the original mepolizumab group.
Relapse prevention was robust, with 77.3% of patients who remained on benralizumab and 67.7% of those who switched from mepolizumab experiencing no relapses during the extension period.
Real-World Evidence Supports Clinical Benefits
Complementary real-world data from a separate retrospective cohort study of 114 EGPA patients treated with mepolizumab provides additional context for IL-5 pathway inhibition benefits. The study, published in Annals of Allergy, Asthma & Immunology, demonstrated significant improvements across multiple disease burden measures.
Mean daily oral corticosteroid doses decreased by 18%, from 7.8 mg to 6.4 mg, while the number of oral corticosteroid dispensations fell by 18% and corticosteroid bursts decreased by 50%. EGPA-related hospitalizations dropped by 49%, from 1.55 to 0.86 per person-year, and asthma exacerbation rates fell by 42%.
Clinical Implications and Future Positioning
Jackson expressed optimism about benralizumab's emerging role in EGPA treatment, stating, "It should be first-line therapy. It will emerge in all the guidelines as really the first-line therapy now. By far, you've got the best evidence base compared with any of the other therapies we use in this disease, and fortunately, it's very safe."
The practical advantage of benralizumab's monthly dosing schedule versus mepolizumab's requirement for three monthly injections may also influence treatment decisions. "If you have the option of sticking 12 needles in your leg over a year or 36, you'll take 12, all other things being equal," Jackson noted.
Addressing Unmet Medical Needs
EGPA, formerly known as Churg-Strauss syndrome, is characterized by inflammation of small and medium-sized blood vessels and eosinophil overproduction, leading to widespread inflammation and organ damage, particularly affecting the lungs, nerves, skin, and gastrointestinal tract.
The disease presents significant challenges for patients, often beginning with severe, worsening asthma and persistent sinus issues before progressing to seemingly unrelated problems such as nerve pain, skin rashes, and extreme fatigue.
Future research priorities include understanding the differences between the two-thirds of patients who achieve remission and the one-third who don't, as well as identifying potentially better treatments for non-responders. The research community continues to investigate longer follow-up periods, larger cohorts, and comparative effectiveness studies to further optimize EGPA management strategies.
