POS0337 MEPOLIZUMAB VERSUS BENRALIZUMAB FOR EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA): A EUROPEAN REAL-LIFE RETROSPECTIVE COMPARATIVE STUDY
Authors: I. Mattioli, A. Bettiol, V. Cottin, A. Egan, F. Franceschini, M. Groh, D.R.W. Jayne, G. Lopalco, T. Neumann, R. Padoan, J. Schroeder, A. Vaglio, G. Emmi
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterised by asthma, ear-nose-throat (ENT) involvement, and systemic vasculitic manifestations. [1] Interleukin (IL)-5 inhibitors are currently used for EGPA treatment, controlling both respiratory and systemic manifestations. [2-5] <h3>Objectives:</h3> This study aimed to compare the efficacy and safety of the anti-IL5 drug mepolizumab to the IL-5 receptor antagonist benralizumab in a European cohort of patients with EGPA. <h3>Methods:</h3> A retrospective observational cohort study was conducted on EGPA patients treated with mepolizumab or benralizumab at the dosage approved for eosinophilic asthma at 47 centers belonging to the European EGPA Study Group. Patients in the benralizumab group were matched 1:1 to those in the mepolizumab one, by sex, age (± 5 years), Birmingham Vasculitis Activity Score (BVAS) (± 2) and oral corticosteroids (OCS) dosage (± 2.5mg/day) at time of treatment beginning (T0), and data were then compared after 3, 6, and 12 months. Complete response (CR) was defined as no disease activity (BVAS= 0) and OCS dose ≤4mg/day; OCS tapering was evaluated considering the ongoing dosage at each timepoint. Pulmonary function (variation in the forced expiratory volume in 1 second [FEV1] expressed as ΔFEV1) and safety outcomes were compared over a 12-month follow-up. <h3>Results:</h3> 88 EGPA patients treated with mepolizumab and 88 with benralizumab were matched according to a pre-defined set of baseline variables. Fifty patients in each group (57.0%) were female, with a median age at T0 of 54 years (IQR 23-45). Baseline characteristics at T0 is reported in <b>Figure 1</b>. CR remarkably increased during follow-up in both groups. At T3, CR was reported in 12/88 patients (13.6%, 95% CI 7.2-22.6%) in mepolizumab group and 9/88 patients (10.2%, 4.8-18.5%) in benralizumab cohort (p=0.485). At T6, the CR rates increased to 18/83 patients (21.7%, 13.4-32.1%) in the mepolizumab cohort and 21/66 (31.8%, 20.1-44.4%) respectively (p=0.128), reaching 22/68 (32.4%, 21.5-44.8%) and 25/52 (48.1%, 34.0-62.4%) at T12, respectively (p=0.005). Moreover, a reduction of BVAS was observed in both cohorts with no statistical differences at each timepoint. <b>(Figure 2</b>) A OCS-sparing effect was observed in both groups, the daily OCS dose decreasing from 10 mg/day (IQR 5– 12.5) to 5 mg/day (3-7.5) at T3, 5 mg/day (1.3-5) at T6, and 4 mg/day (0-4.5) at T12 in the mepolizumab cohort, and from 10 mg/day (7-13) to 5 mg/day (5-8) at T3, 5 mg/day (2-5) at T6, and 2.5 mg/day (0-5) at T12 in the benralizumab cohort. No differences were observed when comparing the daily OCS dosage between the two groups at T3 (p=0.467), T6 (p=0.823) and T12 (p=0.115). <b>(Figure 2</b>) Under treatment with mepolizumab, 5 patients relapsed after achieving CR: 2 relapses occurred at T6 and 3 at T12; under treatment with benralizumab, 4 patients relapsed after achieving CR at T12. Compared to baseline values, an improvement in FEV1 was observed in both cohort with no statistically significant differences between the two groups [from T0 to T3: +6.6% (IQR2-17.5) for mepolizumab vs +13.7% (4.4-22.1) for benralizumab (p=0.039); from T0 to T6: +12.0% (2.1-16.5) vs +14.7% (7.73-29.3) (p=0.669); from T0 to T12: +10.6% (4.7-25.9) vs +13.2% (0.1-43.9) (p=0.267)]. Concerning the safety profile, 11 patients (12.5%) reported adverse events during treatment with mepolizumab and 15 (17.0%) with benralizumab. Most events were mild, with only one on mepolizumab and 2 on benralizumab requiring hospitalization. Finally, 9/88 (10%) patients discontinued mepolizumab and 16/88 (18%) discontinued benralizumab (p= 0.130). <h3>Conclusion:</h3> These results suggest that mepolizumab and benralizumab at the dosage approved for eosinophilic asthma showed comparable effectiveness in controlling systemic and respiratory involvement, and both treatments were associated with a good safety profile. <h3>REFERENCES:</h3> [1] Fagni <i>Front Med</i> 2021. [2] Bettiol <i>Arthritis Rheumatol (Hoboken, NJ</i>) 2022. [3] Bettiol <i>Ann Rheum Dis</i> 2022. [4] Cottu <i>Ann Rheum Dis</i> 2023. [5] Bettiol <i>Lancet Rheumatol</i> 2023. <h3>Acknowledgements:</h3> EGPA Study Group. <h3>Disclosure of Interests:</h3> Irene Mattioli: None declared, Alessandra Bettiol: None declared, Vincent Cottin GSK and AstraZeneca, GSK and AstraZeneca, GSK and AstraZeneca, Allyson Egan: None declared, Franco Franceschini: None declared, Matthieu Groh GSK and AstraZeneca, David R. W. Jayne Amgen, AZ, Aurinia, GSK, Novartis, Roche, Takeda, CSL-Vifor, Amgen, AZ, Aurinia, GSK, Novartis, Roche, Takeda, CSL-Vifor, Giuseppe Lopalco: None declared, Thomas Neumann: None declared, Roberto Padoan GSK, GSK, Jan Schroeder: None declared, Augusto Vaglio GSK and AstraZeneca, GSK and AstraZeneca, Giacomo Emmi GSK and AstraZeneca, GSK and AstraZeneca.