Treatment With Mepolizumab on Patients With Severe Refractory Eosinophilic Asthma

Biomarkers Evaluation and Effect of Mepolizumab on Lower and Upper Airways Inflammation in Severe Refractory Eosinophilic Asthma

Understanding how Interleukin-5 blockade modulates both immune and metabolic pathways may clarify the multidimensional impact of biologic therapy in severe eosinophilic asthma. Therefore, this study aimed to assess the impact of mepolizumab on the nasal, bronchial, and systemic metabolomic profiles of consecutive patients with SEA and to explore the associations between these compartment-specific changes and clinical, inflammatory, and functional outcomes.

Study Overview

• Status: Completed
• Conditions: Severe Eosinophilic Asthma
• Intervention / Treatment: Drug: Mepolizumab

Detailed Description

We conducted a prospective, observational, multicenter cohort study of SEA adult individuals initiating mepolizumab, with 12-month follow-up. Consecutive patients referred to the Pulmonary Rehabilitation Units of the Istituti Clinici Scientifici Maugeri IRCCS in Telese Terme and Tradate, Italy, from September 2021 to September 2023, were screened for eligibility based on the following inclusion criteria: eligibility for mepolizumab treatment according to clinical practice; age between 18 and 75 years; diagnosis of severe eosinophilic refractory asthma, defined as peripheral blood eosinophil count (BEC) > 300 cells/μL and at least two documented exacerbations within the previous 12 months; and ongoing treatment with high daily doses of inhaled corticosteroids (ICS) combined with long-acting β2-agonists (LABA), plus at least one additional controller medication for a minimum of 12 months.

Exclusion criteria included: current smoking; diagnosis of other chronic pulmonary diseases; coexisting chronic rhinosinusitis with nasal polyps; use of systemic corticosteroids at any dose within the 6 weeks prior to enrollment; use of immunosuppressive therapies; receipt of live attenuated vaccines within 30 days prior to enrollment; current or recent history (within the last 5 years) of malignancy, except in cases of complete remission; diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA); upper or lower respiratory tract infections within 30 days prior to signing informed consent or during the screening/run-in period; any clinically significant abnormalities identified during screening through physical examination, vital signs assessment, hematology, or clinical chemistry, which, in the opinion of the investigator, could pose a risk to patient safety or interfere with study outcomes or compliance. Additional exclusion criteria were: known immunodeficiency (primary or secondary); pregnancy; concurrent treatment with other biologics for asthma or other conditions (except for stable allergen immunotherapy, defined as an unchanged dose and regimen at screening); prior biologic therapy for asthma within 6 months before starting mepolizumab; planned surgical procedures during the study period; and participation in another interventional or post-authorization safety study.

The study lasted 24 months, including a 12-month enrollment period followed by a 12-month follow-up. Timepoints at 6 and 12 months were prespecified to capture early consolidation of treatment response and its one-year persistence, in alignment with routine follow up. Prior to inclusion, all participants underwent a clinical examination to assess eligibility. Clinical history was recorded, including age at asthma onset, smoking status, aspirin intolerance, number of exacerbations in the previous year, and asthma control level. Smoking status was recorded as never, former, or current, and current smokers were excluded. Occupational and specific environmental exposures were not systematically collected in this study. Evaluations were performed at baseline (T0), 6 (T6), and 12 months (T12) after initiation of treatment. At each timepoint, respiratory function was assessed and multiple biological matrices were collected to test markers of T2 inflammation and enable metabolomic profiling.

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• Italy
  • BN
    • Telese Terme, BN, Italy, 82037
      • Istituti Clinici Scientifici Maugeri IRCCS
  • Varese
    • Tradate, Varese, Italy
      • Istituti Clinici Scientifici Maugeri IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

We will enroll patients with severe refractory eosinophilic asthma for whom treatment with mepolizumab is indicated, according to the AIFA recommendations.

Description

Inclusion Criteria:

• Eligibility for mepolizumab treatment according to clinical practice;
• age between 18 and 75 years;
• diagnosis of severe eosinophilic refractory asthma, defined as peripheral blood eosinophil count (BEC) > 300 cells/μL and at least two documented exacerbations within the previous 12 months;
• ongoing treatment with high daily doses of inhaled corticosteroids (ICS) combined with long-acting β2-agonists (LABA), plus at least one additional controller medication for a minimum of 12 months.

Exclusion criteria:

• current smoking;
• diagnosis of other chronic pulmonary diseases;
• coexisting chronic rhinosinusitis with nasal polyps;
• use of systemic corticosteroids at any dose within the 6 weeks prior to enrollment;
• use of immunosuppressive therapies;
• receipt of live attenuated vaccines within 30 days prior to enrollment;
• current or recent history (within the last 5 years) of malignancy, except in cases of complete remission;
• diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA);
• upper or lower respiratory tract infections within 30 days prior to signing informed consent or during the screening/run-in period;
• any clinically significant abnormalities identified during screening through physical examination, vital signs assessment, hematology, or clinical chemistry, which, in the opinion of the investigator, could pose a risk to patient safety or interfere with study outcomes or compliance.
• known immunodeficiency (primary or secondary);
• pregnancy;
• concurrent treatment with other biologics for asthma or other conditions (except for stable allergen immunotherapy, defined as an unchanged dose and regimen at screening); prior biologic therapy for asthma within 6 months before starting mepolizumab; planned surgical procedures during the study period;
• participation in another interventional or post-authorization safety study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Ecologic or Community
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Severe eosinophilic asthma; Patients with severe refractory eosinophilic asthma	Drug: Mepolizumab; The effects of treatment with Mepolizumab were evaluated on clinical and laboratory markers of systemic inflammation during a 12 months follow-up period in multiple biological matrices.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of exacerbations	episodes of acute worsening of symptoms	Baseline T0; 6 months (T6); 12 months (T12)
Asthma Control Test (ACT)	patient self-reported questionnaire, score	Baseline T0; 6 months (T6); 12 months (T12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory markers (Interleukins, TGF-beta, GM-CSF)	by ELISA test of serum, nasal secretions and exhaled breath condensate, measured as pg/mLof serum	Baseline T0; 6 months (T6); 12 months (T12)
1H-NMR-based metabolomic profiling	achieved by 1H-NMR spectroscopy of serum, nasal secretions and exhaled breath condensate	Baseline T0; 6 months (T6); 12 months (T12)
peripheral blood eosinophil count (BEC)	measured by count of cells/uL of blood	Baseline T0; 6 months (T6); 12 months (T12)
Forced expiratory volume (FEV1)	measured by spirometry, as L	Baseline T0; 6 months (T6); 12 months (T12)
Fractional Exhaled nitric oxide (FeNO)	measured by an automated electrochemical analyzer (HypAir FeNO), as ppb	Baseline T0; 6 months (T6); 12 months (T12)

Collaborators and Investigators

• Sponsor: Istituti Clinici Scientifici Maugeri SpA
• Collaborators: University of Palermo; National Research Council

Publications and helpful links

General Publications

• Maniscalco M, Ambrosino P, Candia C, Di Stefano A, Gnemmi I, Zappa M, Ambrosino N, Visca D, Motta A. Cytokine and Metabolomic Signatures of Mepolizumab Response Across Upper and Lower Airway Compartments in Severe Eosinophilic Asthma: An Exploratory Analysis. Pharmaceuticals (Basel). 2025 Nov 10;18(11):1704. doi: 10.3390/ph18111704.

Helpful Links

• Pubblication

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2021
• Primary Completion (Actual): September 29, 2023
• Study Completion (Actual): September 2, 2025

Study Registration Dates

• First Submitted: July 15, 2021
• First Submitted That Met QC Criteria: September 21, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: rehabilitation; asthma; mepolizumab; inflammation; chronic respiratory disease
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Asthma; Pulmonary Eosinophilia; Inflammation; mepolizumab
• Other Study ID Numbers: Pascale 09/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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