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Practitioner's Corner

J Investig Allergol Clin Immunol 2019; Vol. 29(5): 378-398

© 2019 Esmon Publicidad

Mepolizumab for the Treatment of Eosinophilic

Granulomatosis With Polyangiitis: Our Experience

Díaz-Campos RM


*, Prudencio-Ribera VC


*, García-

Moguel I


, Fernández-Rodríguez C


, Corral-Blanco M


, Jarrin-

Estupiñan ME


, Melero-Moreno C



Severe Asthma Unit. Pneumology Service, Hospital Universitario

12 de Octubre, Madrid, Spain


Severe Asthma Unit. Allergology Service, Hospital Universitario

12 de Octubre, Madrid, Spain


Institute for Health Research (i+12), Hospital Universitario 12

de Octubre, Madrid, Spain


These authors contributed equally to this manuscript.

J Investig Allergol Clin Immunol 2019; Vol. 29(5): 384-385

doi: 10.18176/jiaci.0407

Key words:

Asthma. Vasculitis. Eosinophilia. IL-5. Mepolizumab.

Palabras clave:

Asma. Vasculitis. Eosinofilia. IL-5. Mepolizumab.

Eosinophilic granulomatosis with polyangiitis (EGPA) is

considered a hybrid condition comprising a hypereosinophilic

disorder and systemic antineutrophil cytoplasmic antibody

(ANCA)–associated vasculitis. It is characterized by the

presence of asthma, eosinophilia, multiorgan involvement,

and, sometimes, serum ANCA [1]. Its incidence has been

reported to be 0.5 to 6.8 new cases per million habitants in

the asthmatic population [2].

Systemic corticosteroids are the first-line treatment

for EGPA. As their short- and long-term consequences are

well-known, therapy is generally with corticosteroid-sparing

immunomodulators, such as methotrexate or azathioprine [3].

Advances in knowledge of the pathophysiology of

EGPA have led to a range of new treatments, such as

omalizumab, which enables corticosteroids to be spared.

However, reducing the dose of corticosteroids can increase

the risk of severe EGPA flares [4]. Mepolizumab is an

anti–interleukin-5 (IL-5) monoclonal antibody that reduces

the absolute eosinophil count with clinical improvement in

patients with other eosinophilic disorders, such as severe

eosinophilic asthma [5].

Since the serum IL-5 level is increased in EGPA, targeted

therapy against this cytokine has proven to be an effective


Mepolizumab has been used successfully in patients

with relapsing or refractory EGPA at an intravenous dose

of 750 mg once every 4 to 6 weeks [6,7]. In a multicenter

phase 3 study, Wechsler et al [8] administered mepolizumab

subcutaneously at 300 mg every 4 weeks and compared it with

placebo in 126 patients [8]. Since mepolizumab led to more

accrued weeks of remission than placebo, corticosteroid use

could thus be reduced. Furthermore, the time to first relapse

was longer with mepolizumab, and the exacerbation rate was

significantly lower during the treatment period than during

the nontreatment period. However, manifestations of EGPA

recurred on discontinuation [6-8]. A systematic review of the

results of these 3 studies was published in 2019 [9].

A recent post hoc analysis investigated the clinical benefit

of mepolizumab in patients with relapsing or refractory

EGPA and found that compared with the previous trial [8],

significantly more patients experienced remission or a ≥50%

reduction in corticosteroid dose or were relapse-free with

mepolizumab, mainly in specific subgroups (blood eosinophil

count ˂150/µL and weight >85 kg) [10].

We report 2 patients with corticosteroid-refractory

EGPA treated successfully with 300 mg of subcutaneous

mepolizumab every 4 weeks, according to the 2017 United

States Food and Drug Administration recommendation for

adult EGPA treatment.

A 43-year-old nonsmoking woman with a history of

allergic asthma, positive prick test results for dog epithelium

and house dust mite (

Dermatophagoides pteronyssinus,

Dermatophagoides farinae, Lepidoglyphus destructor, Blomia


), rhinosinusitis, and chronic suppurative otitis media

presented multiple mononeuritis, erythematous skin lesions

compatible with biopsy-proven vasculitis, and bilateral, patchy,

ground glass opacities with an upper lung distribution in a

chest computed tomography (CT) scan. Blood tests revealed

a positiveANCA titer, eosinophilia (37%), increased IgE level

(234 IU/mL), and a normal C-reactive protein level (CRP,

0.76 mg/dL). The patient was initially treated with prednisone

0.5 mg/kg/d, followed by 6 cyclophosphamide pulses (750

mg each) and azathioprine in order to spare treatment with

corticosteroids. The lowest dose reached was 10 mg/d of

prednisone, because symptoms recurred when the dose

was reduced. Omalizumab was subsequently administered

for 1 year, although it was discontinued because of lack of

efficacy (frequent asthma exacerbations and episodes of

suppurative otitis media). Subcutaneous mepolizumab was

tried at 300 mg every 4 weeks. Before starting mepolizumab

(while the patient was receiving 10 mg/d of prednisone), the

laboratory values were as follows: eosinophil blood count,

13%; serum IgE level, 234 IU/mL; and CRP, 2.07 mg/dL. The

Birmingham Vasculitis Activity Score (BVAS) was ˃3, and



was 103%of predicted. Sixmonths later, the asthma and otic

symptoms had improved significantly, the Asthma Control Test

(ACT) score had increased 3 points (22 to 25), blood eosinophilia

and CRP had decreased (1.1% and 0.26 mg/dL, respectively),


Erythematous skin lesions in a patient with eosinophilic

granulomatosis with polyangiitis.