Long-Term Safety and Effectiveness of Mepolizumab 300 mg in Europe (Mepo LTF Study) (Mepo LTF)

Assessing The Long-Term Effectiveness and Safety of Mepolizumab 300mg/Month in the European Real-Life Setting (Mepo Long-term Study)

This observational study aims to evaluate the long-term effectiveness and safety of mepolizumab 300 mg/4 weeks in adults with eosinophilic granulomatosis with polyangiitis (EGPA) in the European real-life setting.

The main questions it aims to answer are:

• How effective is mepolizumab 300 mg/4 weeks over long-term follow-up in patients with EGPA?
• How safe is mepolizumab 300 mg/4 weeks during long-term treatment?
• What are the effects of switching mepolizumab dosage from 300 mg/4 weeks to 100 mg/4 weeks, or from 100 mg/4 weeks to 300 mg/4 weeks?

Participants already receiving mepolizumab as part of routine clinical practice. Researchers will retrospectively collect demographic, clinical, laboratory, and treatment-related data from medical records. For patients starting mepolizumab 300 mg/4 weeks, data will be collected from treatment initiation and during follow-up up to 60 months. For patients who change mepolizumab dose, data will also be collected at the time of dose switch and 3 months later.

Study Overview

• Status: Completed
• Conditions: Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss) (EGPA)
• Intervention / Treatment: Biological: Mepolizumab 300 mg

Detailed Description

BACKGROUND Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) characterized by asthma, ear- nose-throat (ENT) involvement, blood and tissue eosinophilia and systemic vasculitic manifestations (Emmi et al, Nat Rev Rheumatol 2023). The treatment mainly relies on systemic glucocorticoids and inhaled therapies for respiratory symptoms. Its course is usually chronic-relapsing, thus patients are at risk for permanent tissue or organ damage, also due to glucocorticoid-related toxicity. For this reason, immunosuppressive treatments are often required, to reduce disease activity, and also to spare glucocorticoids. (Emmi et al, Nat Rev Rheumatol 2023).

Among novel targeted therapies, Mepolizumab is a monoclonal antibody against interleukin (IL)-5, a cytokine involved in eosinophil maturation, differentiation and survival. Increased serum levels of IL-5 are observed in eosinophilic disorders, including EGPA, and a genome-wide association study identified the IL5 region as one of the main EGPA-associated loci. (Lyons et al, Nat Commun 2019).

Mepolizumab is approved at the dosage of 100mg/4 weeks subcutaneously for the treatment of severe eosinophilic asthma, and at the dosage of 300mg/4 weeks for hypereosinophilic syndrome (HES) and for EGPA, following the positive results of the MIRRA trial (Wechsler et al, NEJM 2017).

In the last years, a growing number of large observational cohort studies reported on the successful use of drugs targeting the IL-5 axis (including mepolizumab and the anti-IL5Ra benralizumab) for EGPA in the real-life clinical setting, also at the dosages approved for eosinophilic asthma (i.e., 100mg/4 weeks for mepolizumab; 300 mg/4 weeks for 3 administrations, then every 8 weeks for benralizumab) (Canzian et al, Arthritis Rheum 2020; Caminati et al, JACIP 2020; Bettiol et al, Arthritis Rheum 2022; Bettiol et al, Lancet Rheum 2023).

However, real-life effectiveness and safety data for these drugs are mostly limited to the first 12 months of treatment, with few longer-term data (not exceeding 24 months from treatment beginning) (Bettiol, et al, Arthritis Rheum 2022). Also, large observational cohorts mainly included patients on mepolizumab at the dosage approved for eosinophilic asthma (100mg/4 weeks), as it was the most frequently used (off-label) for EGPA across Europe, and real-life data on mepolizumab 300mg/4weeks are limited to smaller subgroups of patients.

Moreover, the effect of dose variation (escalation from 100 to 300mg/4 weeks or reduction from 300 to 100mg/4 weeks) in patients with inappropriate response or suboptimal tolerance to mepolizumab has never been assessed.

AIMS OF THE STUDY This study will fill an important gap, allowing to better understand the role and clinical positioning of anti-IL5 treatments for the long-term management of respiratory and systemic disease manifestations in EGPA patients initiating mepolizumab at the dosage of 300mg/4 weeks. Also, it will shed light on the effectiveness and safety of dosage switching (from 300 to 100mg/4 weeks or vice versa) in patients with inappropriate response or suboptimal tolerance to mepolizumab.

PRIMARY OBJECTIVE The primary objectives of the study will be the evaluation of the long-term effectiveness of mepolizumab in patients with newly diagnosed or relapsing and refractory EGPA treated with mepolizumab at the dosage of 300mg/4 weeks. Effectiveness will be assessed over a 60-month follow-up, considering the achievement of complete and partial response, variations in lung function, disease relapses and respiratory exacerbations.

SECONDARY OBJECTIVES

Key secondary objectives will include:

• The persistence on mepolizumab in patients with EGPA initiating the drug at the dosage of 300mg/4 weeks (timeframe: 60 months from mepolizumab beginning). Persistence will be evaluated in terms of dosage switches (from 300 to 100mg/4 weeks) and treatment discontinuation.
• The long-term safety of mepolizumab in patients with EGPA initiating the drug at the dosage of 300mg/4 weeks (timeframe: 60 months from mepolizumab beginning).
• The effectiveness of mepolizumab dosage-switching in patients with EGPA switching to a different mepolizumab dosage (from mepolizumab 300mg/4 weeks to 100mg/4 weeks or vice versa).

Effectiveness will be assessed in terms of achievement of complete or partial response and variations in lung function, separately for patients increasing or decreasing mepolizumab monthly dosage (timeframe: 3 months following dosage switch).

• The safety of mepolizumab dosage-switching in patients with EGPA switching to a different mepolizumab dosage (from Mepolizumab 300mg/4 weeks to 100mg/4 weeks or vice versa) (timeframe: 3 months following dosage switch).

PATIENTS AND METHODS STUDY DESIGN AND DATA COLLECTION A multicenter, retrospective study will be conducted. Demographic, clinical, biological and treatment-related data will be retrospectively collected from medical charts. For patients starting on mepolizumab 300mg/4 weeks, data will be collected at the time of mepolizumab starting (T0) and at 3, 6, 12, 24, 36, 48 and 60 months of follow-up (T3-T60). For patients changing mepolizumab dosage, data will be collected at time of dosage switch (TS0) and after 3 months (TS3).

STUDY POPULATION The study cohort will include a non-predefined number of adult EGPA patients who meet the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for EGPA (Grayson et al. 2022) or the criteria proposed in the MIRRA trial (Wechsler et al.2017) and receiving mepolizumab 300mg/4 weeks (either as first mepolizumab dosage or after a dosage increase from mepolizumab 100mg/4 weeks) in any calendar period at any of the 116 EGPA referral centres across European countries (Austria, France, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Russia, Serbia, Spain, Sweden, Switzerland, Turkey, United Kingdom, and Australia) participating to the European EGPA Study Group.

Written informed consent from all participants and approval from the local ethical committees will be obtained. The study will be conducted in accordance with the tenets of the Declaration of Helsinki.

Only patients who presented at least 3 months of available follow-up data after mepolizumab beginning (or after dosage switch), and with available data regarding BVAS and OCS at baseline and 3 months, will be included.

Finally, all patients with inadequate data or a follow-up shorter than 3 months after mepolizumab initiation or after dosage switch, and patients receiving mepolizumab within a clinical trial will be excluded.

DATA COLLECTION AND OUTCOME ANALYSIS:

1. Primary endpoints

   EFFECTIVENESS will be assessed in terms of:

   • ACHIEVEMENT OF COMPLETE AND PARTIAL RESPONSE: Complete response (CR) will be defined as no disease activity (Birmingham Vasculitis Activity Score, BVAS=0) and an oral corticosteroid dosage (OCS, prednisolone or prednisone dose or equivalent) ≤4.0 mg/day, as defined by the MIRRA trial and by previous studies (Bettiol A et al, Arthritis Rheum 2022; Bettiol A et al, Lancet Rheum 2023). Partial response (PR) will be defined as no disease activity and a prednisolone or prednisone dose >4.0 mg/day according to Bettiol A et al, Arthritis Rheum 2022; Bettiol A et al, Lancet Rheum 2023.

   At each follow-up timepoint, analysis will be conducted including only patients with data for both BVAS and OCS dosage. CR and PR rates will be calculated considering the number of patients meeting the CR or PR criteria (as defined above), over the total number of patients with available data for both BVAS and OCS dosage at the given timepoint.

   • VARIATIONS IN LUNG FUNCTION: Lung function will be assessed in terms of pre-bronchodilator forced expiratory volume in 1 second (FEV1).

   At baseline and at each follow-up timepoint, the median FEV1 will be calculated for patients with available data for the given timepoint. Also, for each patient percentage variation in the FEV1 at a given follow-up timepoint (TFU) will be calculated as (FEV1TFU- FEV1T0)/T0×100.

   • DISEASE RELAPSES: Disease relapses will be assessed only for patients who have achieved a CR at the previous follow-up timepoint, and will be defined by at least one the following criteria: a) active vasculitis (defined as BVAS>0) and/or b) worsening asthma and/or ENT manifestations leading to an increase in the OCS dose to more than 4.0 mg/day, an initiation of a new immunosuppressive therapy, or hospitalization, as defined by the MIRRA trial and by previous studies (Bettiol A et al, Arthritis Rheum 2022; Bettiol A et al, Lancet Rheum 2023).

   At each follow-up timepoint, disease relapse rates will be calculated considering the number of patients meeting the criteria for a disease relapse (as defined above), over the total number of patients with available data for the given timepoint and with CR at the previous follow-up timepoint.

   • RESPIRATORY EXACERBATIONS: Respiratory exacerbations will be defined as any of the following events: asthma attack needing an increase in OCS dosage >30%, emergency department admission related to asthma, and/or use of acute OCS, antibiotics, or short-acting beta-agonists (SABA).

   At each follow-up timepoint, respiratory exacerbations rates will be calculated considering the number of patients meeting the criteria for a respiratory exacerbation (as defined above), over the total number of patients with available data for the given timepoint.

2. Secondary endpoints

   • SAFETY: All adverse events (AEs) occurring during treatment and recorded in the medical charts will be retrieved and reported, irrespectively of the causality association with treatment. Serious adverse events (SAEs) will be assessed according to the World Health Organization criteria (European Medicines Agency. ICH Topic E 2 A - Clinical Safety Data Management: Definitions and Standards for Expedited Reporting. CPMP/ICH/377/95.).

   At each follow-up timepoint, AE and SAE rates will be calculated considering the number of patients with at least one AE or SAE, over the total number of patients with available data for the given timepoint.

   Individual ICSRs will not be generated from retrospective review of medical charts, and safety data will only be summarised as aggregated data in the study reports.

   • PERSISTENCE: Persistence will be assessed in terms of variations in Mepolizumab monthly dosage or treatment discontinuation.

   At each follow-up timepoint, dosage switch and discontinuation rates will be calculated considering the number of patients switching dosage or discontinuing treatment, over the total number of patients with available data for the given timepoint.

3. Additional Endpoints

Additional endpoints monitored at T0 and at all follow-up timepoints will include:

• CHANGES IN ORGAN MANIFESTATIONS (assessed separately from BVAS items): for each disease manifestation, the proportion of patients with active symptoms will be calculated over the total number of patients with available data for the given timepoint.
• OCS-SPARING EFFECT: at baseline and at each follow-up timepoint, the median daily OCS dosage will be calculated, for all patients with available data for the given timepoint. Also, the proportion of patients achieving a daily OCS dosage of 0 will be calculated over the total number of patients with available data for the given timepoint.
• DMARD-SPARING EFFECT: at each timepoint, the proportion of patients discontinuing a DMARD treatment (which was ongoing or was newly started at T0) will be calculated over the total number of patients with available data for the given timepoint.
• VARIATION IN THE PROPORTION OF ANCA-POSITIVE PATIENTS: at each timepoint, the proportion of ANCA positive patients will be calculated over the total number of patients with available results of ANCA testing for the given timepoint. ANCA-negativization rates will be assessed for patients with positive ANCA testing at T0, as the proportion of patients with a negative ANCA test at a given follow-up timepoint, over the total number of patients with available results of ANCA testing for the given timepoint and with positive ANCA at T0.
• VARIATION IN EOSINOPHIL COUNT: at baseline and at each follow-up timepoint, the median eosinophil count will be calculated for patients with available data for the given timepoint.

STATISTICAL PLAN AND DATA ANALYSIS Data will be presented as median value and interquartile range (IQR) for continuous variables, and as absolute number and percentage for qualitative variables. All analyses will include only patients with available data at the given timepoint; for each variable and timepoint, the total number of available observations will be reported.

For primary and secondary endpoints, rates will be reported as relative frequency (%), and 95% binomial exact confidence intervals (CIs) will be estimated.

Three continuous variables (OCS dose, FEV1 and eosinophil count), chosen based on their clinical relevance, will be formally compared across the different follow-up timepoints (T0-T60), using the MMRM models comparing follow-up timepoints (months 3, 6, … 60) with the baseline (month 0).

Only patients with available data at all timepoints will be included in these analyses. The corresponding parametric tests will be used in the case the distribution of the data will follow a normal distribution.

Statistical analyses will be performed using Stata (version 14) and Graphpad Prism (version 9).

SAMPLE SIZE JUSTIFICATION No formal sample size calculation is performed. Indeed, the study cohort will include a non-predefined number of EGPA patients receiving Mepolizumab 300mg/4 weeks in any calendar period at any of the 116 EGPA referral centres participating to the European EGPA Study Group, according to the inclusion and exclusion criteria defined above.

Based on a feasibility assessment performed during the 8th EESG Meeting (26th Sept 2024, Florence, Italy) with partners from these centres, it is expected that 300-350 patients will be included in the study. Moreover, based on the feasibility assessment coming from the same meeting, we expect to collect data from approximately:

300-350 patients at 3 months 280-300 at 6 months 200-230 at 12 months 150-170 at 24 months 80-100 at 36 months, at T36 months and T48 months 50 at 60 months These estimates reflect expected lost in follow-up over time, which is common in retrospective real-world observational studies.

Based on previous data [Bettiol A, Arthritis Rheum 2022], we anticipate that CR at 24 months will be 58% in patients on Mepolizumab 300mg/months (expected n=170), and 33% in patients on Mepolizumab 100mg/month (expected n=130). Considering a type I error of 5%, the expected power of the study is 99%.

• Study Type: Observational
• Enrollment (Actual): 591

Contacts and Locations

Study Locations

• Italy
  • Florence
    • Florence, Florence, Italy, 50134
      • University of Florence

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with eosinophilic granulomatosis with polyangiitis (EGPA) receiving mepolizumab 300 mg/4 weeks in routine clinical practice at participating European EGPA referral centers, either as the initial mepolizumab regimen or after dose escalation from 100 mg/4 weeks.

Description

Inclusion Criteria:

• Adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). Patients who meet the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) Classification Criteria for EGPA or the criteria proposed in the MIRRA trial.
• Patients receiving mepolizumab 300 mg/4 weeks, either as the first mepolizumab regimen or after dose escalation from mepolizumab 100 mg/4 weeks.
• Availability of at least 3 months of follow-up data after mepolizumab initiation or after dose switch.
• Written informed consent.

Exclusion Criteria:

- Follow-up shorter than 3 months after mepolizumab initiation or after dose switch.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

EGPA Patients on Mepolizumab 300 mg/4 Weeks; Adult patients with EGPA treated with mepolizumab 300 mg/4 weeks in routine clinical practice. Retrospective data are collected from medical records through follow-up up to 60 months, including assessment after dose switching when applicable.

Biological: Mepolizumab 300 mg; Mepolizumab administered subcutaneously at a dose of 300 mg every 4 weeks in routine clinical practice for adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). In this retrospective observational study, patients may receive mepolizumab 300 mg/4 weeks as the initial regimen or after dose escalation from 100 mg/4 weeks. Dose changes from 300 mg/4 weeks to 100 mg/4 weeks, or from 100 mg/4 weeks to 300 mg/4 weeks, are also evaluated when they occur during routine care; no study-specific treatment is assigned.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete and Partial Response	Proportion of patients achieving complete response or partial response during follow-up. Complete response is defined as no disease activity (BVAS=0) and oral corticosteroid dose ≤4.0 mg/day. Partial response is defined as no disease activity (BVAS=0) and oral corticosteroid dose >4.0 mg/day.	Baseline and up to 60 months (at 3, 6, 12, 24, 36, 48, and 60 months)
Change in Lung Function	Change in pre-bronchodilator forced expiratory volume in 1 second (FEV1) during follow-up.	Baseline and up to 60 months (at 3, 6, 12, 24, 36, 48, and 60 months)
Disease relapses	Proportion of patients with disease relapse during follow-up. Relapse is defined as active vasculitis (BVAS>0) and/or worsening asthma or ENT manifestations leading to oral corticosteroid increase to >4.0 mg/day, initiation of a new immunosuppressive therapy, or hospitalization.	Up to 60 months (assessed at 3, 6, 12, 24, 36, 48, and 60 months)
Respiratory Exacerbations	Proportion of patients with respiratory exacerbations during follow-up. Respiratory exacerbations are defined as asthma attack requiring an increase in oral corticosteroid dose >30%, emergency department admission related to asthma, and/or use of acute oral corticosteroids, antibiotics, or short-acting beta-agonists.	Up to 60 months (assessed at 3, 6, 12, 24, 36, 48, and 60 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Proportion of patients with at least one adverse event (AE) or serious adverse event (SAE) during treatment with mepolizumab 300 mg/4 weeks. Safety events are retrieved from medical charts and summarized as aggregated data.	Up to 60 months from mepolizumab initiation (at 3, 6, 12, 24, 36, 48, and 60 months)
Persistance	Persistence on mepolizumab, assessed in terms of dose switching and treatment discontinuation during follow-up.	Up to 60 months from mepolizumab initiation (at 3, 6, 12, 24, 36, 48, and 60 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Organ Manifestations	The proportion of patients with active symptoms will be calculated over the total number of patients with available data for the given timepoint.	Baseline and up to 60 months (at 3, 6, 12, 24, 36, 48, and 60 months)
Oral Corticosteroid-Sparing Effect	Median daily oral corticosteroid dose and proportion of patients achieving a daily oral corticosteroid dose of 0 during follow-up	Baseline and up to 60 months (at 3, 6, 12, 24, 36, 48, and 60 months)
DMARD-Sparing Effect	Proportion of patients discontinuing DMARD treatment that was ongoing or newly started at baseline.	Baseline and up to 60 months (at 3, 6, 12, 24, 36, 48, and 60 months)
Variation in ANCA Positivity	Proportion of ANCA-positive patients at each timepoint and ANCA negativization among patients positive for ANCA at baseline.	Baseline and up to 60 months (at 3, 6, 12, 24, 36, 48, and 60 months)
Variation in Eosinophil Count	Median eosinophil count during follow-up in patients with available data for each timepoint.	Baseline and up to 60 months (at 3, 6, 12, 24, 36, 48, and 60 months)

Collaborators and Investigators

• Sponsor: European EGPA Study Group
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• Wechsler ME, Akuthota P, Jayne D, Khoury P, Klion A, Langford CA, Merkel PA, Moosig F, Specks U, Cid MC, Luqmani R, Brown J, Mallett S, Philipson R, Yancey SW, Steinfeld J, Weller PF, Gleich GJ; EGPA Mepolizumab Study Team. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2017 May 18;376(20):1921-1932. doi: 10.1056/NEJMoa1702079.
• Vultaggio A, Nencini F, Bormioli S, Vivarelli E, Dies L, Rossi O, Parronchi P, Maggi E, Matucci A. Low-Dose Mepolizumab Effectiveness in Patients Suffering From Eosinophilic Granulomatosis With Polyangiitis. Allergy Asthma Immunol Res. 2020 Sep;12(5):885-893. doi: 10.4168/aair.2020.12.5.885.
• Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990 Aug;33(8):1094-100. doi: 10.1002/art.1780330806.
• Lyons PA, Peters JE, Alberici F, Liley J, Coulson RMR, Astle W, Baldini C, Bonatti F, Cid MC, Elding H, Emmi G, Epplen J, Guillevin L, Jayne DRW, Jiang T, Gunnarsson I, Lamprecht P, Leslie S, Little MA, Martorana D, Moosig F, Neumann T, Ohlsson S, Quickert S, Ramirez GA, Rewerska B, Schett G, Sinico RA, Szczeklik W, Tesar V, Vukcevic D; European Vasculitis Genetics Consortium; Terrier B, Watts RA, Vaglio A, Holle JU, Wallace C, Smith KGC. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status. Nat Commun. 2019 Nov 12;10(1):5120. doi: 10.1038/s41467-019-12515-9.
• Grayson PC, Ponte C, Suppiah R, Robson JC, Craven A, Judge A, Khalid S, Hutchings A, Luqmani RA, Watts RA, Merkel PA; DCVAS Study Group. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis With Polyangiitis. Arthritis Rheumatol. 2022 Mar;74(3):386-392. doi: 10.1002/art.41982. Epub 2022 Feb 2.
• Emmi G, Bettiol A, Gelain E, Bajema IM, Berti A, Burns S, Cid MC, Cohen Tervaert JW, Cottin V, Durante E, Holle JU, Mahr AD, Del Pero MM, Marvisi C, Mills J, Moiseev S, Moosig F, Mukhtyar C, Neumann T, Olivotto I, Salvarani C, Seeliger B, Sinico RA, Taille C, Terrier B, Venhoff N, Bertsias G, Guillevin L, Jayne DRW, Vaglio A. Evidence-Based Guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis. Nat Rev Rheumatol. 2023 Jun;19(6):378-393. doi: 10.1038/s41584-023-00958-w. Epub 2023 May 9.
• Canzian A, Venhoff N, Urban ML, Sartorelli S, Ruppert AM, Groh M, Girszyn N, Taille C, Maurier F, Cottin V, de Moreuil C, Germain V, Samson M, Jachiet M, Denis L, Rieu V, Smets P, Pugnet G, Deroux A, Durel CA, Aouba A, Cathebras P, Deligny C, Faguer S, Gil H, Godeau B, Lifermann F, Phin-Huynh S, Ruivard M, Bonniaud P, Puechal X, Kahn JE, Thiel J, Dagna L, Guillevin L, Vaglio A, Emmi G, Terrier B; 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 Mar;73(3):498-503. doi: 10.1002/art.41534. Epub 2021 Jan 23.
• Caminati M, Crisafulli E, Lunardi C, Micheletto C, Festi G, Maule M, Giollo A, Orsolini G, Senna G. Mepolizumab 100 mg in severe asthmatic patients with EGPA in remission phase. J Allergy Clin Immunol Pract. 2021 Mar;9(3):1386-1388. doi: 10.1016/j.jaip.2020.09.025. Epub 2020 Oct 1. No abstract available.
• Bettiol A, Urban ML, Padoan R, Groh M, Lopalco G, Egan A, Cottin V, Fraticelli P, Crimi C, Del Giacco S, Losappio L, Moi L, Cinetto F, Caminati M, Novikov P, Berti A, Cameli P, Cathebras P, Coppola A, Durel CA, Folci M, Lo Gullo A, Lombardi C, Monti S, Parronchi P, Rivera CM, Solans R, Vacca A, Espigol-Frigole G, Guarnieri G, Bianchi FC, Marchi MR, Tcherakian C, Kahn JE, Iannone F, Venerito V, Desaintjean C, Moroncini G, Nolasco S, Costanzo GAML, Schroeder JW, Ribi C, Tesi M, Gelain E, Mattioli I, Bello F, Jayne D, Prisco D, Vaglio A, Emmi G; European EGPA Study Group. Benralizumab for eosinophilic granulomatosis with polyangiitis: a retrospective, multicentre, cohort study. Lancet Rheumatol. 2023 Dec;5(12):e707-e715. doi: 10.1016/S2665-9913(23)00243-6. Epub 2023 Nov 6.
• Bettiol A, Urban ML, Dagna L, Cottin V, Franceschini F, Del Giacco S, Schiavon F, Neumann T, Lopalco G, Novikov P, Baldini C, Lombardi C, Berti A, Alberici F, Folci M, Negrini S, Sinico RA, Quartuccio L, Lunardi C, Parronchi P, Moosig F, Espigol-Frigole G, Schroeder J, Kernder AL, Monti S, Silvagni E, Crimi C, Cinetto F, Fraticelli P, Roccatello D, Vacca A, Mohammad AJ, Hellmich B, Samson M, Bargagli E, Cohen Tervaert JW, Ribi C, Fiori D, Bello F, Fagni F, Moroni L, Ramirez GA, Nasser M, Marvisi C, Toniati P, Firinu D, Padoan R, Egan A, Seeliger B, Iannone F, Salvarani C, Jayne D, Prisco D, Vaglio A, Emmi G; European EGPA Study Group. Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study. Arthritis Rheumatol. 2022 Feb;74(2):295-306. doi: 10.1002/art.41943. Epub 2021 Dec 30.
• Bettiol A, Urban ML, Bello F, Fiori D, Mattioli I, Lopalco G, Iannone F, Egan A, Dagna L, Caminati M, Negrini S, Bargagli E, Folci M, Franceschini F, Padoan R, Flossmann O, Solans R, Schroeder J, Andre M, Moi L, Parronchi P, Roccatello D, Sciascia S, Jayne D, Prisco D, Vaglio A, Emmi G; European EGPA Study Group. Sequential rituximab and mepolizumab in eosinophilic granulomatosis with polyangiitis (EGPA): a European multicentre observational study. Ann Rheum Dis. 2022 Dec;81(12):1769-1772. doi: 10.1136/ard-2022-222776. Epub 2022 Jul 18. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2025
• Primary Completion (Actual): March 31, 2026
• Study Completion (Actual): March 31, 2026

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Mepolizumab; Vasculitis; Eosinophilic Granulomatosis with Polyangiitis; EGPA; Real-world study
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Skin Diseases, Vascular; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granuloma; Systemic Vasculitis; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Churg-Strauss Syndrome; Vasculitis; mepolizumab
• Other Study ID Numbers: 22336 _ oss

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared due to privacy, confidentiality, and applicable ethics and data protection requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No