TABLE 4

Summary of trials investigating the use of anti-IgE and anti-IL-5/5R monoclonal antibodies in EGPA

Name of biologic and targetFirst author [ref.], yearStudy typeNumber of patients,
other immunosuppresants
Remission or response definition
and end-points
Results
Rituximab, anti-CD20Teixeira [66], 2019Retrospective cohort study69 patients; other immunosuppressants allowed but not specifiedVasculitic end-point:
BVAS of 0 with <5 mg·day−1 of oral glucocorticoid
58% of patients achieved remission with 7% being in remission with no corticosteroid need. 54% of patients relapsed by 24 months. ANCA-positive patients had a significantly longer relapse-free survival time than ANCA-negative. The median prednisolone dose reduced at 6, 12 and 24 months from 12.5 to 7, 7.5 and 5 mg·day−1.
Thiel [64], 2017Retrospective cohort study14 patients; methotrexate, azathioprine, MMFVasculitic end-point:
BVAS of 0 and ≤7.5 mg·day−1 of prednisolone
28 patients with severe organ threatening EGPA previously refractory to other immunosuppressive treatment regimens were treated with rituximab (n=14) or cyclophosphamide (n=14). 36% on rituximab and 29% on cyclophosphamide achieved complete remission at 48 months. Both groups had a significant decrease in median prednisolone dose.
Mohammad [63], 2016Retrospective cohort study
41 patients; MMF, azathioprine, cyclophosphamide, methotrexate, i.v. immunoglobulinVasculitic end-point:
BVAS of 0 with <7.5 mg·day−1 of oral glucocorticoid
49% of patients achieved remission with 5% not requiring glucocorticoids at 12 months. 10% of patients relapsed after achieving remission. The average oral glucocorticoid requirement decreased. ANCA-positive patients had a higher remission rate at 12 months.
Omalizumab, anti-IgECelebi Sozener[67], 2018Retrospective cohort study
18 patients; other immunosuppressants allowed but not specified
Eosinophilic end-point:
Absence of asthma and/or ENT exacerbations with a prednisolone dosage of ≤7.5 mg day−1
Full response in 55.6% of patients, no response in 38.9%. Daily OCS dose and asthma exacerbations reduced over 52 weeks.
Jachiet [68], 2016Retrospective cohort study
17 patients; MMF, azathioprine, methotrexate
Eosinophilic and vasculitic end-points:
Response: absence of asthma and/or sino-nasal exacerbations with prednisolone dose <7.5 mg·day−1
BVAS and CRP levels
Full response in 35%, partial response in 30% of patients on ≥7.5 mg·day−1 of prednisolone. Reducing OCS was potentially associated with severe EGPA flares.
Reslizumab, anti-IL-5Manka [69], 2021Open-label pilot study10 patients; MMF, azathioprine, methotrexate
Eosinophilic and vasculitic end-points:
Worsening symptoms needing increased mOCS, physiological and blood markers
Reduction in OCS dose. At the end of the trial, 75% of patients were receiving OCS ≤5 mg and 37.5% of patients received 0 mg. 67.25% of patients were able to taper their OCS dose without having an exacerbation of their symptoms. Improvement of BVAS.
Kent [70], 2020Prospective cohort study9 patients; continuation of other immunosuppressants not mentionedEosinophilic and vasculitic end-points:
ACQ-7 score, mini-AQLQ, FEV1, BVAS, peripheral eosinophil count
Significant reduction in OCS dose from 23.4 mg·day−1 to 5.9 mg·day−1 at 48 months. All patients had a ≥50% reduction of median OCS dose. Significant improvement in mini-AQLQ score but not in ACQ-7 score, BVAS and spirometry.
Mepolizumab, anti-IL-5Bettiol [15], 2022Retrospective cohort study
191 patients; MMF, azathioprine, methotrexate, cyclosporine, rituximab, i.v. immunoglobulin
Vasculitic and eosinophilic end-point:
Response: No disease activity (BVAS=0) and prednisolone or prednisone dose (or equivalent) of ≤4 mg·day−1
Relapse includes worsening asthma symptoms
30.4% and 35.7% of patients achieved complete response at 12 and 24 months. 31% of patients relapsed after remission for a median of 6 months.
Steinfeld [71], 2019Randomised, placebo-controlled double-blind parallel-group trial68 patients; other immunosuppressants allowed but not specifiedVasculitic and eosinophilic end-points:
Remission: No disease activity (BVAS=0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg·day−1
Relapse: BVAS >0 or worsening ACQ-6
53% of patients achieved remission in the mepolizumab group versus 19% in the placebo group. 57% of patients in the mepolizumab group were able to reduce their OCS dose by ≥50% compared with 21% in the placebo group. 18% of patients were relapse-free in the placebo group compared with 44% in the mepolizumab group.
Wechsler [13], 2017Double-blind, parallel-group phase 3 trial68 patients; other immunosuppressants allowed but not specifiedVasculitic and eosinophilic end-points:
Remission: No disease activity (BVAS=0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg·day−1
Relapse includes worsening asthma symptoms
28% of patients receiving mepolizumab and 3% of placebo patients experienced ≥24 weeks of accrued remission. 32% of patients in the mepolizumab group versus 3% in the placebo group achieved remission at both 36 weeks and 48 weeks. Remission didn't occur in 47% of patients in the mepolizumab and 81% of patients in the placebo group. The relapse rate was 1.14 in the mepolizumab group and 2.27 in the placebo group.
Benralizumab, anti-IL-5RGuntur [46], 2021Prospective open-label pilot study10 patients; MMF, azathioprine, methotrexate
Eosinophilic and vasculitic end-points: Worsening symptoms needing increase in mOCS, ACQ, AQLQ, BVAS, physiological and blood markersMean OCS dose reduced at the end of the trial period from 15 mg·day−1 to 2 mg·day−1. Mean annualised exacerbation rate was lowest during treatment period compared with the pre- and post-treatment period. No difference in BVAS was noted at the beginning and end of the study.
Nanzer [14], 2020Retrospective study11 patients; continuation of other immunosuppressants not mentionedEosinophilic and vasculitic end-points:
ACQ-7 score, mini-AQLQ, FEV1, BVAS, peripheral eosinophil count
At 24 weeks, the median reduction in OCS dose was 50%. 73% of patients reduced their dose by over 50%. At 48 weeks, the median reduction in OCS dose was 65%. 89% of patients were able to reduce their dose by over 50%. A significant improvement was noted in BVAS at 24 and 48 weeks.

IL: interleukin; EGPA: eosinophilic granulomatosis with polyangiitis; BVAS: Birmingham Vasculitis Activity Score; ANCA: anti-neutrophil cytoplasmic antibody; MMF: mycophenolate mofetil; ENT: ear, nose and throat; OCS: oral corticosteroid; CRP: C-reactive protein; mOCS: maintenance OCS; ACQ: Asthma Control Questionnaire; AQLQ: Asthma Quality of Life Questionnaire; FEV1: forced expiratory volume in 1 s.