Anti-IL-5 Therapy Holds Remission in EGPA Through Week 104
Two years of anti-interleukin-5/receptor therapy kept a substantial share of patients with eosinophilic granulomatosis with polyangiitis in remission while pushing oral glucocorticoid exposure lower over time. The MANDARA extension followed patients beyond the 52-week double-blind period and tracked the elements that matter most in this disease: vasculitis activity, steroid dependence, eosinophil depletion, relapse, and safety. In a disorder where asthma, sinus disease, neuropathy, and systemic vasculitis can flare in overlapping waves, a durable biologic effect has direct bedside value.
The open-label extension enrolled 128 patients, including 66 who continued benralizumab and 62 who switched from mepolizumab to benralizumab. At week 104, remission rates remained high in both groups: 41 patients, or 62.1%, in the benralizumab/benralizumab arm and 42 patients, or 67.7%, in the mepolizumab/benralizumab arm. The remission definition was strict, combining a Birmingham Vasculitis Activity Score of 0 with an oral glucocorticoid dose of 4 mg/day or less. In practical terms, this is not a soft symptom endpoint; it reflects full suppression of measurable vasculitis activity with near-minimal steroid exposure.
The trajectory of relapse also stayed favorable. During the first year of the extension, 51 patients in the benralizumab/benralizumab group and 42 in the mepolizumab/benralizumab group had no relapses, corresponding to 77.3% and 67.7%, respectively. For a disease that can reassert itself quickly when eosinophilic inflammation rebounds, maintaining this level of control over many months suggests sustained pathway suppression rather than a short-lived pharmacologic dip. The biology fits the clinical pattern: IL-5 signaling drives eosinophil maturation, survival, and trafficking, and disabling that axis should limit the inflammatory burden that fuels EGPA activity.
Steroid Withdrawal Trailed Behind Eosinophil Depletion
Oral glucocorticoid reduction improved steadily, but the steroid-sparing effect did not become uniform across the cohort. By weeks 49 to 52, 27 patients in the benralizumab/benralizumab arm and 16 in the mepolizumab/benralizumab arm had withdrawn from oral glucocorticoids, equal to 40.9% and 25.8%. By weeks 101 to 104, those figures rose to 29 patients in each group, or 43.9% and 43.5%. The median cumulative oral glucocorticoid dose during the first year of the extension was 950 mg in the benralizumab/benralizumab group and 791 mg in the mepolizumab/benralizumab group.
The steroid data carry a familiar rheumatology message. Even when biologic therapy controls vasculitic inflammation, tapering glucocorticoids in EGPA remains constrained by residual airway disease, prior organ damage, clinician caution, and the need to avoid rebound flares. A low cumulative dose still matters because long-term glucocorticoid toxicity accumulates quickly in patients who often already carry cardiovascular, metabolic, and bone health risk from chronic inflammatory disease. For many patients, the question is not whether steroids can be reduced, but how far and how quickly they can be withdrawn without inviting relapse.
Eosinophil suppression was more complete with benralizumab. Median blood eosinophil counts in patients who remained on benralizumab were 20 cells/µL at weeks 52 and 100. In the group that switched from mepolizumab to benralizumab, the median count fell from 70 cells/µL to 20 cells/µL just 4 weeks after the switch. That rapid drop is biologically coherent: benralizumab targets the IL-5 receptor and is known for near-complete eosinophil depletion, whereas mepolizumab neutralizes IL-5 itself. In EGPA, where eosinophils are not a bystander signal but a central effector cell, the difference can translate into tighter suppression of the disease pathway.
The eosinophil response also explains why the switch arm moved quickly toward the same biomarker floor as the continuous benralizumab arm. A 4-week shift from 70 to 20 cells/µL is not merely a lab change; it suggests the inflammatory substrate is being stripped away fast enough to support steroid tapering and preserve remission in at least part of the cohort.
Safety Signals Stayed Consistent Across Both Treatment Sequences
Adverse events were common, as expected in a chronic multicenter vasculitis study with prolonged follow-up. They occurred in 97.0% of patients on benralizumab/benralizumab and 100% of those on mepolizumab/benralizumab. Serious adverse events were reported in 22.7% and 35.5% of those groups, respectively. The extension data do not signal a new safety concern, but they do remind clinicians that long-term EGPA management occurs in patients who remain medically complex even when the biologic strategy is working.
These safety numbers should be read alongside the disease itself. EGPA often involves older adults with asthma, sinus disease, prior steroid exposure, and systemic inflammation, so background event rates are rarely trivial. A biologic that controls eosinophilic activity without introducing an obvious late toxicity burden is clinically meaningful, especially when the alternative is continued glucocorticoid dependence. The extension therefore supports a treatment strategy centered on sustained eosinophil pathway inhibition rather than repeated steroid rescue.
The overall message from the 2-year dataset is straightforward: anti-IL-5/R therapy maintained remission in many patients, kept relapse rates relatively low, depleted eosinophils to low levels, and allowed meaningful steroid reduction. Switching from mepolizumab to benralizumab produced deeper eosinophil suppression and improved the steroid-sparing profile without a clear new safety penalty. For EGPA, where treatment decisions often hinge on balancing disease control against cumulative steroid harm, the extension provides a longer view of what sustained pathway blockade can achieve—and where tapering still stalls before full glucocorticoid withdrawal becomes routine.