Eosinophilic granulomatosis with polyangiitis remission achieved with benralizumab
Key takeaways:
- Patients began with mepolizumab or benralizumab before switching to continuing with benralizumab at week 52.
- About 44% of patients stopped using oral glucocorticoids.
- Blood eosinophil counts fell as well.
SAN DIEGO — Remission persisted through 104 weeks for most patients with eosinophilic granulomatosis with polyangiitis who used benralizumab, according to a poster presented here.
Lower blood eosinophil counts also persisted through this timeframe, David J. Jackson, PhD, MSc, consultant, Guy’s Severe Asthma Centre, Guy’s and St. Thomas’ NHS Trust, told Healio at the 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress.
“MANDARA was the first ever head-to-head of type 2 biologics in any disease,” Jackson said.
The study compared the use of mepolizumab (Nucala, GSK), an anti-IL-5 biologic, with benralizumab (Fasenra, AstraZeneca), which targets IL-5 receptors, in treating eosinophilic granulomatosis with polyangiitis (EPGA).
“They’re similar drugs but distinct in the sense that IL-5 mepolizumab is a serum-neutralizing antibody, so it doesn’t completely deplete eosinophils,” Jackson said.
But benralizumab opposes any cell that expresses the IL-5 receptor, so it achieves a more rapid and complete depletion of eosinophils, he continued.
“So mechanistically, the question has always been, does that additional eosinophil suppression matter clinically or not?” Jackson said. “Is it advantageous, or is this eosinophil suppression with mepolizumab sufficient?”
The 52-week, double-blind MANDARA study randomly assigned 140 adults with EPGA 1:1 to subcutaneous doses of benralizumab (30 mg) or mepolizumab (300 mg) every 4 weeks. These patients also required 7.5 mg or more of stable oral glucocorticosteroids each day and/or stable immunosuppressive therapy before beginning the study.
At week 52, 25.8% of the mepolizumab group and 40.9% of the benralizumab group achieved complete withdrawal of oral glucocorticosteroids.
“In the original phase 3 of the MANDARA study, it just simply showed noninferiority [benralizumab] vs. [mepolizumab],” Jackson said. “The only thing that came out of interest was the fact that on benralizumab, more patients had completely come off of prednisolone. But otherwise, it was noninferior.”
In the MANDARA open-label extension, 66 patients (mean age, 52.5 years; 63.6% female) continued to receive benralizumab and 62 (mean age, 53 years; 56.5% female) switched from mepolizumab to benralizumab, both for 52 weeks.
At the end of the open-label extension, 43.9% of those who were on benralizumab for the full study and 43.5% of those who switched from mepolizumab to benralizumab achieved complete withdrawal of oral glucocorticoids.
“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 said.
Defined as a Birmingham Vasculitis Activity Score of 0 and an oral glucocorticosteroid dose of 4 mg a day or less, 71% of the mepolizumab group and 68.2% of the benralizumab group achieved remission at 52 weeks. Rates fell to 67.7% for the group that switched from mepolizumab to benralizumab and to 62.1% for the group that remained on benralizumab at 104 weeks.
Median absolute blood eosinophil counts fell from almost 250 cells/µL for the benralizumab group and approximately 200 cells/µL for the mepolizumab group at baseline to approximately 25 cells/µL for both groups at the end of the study as well.
“Mechanistically, it basically just highlights the central role of the eosinophil in this disease,” Jackson said.
Also, 77.3% of the patients who stayed on benralizumab through the open-label extension and 67.7% of those who switched from mepolizumab to benralizumab did not experience any relapses.
While 97% of the patients who stayed on benralizumab and 100% of the patients who switched from mepolizumab to benralizumab experienced adverse events, only 22.7% of the benralizumab group and 35.5% of the mepolizumab group experienced serious adverse events.
“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,” Jackson said.
Jackson also noted that mepolizumab requires three monthly injections and benralizumab only requires one, which could be an advantage for patients who are not comfortable with needles.
“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,” he said.
Jackson also is optimistic about benralizumab’s future role in therapy.
“It should be first-line therapy. It will emerge in all the guidelines as really the first-line therapy now,” he said. “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.”
In the meanwhile, he added, research will continue.
“Next, we need to understand what the differences are between the two-thirds of patients that do have remission and the one-third that doesn’t,” he said. “And for the one-third that doesn’t achieve remission, what is the potentially better treatment?”