Successful treatment with benralizumab in a patient with eosinophilic granulomatosis with polyangiitis refractory to mepolizumab

Francesco Menzella; Carla Galeone; Giulia Ghidoni; Patrizia Ruggiero; Silvia Capobelli; Anna Simonazzi; Chiara Catellani; Chiara Scelfo; Francesco Livrieri; Nicola Facciolongo

doi:10.4081/mrm.2021.779

Successful treatment with benralizumab in a patient with eosinophilic granulomatosis with polyangiitis refractory to mepolizumab

Authors

Francesco Menzella Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia IRCCS, Reggio Emilia https://orcid.org/0000-0003-3950-5789
Carla Galeone Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia IRCCS, Reggio Emilia
Giulia Ghidoni Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia IRCCS, Reggio Emilia
Patrizia Ruggiero Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia IRCCS, Reggio Emilia
Silvia Capobelli Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia IRCCS, Reggio Emilia
Anna Simonazzi Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia IRCCS, Reggio Emilia https://orcid.org/0000-0001-9825-3396
Chiara Catellani Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia IRCCS, Reggio Emilia https://orcid.org/0000-0003-0612-1746
Chiara Scelfo Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia IRCCS, Reggio Emilia https://orcid.org/0000-0002-3192-3882
Francesco Livrieri Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia IRCCS, Reggio Emilia
Nicola Facciolongo Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia IRCCS, Reggio Emilia

DOI: https://doi.org/10.4081/mrm.2021.779

Keywords:

Vasculitis, asthma, eosinophils, oral corticosteroids, biologics, IL-5

Abstract

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by necrotizing eosinophilic granulomatous inflammation that frequently involves the respiratory tract (90% of cases). Asthma in EGPA is systematically severe and often refractory to common treatment, it is corticosteroid resistant and can often anticipate the onset of systemic vasculitis by many years. A release of cytokines necessary for the activation, maturation and survival of eosinophils, such as IL-4, IL-5 and IL-13 occurs in the activated Th-2 phenotype. In particular, IL-5 level is high in active EGPA and its inhibition has become a key therapeutic target. Oral glucocorticoids (OCS) are effective treatment options but unfortunately, frequent relapses occur in many patients and they lead to frequent side effects. As for now, there are currently no official recommendations on doses and treatment schedules in the management of EGPA.
Case presentation: In this article, we describe the case of a man with EGPA, severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), with poor asthma and CRSwNP control despite OCS and mepolizumab treatment. Respiratory and vasculitis symptoms improved markedly after therapeutic switch to benralizumab. During the treatment, in addition to clinical effects, we witnessed a depletion of blood eosinophils, as well as an improvement in both pulmonary function tests, CT scan and skin lesions present initially.
Conclusions: While there are many studies confirming the efficacy of benralizumab in EGPA, the most interesting aspect of our report is that efficacy was confirmed in a patient previously unresponsive to mepolizumab, known to be effective in EGPA.

References

Jennette JC, Falk RJ, Bacon PA, asu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013;65:1–11.

Cordier JF, Cottin V, Guillevin L, Bel E, Bottero P, Dalhoff K, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Presse Med 2013;42:507–10.

Cottin V, Cordier JF. Eosinophilic pneumonia. In: Mason RJ, Ernst JD, King TE Jr, et al., editors. Murray and Nadel’s Textbook of Respiratory Medicine. 6th Ed. Philadelphia, Elsevier Saunders, 2016; p. 1221–42.

Mahr A, Moosig F, Neumann T, Szczeklik W, Taillé C, Vaglio A, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): evolutions in classification, etiopathogenesis, assessment and management. Curr Opin Rheumatol 2014;26:16–23.

Tsurikisawa N, Tsuburai T, Saito H, Morita S, Horiguchi Y, Mitomi H, et al. A retrospective study of bronchial hyperresponsiveness in patients with asthma before the onset of Churg-Strauss syndrome. Allergy Asthma Proc 2007;28:336–43.

Lanham JG, Elkon KB, Pusey CD, Hughes GR. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome. Medicine (Baltimore) 1984;63:65–81.

Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, Casassus P. Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore) 1999;78:26–37.

Kiene M, Csernok E, Müller A, Metzler C, Trabandt A, Gross WL. Elevated interleukin-4 and interleukin-13 production by T cell lines from patients with Churg-Strauss syndrome. Arthritis Rheum 2001;44:469–73.

Dunogué B, Pagnoux C, Guillevin L. Churg-strauss syndrome: clinical symptoms, complementary investigations, prognosis and outcome, and reatment. Semin Respir Crit Care Med 2011;32:298–309.

Falk RJ, Terrell RS, Charles LA, Jennette JC. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci USA 1990;87:4115–9.

Xiao H, Heeringa P, Hu P, Liu Z, Zhao M, Aratani Y, et al. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest 2002;110:955–63.

Jakiela B, Sanak M, Szczeklik W, Sokolowska B, Plutecka H, Mastalerz L, et al. Both Th2 and Th17 responses are involved in the pathogenesis of Churg-Strauss syndrome. Clin Exp Rheumatol 2011;29:S23-34.

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 2012;51:1887–93.

Moosig F, Gross WL, Herrmann K, Bremer JP, Hellmich B. Targeting interleukin-5 in refractory and relapsing Churg-Strauss syndrome. Ann Intern Med 2011;155:341–3.

Terrier B, Bièche I, Maisonobe T, Laurendeau I, Rosenzwajg M, Kahn JE, et al. Interleukin-25: a cytokine linking eosinophils and adaptive immunity in Churg-Strauss syndrome. Blood 2010;116:4523–31.

Vaglio A, Moosig F, Zwerina J. Churg-Strauss syndrome: update on pathophysiology and treatment. Curr Opin Rheumatol 2012;24:24–30.

Mahr A, Guillevin L, Poissonnet M, Aymé S. Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener’s granulomatosis, and Churg-Strauss syndrome in a French urban multiethnic population in 2000: A capture-recapture estimate. Arthritis Care Res 2004;51:92–9.

Watts RA, Lane SE, Bentham G, Scott DG. Epidemiology of systemic vasculitis: a ten-year study in the United Kingdom. Arthritis Rheum 2000;43:414–9.

Ramentol-Sintas M, Martínez-Valle F, Solans-Laqué R. Churg-Strauss Syndrome: an evolving paradigm. Autoimmun Rev 2012;12:235–40.

Zwerina J, Bach C, Martorana D, Jatzwauk M, Hegasy G, Moosig F, et al. Eotaxin-3 in Churg-Strauss syndrome: a clinical and immunogenetic study. Rheumatology 2011;50:1823–7.

Churg A. Recent advances in the diagnosis of Churg-Strauss syndrome. Mod Pathol 2001;14:1284–93.

Fulkerson PC, Rothenberg ME. Targeting eosinophils in allergy, inflammation and beyond. Nat Rev Drug Discov 2013;12:117-29.

Comarmond C, Pagnoux C, Khellaf M, Cordier JF, Hamidou M, Viallard JF, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term follow-up of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum 2013;65:270-81.

Samson M, Puechal X, Devilliers H, Ribi C, Cohen P, Stern M, et al. Long-term outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) enrolled in two prospective trials. J Autoimmun 2013;43:60-9.

Daugherty J, Lin X, Baxter R, Suruki R, Bradford E. The impact of long-term systemic glucocorticoid use in severe asthma: a UK retrospective cohort analysis. J Asthma 2018;55:651-8.

Strehl C, Bijlsma JW, de Wit M, Boers M, Caeyers N, Cutolo M, et al. Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann Rheum Dis 2016;75:952-7.

Groh M, Pagnoux C, Baldini C, Bel E, Bottero P, Cottin V, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) Consensus Task Force recommendations for evaluation and management. Eur J Intern Med 2015;26:545-53.

Puechal X, Pagnoux C, Baron G, Quémeneur T, Néel A, Agard C, et al. Adding azathioprine to remission-induction glucocorticoids for eosinophilic granulomatosis with polyangiitis (Churg-Strauss), microscopic polyangiitis, or polyarteritis nodosa without poor prognosis factors: a randomized, controlled trial. Arthritis Rheumatol 2017;69:2175-86.

Wechsler ME, Akuthota P, Jayne D, Khoury P, Klion A, Langford CA, et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med 2017;376:1921-32.

U.S. Food and Drug Administration. Nucala prescribing information. Accessed: January 1, 2021. Available from: www.accessdata.fda.gov

Caminati M, Crisafulli E, Lunardi C, Micheletto C, Festi G, Maule M, et al. Mepolizumab 100 mg in severe asthmatic patients with EGPA in remission phase. J Allergy Clin Immunol Pract 2021;9:1386-8.

Vultaggio A, Nencini F, Bormioli S, Vivarelli E, Dies L, Rossi O, et al. Low-dose mepolizumab effectiveness in patients suffering from eosinophilic granulomatosis with polyangiitis. Allergy Asthma Immunol Res 2020;12:885-93.

Coppola A, Flores KR, De Filippis F. Rapid onset of effect of benralizumab on respiratory symptoms in a patient with eosinophilic granulomatosis with polyangiitis. Respir Med Case Rep 2020;30:101050.

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.

Miyata Y, Inoue H, Homma T, Tanaka A, Sagara H. Efficacy of benralizumab and clinical course of Igg4 on eosinophilic granulomatosis with polyangiitis. J Investig Allergol Clin Immunol 2020;0. Online ahead of print.

Nanzer AM, Dhariwal J, Kavanagh J, Hearn A, Fernandes M, Thomson L, et al. Steroid-sparing effects of benralizumab in patients with eosinophilic granulomatosis with polyangiitis. ERJ Open Res 2020;6:00451-2020.

Padoan R, Chieco Bianchi F, Marchi MR, Cazzador D, Felicetti M, Emanuelli E, et al. Benralizumab as a glucocorticoid-sparing treatment option for severe asthma in eosinophilic granulomatosis with polyangiitis. J Allergy Clin Immunol Pract 2020;8:3225-7.

Samson M, Puéchal X, Devilliers H, Ribi C, Cohen P, Bienvenu B, et al. Mononeuritis multiplex predicts the need for immunosuppressive or immunomodulatory drugs for EGPA, PAN and MPA patients without poor prognosis factors. Autoimmun Rev 2014;13:945-53.

Martínez-Rivera C, Garcia-Olivé I, Urrutia-Royo B, Basagaña-Torrento M, Rosell A, Abad J. Rapid effect of benralizumab in exacerbation of severe eosinophilic asthma associated with eosinophilic granulomatosis with polyangiitis. BMC Pulm Med 2021;21:35.

Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012;380:651–9.

Ortega HG, Liu MC, Pavord ID, russelle GG, FitzGerald JM, Chetta A, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014;371:1198–207.

Vergles M, Matković Z, Lalić K, Trkanjec JT, Tudorić N. Mepolizumab as a glucocorticoid-sparing agent in eosinophilic granulomatosis with polyangiitis (EGPA): is a lower dose sufficient? J Asthma 2020;1-5. Online ahead of print.

Kahn JE, Grandpeix-Guyodo C, Marroun I, Marroun I, Catherinot E, Mellot F, et al. Sustained response to mepolizumab in refractory Churg-Strauss syndrome. J Allergy Clin Immunol 2010;125:267–70.

Kim S, Marigowda G, Oren E, Israel E, Wechsler ME. Mepolizumab as a steroid-sparing treatment option in patients with Churg-Strauss syndrome. J Allergy Clin Immunol 2010;125:1336–43.

Moosig F, Gross WL, Herrmann K, Bremer JP, Hellmich B. Targeting interleukin-5 in refractory and relapsing Churg-Strauss syndrome. Ann Intern Med 2011;155:341–3.

Herrmann K, Gross WL, Moosig F. Extended follow-up after stopping mepolizumab in relapsing/refractory Churg-Strauss syndrome. Clin Exp Rheumatol 2012;30:S62–5.

Menzella F, Biava M, Bagnasco D, Galeone C, Simonazzi A, Ruggiero P, et al. Efficacy and steroid-sparing effect of benralizumab: has it an advantage over its competitors? Drugs Context 2019;8:212580.

ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2019 Nov 8. Identifier NCT04157348, Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab. (MANDARA). Accessed 3 January 2021. Available from: https://www.clinicaltrials.gov/ct2/show/NCT04157348

ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2019 Nov 8. Identifier NCT03010436, Benralizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis (EGPA) Study (BITE). Accessed 3 January 2021. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03010436

Tan LE, Tan WHG, Aziz MIA, Aziz MIA, Koh MS, Tay TR, et al. Assessing the cost-effectiveness of mepolizumab as add-on therapy to standard of care for severe eosinophilic asthma in Singapore. J Asthma 2020;1-11. Online ahead of print.