D2.170 - Real-world effectiveness of anti-IL-5/IL-5Rα agents as induction therapy in eosinophilic granulomatosis with polyangiitis

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a necrotizing vasculitis of the small- to medium-sized blood vessels, in which eosinophilic dysregulation plays a crucial role in disease pathophysiology. Multisystem involvement is common, predominantly affecting the upper and lower airways, altough other organ manifestations may occur. Recent treatment guidelines for EGPA include biological therapies targeting interleukin-5 (IL-5), in addition to conventional management with systemic corticosteroids (SCS) and immunosuppressants. However, their role as induction therapy has not yet been explored extensively. 

We conducted a retrospective multicentre cohort study of patients with EGPA treated with mepolizumab (300mg/28 days) or benralizumab (30mg/28 days) as induction therapy. Patients receiving cyclophosphamide and/or rituximab for induction and/or relapsing/refractory EGPA were excluded. The primary outcomes were remission (absence of relapse and prednisone<5 mg/day) and SCS reduction at weeks 24 and 52.

Twenty patients received mepolizumab as initial treatment. 14 had organ-threatening involvement (alveolar haemorrhage 7, cardiac 4, mononeuritis multiplex 2, glomerulonephritis 1). Remission was achieved in 90% at week 24 and 95% at week 52; among those in remission, GCs were stopped in 30% and 55%, respectively. SCS (prednisone-equivalent) were reduced from a median dose at discharge of 55 mg/day (IQR 40-70), to 5 mg at week 24 and 2.25 mg at week 52 (p<=0.002). At week 52, 33% of patients were unable to discontinue oral SCS due to adrenal insufficiency. FEV1 improved 156mL at week 24 and 364mL at week 52 and exacerbations decreased to 3.2 to 0.15 and 0.55 (all p<=0.03). ACT and AQLQ improved 5 points and 1.5 respectively.

One patient was initially treated with benralizumab after diagnosis of EGPA, with organ-threatening involvement (alveolar haemorrhage, venous thrombosis, constitutional and síndrome and elevation of cardiac biomarkers without structural heart disease). After 24 weeks of treatment, FEV1 improved 230mL and prednisone treatment was successfully tapered from 30 mg/day to complete discontinuation with no exacerbations.

Anti-IL5/IL5Ra as induction treatment in EGPA may represent an effective therapeutic alternative to conventional immunosuppressive therapy, allowing high remission rates, meaningful SCS-sparing, and improved asthma control.