Early Mepolizumab Plus Glucocorticoids in Newly Diagnosed Eosinophilic Granulomatosis With Polyangiitis: A 52-Week Multicenter Retrospective Cohort Study

Autores articulo: Boira I, Rodríguez-Melean N, De Las Vecillas L, Romero D, Noblejas A, Trisán A, et al. Early Mepolizumab Plus Glucocorticoids in Newly Diagnosed Eosinophilic Granulomatosis With Polyangiitis: A 52-Week Multicenter Retrospective Cohort Study. Arch Bronconeumol. 2026:S0300-2896(26)00286-3. doi: 10.1016/j.arbres.2026.07.012.

Autor del comentario: Ignacio Boira. Servicio de Neumologia Hospital Sant Joan de Alicante

Palabras clave: anti-IL5, GEPA, terapia inducción, mepolizumab

Comentario:

Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic autoantibody vasculitis (ANCA), of uncertain etiology, characterized by eosinophil-rich necrotizing granulomatous inflammation together with necrotizing vasculitis of small and medium arteries.

The estimated prevalence in Europe is 12 cases/million inhabitants, but the condition is likely underdiagnosed due to symptomatic overlap with other pathologies.

It was first described in 1951 by Jacob Churg and Lotte Strauss as a cluster of symptoms including asthma or fever, eosinophilia and vasculitis in various organs. Later, in 1990, the American College of Rheumatology (ACR) defined several diagnostic criteria, which were replaced by the criteria established at the International Chapel Hill Consensus Conference (presence of eosinophil-rich granulomatous inflammation, necrotizing vasculitis of small and medium vessels, asthma, and eosinophilia). The current diagnostic and therapeutic recommendations are those of the ACR/European League Against Rheumatism (EULAR)in 2022 (obstructive pulmonary disease, nasal polyposis, multiple mononeuritis, eosinophilia >1000 cells/µL, and predominantly eosinophilic extravascular inflammation on biopsy).

EGPA evolves through different phases: prodromal period (mainly late-onset asthma and other allergic symptoms), eosinophilic phase (blood and tissue eosinophilia), and finally, small vessel vasculitis. However, this progression does not occur in all patients, and the different phases may overlap.

Clinically, the most common manifestation is asthma in 90-100% of patients. Pulmonary infiltrates manifest in 30-70% of patients and are transient, with a favourable response to corticosteroids. The prevalence of upper airway involvement, manifesting as polyposis or allergic rhinitis, ranges from 50 to 90% among patient populations. Among the neurological manifestations, the most common is multiple mononeuritis, which occurs in 46-75% of patients. At the cutaneous level, palpable purpura is present in 40-70% of patients. Gastrointestinal involvement is only present in 22-32% of patients, while cardiac, renal, and ocular involvement are exceptional.

The eosinophilic phase is characterized by greater pulmonary, cardiac, and gastrointestinal involvement; while in the vasculitic phase, there is greater neuropathic, renal, and dermal involvement.

EGPA pathophysiology involves activation mainly of the TH2 pathway, leading to eosinophil (mediated mainly by interleukin [IL]-5 and induced by eotaxin-3 chemotaxis) and B cell activation (IL-4, IL-5 and IL-13 mediated), but also of the Th1/Th17 pathway, with neutrophil activation, granulomatosis and vascular damage.

In this context, IL-5 is a cytokine that plays an essential role in the pathogenesis of EGPA by promoting the proliferation, activation, and survival of eosinophils (6). There are currently two biological treatments indicated for the treatment of EGPA. Mepolizumab is a humanized monoclonal antibody (IgG1, kappa) that acts by blocking the binding of IL-5 to the alpha chain of the IL-5 receptor expressed on the eosinophil surface (7) and benralizumab is a humanized, afucosylated monoclonal antibody (IgG1, kappa) that acts by directly binding to the alpha subunit of the IL-5 receptor (IL-5Rα) expressed on the surface of eosinophils and basophils, blocking its interaction with IL-5 and inducing direct cell apoptosis via antibody-dependent cellular cytotoxicity (8).

Biological treatments are recommended in maintenance of remission and the induction of remission in patients with relapsing or refractory EGPA without active organ-threatening or lifethreatening disease (9). Nevertheless, there is limited evidence regarding its efficacy as induction therapy in new-onset EGPA, both with/without organ-threatening or lifethreatening disease (10,11). This article has recently been published evaluating the efficacy of the combination of corticosteroids and mepolizumab as induction therapy in new-onset EGPA.

This multicenter, observational, retrospective cohort study evaluated adults with new-onset EGPA treated between 2021 and 2025 with mepolizumab 300 mg every 4 weeks in combination with systemic glucocorticoids (GCs) as induction therapy. Patients were followed for at least 52 weeks. Treatment decisions reflected routine clinical practice. Patients receiving cyclophosphamide or rituximab for induction, lower-dose mepolizumab, or treatment for relapsing/refractory EGPA were excluded. EGPA diagnosis was established through compatible clinical manifestations, objective evidence of vasculitic or eosinophilic organ involvement, exclusion of mimicking conditions, and multidisciplinary consensus. The primary outcomes were remission and GC dose reduction at weeks 24 and 52. Secondary outcomes included GC withdrawal, changes in FEV1, Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), asthma exacerbations, EGPA relapse, and peripheral eosinophil counts. Remission was defined as absence of systemic or inflammatory manifestations, no relapses, and a prednisone-equivalent dose ≤4 mg/day.

Twenty patients were included, 14 of whom had organ-threatening or lifethreatening disease, including alveolar haemorrhage (n=7), cardiac involvement (n=4), mononeuritis multiplex (n=2), and glomerulonephritis (n=1). Remission was achieved in 90% of patients at week 24 and 95% at week 52, without significant differences between patients with and without organ-threatening or lifethreatening disease. Median GC dosage decreased from 55 mg/day after hospital discharge to 5 mg/day at week 24 and 2.25 mg/day at week 52. Among patients achieving remission, GC withdrawal occurred in 30% at week 24 and 60% at week 52. Asthma exacerbations decreased significantly and FEV1, ACT, and AQLQ scores improved significantly at both follow-up time points. Peripheral eosinophil counts also decreased substantially. Only one relapse occurred after initiation of mepolizumab, and no serious adverse events, major infections, or treatment discontinuations attributable to mepolizumab were reported.

The main limitations were the retrospective design, small sample size, lack of a control group, potential selection bias, and limited power for subgroup analyses.
These factors preclude causal conclusions and highlight the need for prospective controlled trials to define the optimal use of early IL-5 blockade in newly diagnosed EGPA.

Therefore, early administration of mepolizumab 300 mg every 4 weeks, combined with systemic GCs, was associated with high remission rates, substantial GC sparing, improved pulmonary and asthma-related outcomes, and a low relapse rate over 52 weeks in this cohort of newly diagnosed EGPA. Notably, these outcomes were observed despite the inclusion of patients with or without organ-threatening or lifethreatening disease. The results support the hypothesis that eosinophilic inflammation may represent a major therapeutic target in selected patients with severe EGPA and suggest that early IL-5 blockade requires further investigation as an induction strategy.

Bibliografia:

1. White J, Dubey S. Eosinophilic granulomatosis with polyangiitis: A review. Autoimmun Rev. 2023;22(1):103219. doi: 10.1016/j.autrev.2022.103219.
2. Romero Gómez C, Hernández Negrín H, Ayala Gutiérrez MDM. Eosinophilic granulomatosis with polyangiitis. Med Clin (Barc). 2023;160(7):310-317. doi: 10.1016/j.medcli.2023.01.003.
3. Emmi G, Bettiol A, Gelain E, Bajema IM, Berti A, Burns S, et al. Evidence-Based Guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis. Nat Rev Rheumatol. 2023;19(6):378-393. doi: 10.1038/s41584-023-00958-w. 
4. Watanabe R, Hashimoto M. Eosinophilic Granulomatosis with Polyangiitis: Latest Findings and Updated Treatment Recommendations. J Clin Med. 2023 Sep 15;12(18):5996. doi: 10.3390/jcm12185996.
5. López Paraja M, Starita Fajardo G, Donate Velasco I, Lucena López D, Iranzo Alcolea MP, Lirola Sánchez FJ, et al. Molecular Pathogenesis and Targeted Therapies in Eosinophilic Granulomatosis with Polyangiitis: An Updated Review. Int J Mol Sci. 2025;26(22):11141. doi: 10.3390/ijms262211141.
6. Shiomi M, Watanabe R, Ishihara R, Tanaka S, Nakazawa T, Hashimoto M. Comparative Insights on IL-5 Targeting with Mepolizumab and Benralizumab: Enhancing EGPA Treatment Strategies. Biomolecules. 2025;15(4):544. doi: 10.3390/biom15040544.
7. Wechsler ME, Silver J, Wolff G, Price RG, Verghis R, Weller PF, et al. Long-Term Safety and Efficacy of Mepolizumab in Eosinophilic Granulomatosis With Polyangiitis. Arthritis Rheumatol. 2025;77(8):1052-1062. doi: 10.1002/art.43146. 
8. Wechsler ME, Nair P, Terrier B, Walz B, Bourdin A, Jayne DRW, et al. Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2024 390(10):911-921. doi: 10.1056/NEJMoa2311155. 
9.  Hellmich B, Sanchez-Alamo B, Schirmer JH, Berti A, Blockmans D, Cid MC, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024;83(1):30-47. doi: 10.1136/ard-2022-223764.
10. Chacín Y, Boira I, Chiner E. Induction therapy with mepolizumab for cardiac involvement in eosinophilic granulomatosis with polyangiitis. Med Clin (Barc). 2025;165(2):107030. doi: 10.1016/j.medcli.2025.107030.
11. Ueno M, Miyagawa I, Aritomi T, Kimura K, Iwata S, Hanami K, et al. Safety and effectiveness of mepolizumab therapy in remission induction therapy for eosinophilic granulomatosis with polyangiitis: a retrospective study. Arthritis Res Ther. 2022;24(1):159. doi: 10.1186/s13075-022-02845-3.