Long-term efficacy of mepolizumab on eosinophilic granulomatosis with polyangiitis: a retrospective study

Abstract

Aim: Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by eosinophilic inflammation. Patients with EGPA are treated with systemic glucocorticoids and immunosuppressive drugs to induce and maintain remission. However, most patients relapse after tapering glucocorticoids, and there are refractory cases with inadequate response to glucocorticoids. Mepolizumab, a humanized anti-IL-5 antibody, is approved for relapsing or refractory EGPA. Furthermore, recent studies have reported the efficacy of benralizumab, a humanized anti-IL-5 receptor α antibody, in EGPA. Here, we investigate the efficacy of biologics on consecutive cases of EGPA. Methods: We retrospectively collected patients with EGPA treated with mepolizumab in addition to glucocorticoids at the Department of Pulmonary Medicine in Kagoshima University Hospital and Imakiire General Hospital. In this study, we compared the effects of biologics on inflammatory parameters between pre- and post-treatment of biologics in patients with EGPA. Results: Ten patients were included in the study. All patients were treated with mepolizumab, and one was switched to benralizumab later. Treatment with biologics markedly reduced EGPA relapse from 70% (pre-treatment) to 20% (post-treatment), Birmingham Vasculitis Activity Score from 8.4 to 4.0, peripheral blood eosinophil counts from 470.3 /µL to 40.5 /µL, and glucocorticoid doses from 7.3 mg/dL to 1.6 mg/dL. In contrast, lung function and fractional exhaled nitric oxide levels were not affected by treatment with biologics. Furthermore, the duration of biologics was positively correlated with symptom improvement. Conclusions: Treatment with mepolizumab for EGPA was effective in glucocorticoid sparing, symptom reduction, and relapse prevention. Mepolizumab is expected to reduce the risk of glucocorticoid-related adverse events. Therefore, continued administration as well as early intervention with mepolizumab for EGPA might be important to conserve future medical resources and control the disease.

Keywords

Asthma / benralizumab / biologic agent / eosinophilic granulomatosis with polyangiitis / glucocorticoid / mepolizumab

References

[1] Fogo AB, Cohen AH, Colvin RB, Jennette JC, Alpers CE. Crescentic Glomerulonephritis and Vasculitis. In: Fogo AB, Cohen AH, Colvin RB, Jennette JC, Alpers CE, editors. Fundamentals of Renal Pathology. Berlin, Heidelberg: Springer; 2014. pp. 107-22.

[2] White J, Dubey S. Eosinophilic granulomatosis with polyangiitis: A review. Autoimmun Rev. 2023; 22: 103219.

[3] Fijolek J, Radzikowska E. Eosinophilic granulomatosis with polyangiitis - Advances in pathogenesis, diagnosis, and treatment. Front Med (Lausanne). 2023; 10: 1145257.

[4] 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: 378-93.

[5] Wechsler ME, Akuthota P, Jayne D, Khoury P, Klion A, Langford CA, et al. ; EGPA Mepolizumab Study Team. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2017; 376: 1921-32.

[6] Guntur VP, Manka LA, Denson JL, Dunn RM, Dollin YT, Gill M, et al. Benralizumab as a Steroid-Sparing Treatment Option in Eosinophilic Granulomatosis with Polyangiitis. J Allergy Clin Immunol Pract. 2021; 9: 1186-93.e1.

[7] Nolasco S, Portacci A, Campisi R, Buonamico E, Pelaia C, Benfante A, et al. Effectiveness and safety of anti-IL-5/Rα biologics in eosinophilic granulomatosis with polyangiitis: a two-year multicenter observational study. Front Immunol. 2023; 14: 1204444.

[8] Sada KE, Kojo Y, Fairburn-Beech J, Sato K, Akiyama S, Van Dyke MK, et al. The prevalence, burden of disease, and healthcare utilization of patients with eosinophilic granulomatosis with polyangiitis in Japan: a retrospective, descriptive cohort claims database study. Mod Rheumatol. 2022; 32: 380-6.

[9] Mukhtyar C, Lee R, Brown D, Carruthers D, Dasgupta B, Dubey S, et al. Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann Rheum Dis. 2009; 68: 1827-32.

[10] Kitamura N, Hamaguchi M, Nishihara M, Ikumi N, Sugiyama K, Nagasawa Y, et al. The effects of mepolizumab on peripheral circulation and neurological symptoms in eosinophilic granulomatosis with polyangiitis (EGPA) patients. Allergol Int. 2021; 70: 148-9.

[11] Ueno M, Miyagawa I, Nakano K, Iwata S, Hanami K, Fukuyo S, et al. Effectiveness and safety of mepolizumab in combination with corticosteroids in patients with eosinophilic granulomatosis with polyangiitis. Arthritis Res Ther. 2021; 23: 86.

[12] Canzian A, Venhoff N, Urban ML, Sartorelli S, Ruppert AM, Groh M, et al. ; French Vasculitis Study Group and the European EGPA Study Group. Use of Biologics to Treat Relapsing and/or Refractory Eosinophilic Granulomatosis With Polyangiitis: Data From a European Collaborative Study. Arthritis Rheumatol. 2021; 73: 498-503.

[13] Ríos-Garcés R, Prieto-González S, Hernández-Rodríguez J, Arismendi E, Alobid I, Penatti AE, et al. Response to mepolizumab according to disease manifestations in patients with eosinophilic granulomatosis with polyangiitis. Eur J Intern Med. 2022; 95: 61-6.

[14] Nakamura Y, Fukutomi Y, Sekiya K, Kajiwara K, Kawasaki Y, Fujita N, et al. Low-dose mepolizumab is effective as an add-on therapy for treating long-lasting peripheral neuropathy in patients with eosinophilic granulomatosis with polyangiitis. Mod Rheumatol. 2022; 32: 387-95.

[15] Bettiol A, Urban ML, Dagna L, Cottin V, Franceschini F, Del Giacco S, et al. ; European EGPA Study Group. Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study. Arthritis Rheumatol. 2022; 74: 295-306.

[16] Özdel Öztürk B, Yavuz Z, Aydın Ö, Mungan D, Sin BA, Demirel YS, et al. Effectiveness of Low-Dose Mepolizumab in the Treatment of Eosinophilic Granulomatosis with Polyangiitis (EGPA): A Real-Life Experience. Int Arch Allergy Immunol. 2022; 183: 1281-90.

[17] Yamane T, Hashiramoto A. Mepolizumab exerts crucial effects on glucocorticoid discontinuation in patients with eosinophilic granulomatosis with polyangiitis: a retrospective study of 27 cases at a single center in Japan. Arthritis Res Ther. 2023; 25: 110.

[18] Matsuno O. Factors Affecting the Ability to Discontinue Oral Corticosteroid Use in Patients with EGPA Treated with Anti-Interleukin-5 Therapy. Int Arch Allergy Immunol. 2024; 185: 116-23.

[19] Ishii T, Kunishige H, Kobayashi T, Hayashi E, Komatsubara M, Ishii T, et al. Real-world safety and effectiveness of mepolizumab for patients with eosinophilic granulomatosis with polyangiitis (EGPA) in Japan: A 48-week interim analysis of the MARS study. Mod Rheumatol. 2024; 34: 978-87.

[20] Cottu A, Groh M, Desaintjean C, Marchand-Adam S, Guillevin L, Puechal X, et al. ; French Vasculitis Study Group. Benralizumab for eosinophilic granulomatosis with polyangiitis. Ann Rheum Dis. 2023; 82: 1580-6.

[21] Bettiol A, Urban ML, Padoan R, Groh M, Lopalco G, Egan A, et al. ; European EGPA Study Group. Benralizumab for eosinophilic granulomatosis with polyangiitis: a retrospective, multicentre, cohort study. Lancet Rheumatol. 2023; 5: e707-15.

[22] Nanzer AM, Maynard-Paquette AC, Alam V, Green L, Thomson L, Lam J, et al. Long-Term Effectiveness of Benralizumab in Eosinophilic Granulomatosis With Polyangiitis. J Allergy Clin Immunol Pract. 2024; 12: 724-32.

[23] Wechsler ME, Nair P, Terrier B, Walz B, Bourdin A, Jayne DRW, et al. ; MANDARA Study Group. Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2024; 390: 911-21.

[24] Painter MW, Brosius Lutz A, Cheng YC, Latremoliere A, Duong K, Miller CM, et al. Diminished Schwann cell repair responses underlie age-associated impaired axonal regeneration. Neuron. 2014; 83: 331-43.

[25] Nocera G, Jacob C. Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury. Cell Mol Life Sci. 2020; 77: 3977-89.

[26] Khatri S, Moore W, Gibson PG, Leigh R, Bourdin A, Maspero J, et al. Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2019; 143: 1742-51.e7.

[27] Korn S, Bourdin A, Chupp G, Cosio BG, Arbetter D, Shah M, et al. Integrated Safety and Efficacy Among Patients Receiving Benralizumab for Up to 5 Years. J Allergy Clin Immunol Pract. 2021; 9: 4381-92.e4.

[28] Hellmich B, Csernok E, Gross WL. Proinflammatory cytokines and autoimmunity in Churg-Strauss syndrome. Ann N Y Acad Sci. 2005; 1051: 121-31.

[29] Jakiela B, Szczeklik W, Plutecka H, Sokolowska B, Mastalerz L, Sanak M, et al. Increased production of IL-5 and dominant Th2-type response in airways of Churg-Strauss syndrome patients. Rheumatology (Oxford). 2012; 51: 1887-93.

[30] Biedroń G, Włudarczyk A, Wawrzycka-Adamczyk K, Wójcik K, Sznajd J, Zdrojewski Z, et al. Treatment and its side effects in ANCA-associated vasculitides - Study based on POLVAS registry data. Adv Med Sci. 2020; 65: 156-62.

[31] Global Initiative for Asthma [Internet]. Bethesda: GINA; c2023 [cited 2024 Mar 7]. Global strategy for asthma management and prevention 2023. Available from: http://ginasthma.org

[32] Durel CA, Berthiller J, Caboni S, Jayne D, Ninet J, Hot A. Long-Term Followup of a Multicenter Cohort of 101 Patients With Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss). Arthritis Care Res (Hoboken). 2016; 68: 374-87.