Effectiveness of Anti-IL-5/IL5R Inhibitors

Assessment and Prediction of the Effectiveness of Mepolizumab Anti-IL-5/IL5R Inhibitors in a Real-world Setting

The goal of this observational study is to assess the response to treatment, in patients 18 years and older diagnosed with severe asthma in whom an IL5/IL5R antagonists was initiated between 2012 and 2020.

The main question[s] it aims to answer are:

• What is the response rate after one year of treatment with IL5/IL5R antagonists.
• What is the response and remission rate after one year of treatment with IL5/IL5R antagonists in subjects who fullfilled the original randomized control trials (RCTs) inclusion criteria compared with those who did not.

Study Overview

• Status: Completed
• Conditions: Severe Asthma
• Intervention / Treatment: Drug: IL5/IL5R Antagonists

Detailed Description

IL5/IL5-receptor (IL5R) antagonists are effective in reducing asthma exacerbations and have a corticosteroid sparing effect in selected severe eosinophilic asthmatics. The original randomized clinical trials that assessed the efficacy of IL5/IL5-R antagonists included highly selected patients who are not necessarily representative of the asthmatic population treated with IL5/IL5R antagonists in clinical practice.

The aims of this study are:

1. To assess the response to treatment, in patients 18 years and older diagnosed with severe asthma in whom an IL5/IL5R antagonists was initiated between 2012 and 2020.
2. To compare the response and remission rate after one year of treatment with IL5/IL5-R antagonists in asthmatics who would and would have not met the inclusion criteria of the original randomized clinical trials.

We will perform a retrospective cohort study using data from the hospital charts of severe asthmatics treated with mepolizumab, reslizumab or benralizumab between November 2012 and December 2020 at the outpatient asthma clinic of a tertiary center (Sacre-Coeur Hospital) in Montreal. Cohort entry (CE) will be defined as the first prescription filled of IL5/IL5R antagonists. Authorization from the research ethics committee of the CIUSSS du Nord-de-l'île-de-Montréal and from the director of Professional Services was obtained.

Statistical analysis Descriptive statistics will be used to summarize clinical, functional, and demographic characteristics of the patients of the whole cohort, as well as of the RCT in group and RCT out group. Baseline data will be recorded on the date closest to cohort entry. Results will be expressed as mean and standard deviation, except for data with a non-normal distribution, which were expressed as median and interquartile ranges and proportions for categorical variables. Chi-squared test and Student's t test will be used to compare patients' characteristics between RCT in group and RCT out group. All tests will be two-tailed, and the statistical significance level will be set at 0.05.

Logistic regression analyses will be performed to identify factors associated with a positive response to treatment as well as the achievement of remission on treatment.

• Study Type: Observational
• Enrollment (Actual): 108

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, HJ1C5
      • Hopital du Sacre-Coeur de Montreal

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients 18 years and older diagnosed with severe asthma in whom an IL5/IL5R antagonist was initiated between 2012 and 2020 for were included. Data recorded in the year preceding the initiation of IL5/IL5R antagonist were compared with data recorded in the year following the initiation of the biological therapy.

Subjects who were aged 75 years or younger, had a smoking history of less than 10 pack-year, a FEV1 of less than 80% of the predicted value along with FEV1 reversibility of at least 12% and 200 ml in the previous year were considered as fulfilling the inclusion criteria of the original RCTs (RCT in group). Subjects who did not meet one of those criteria were considered as not fulfilling the original RCT inclusion criteria (RCT out group).

Description

Inclusion Criteria:

All patients 18 years and older diagnosed with severe asthma in whom an IL5/IL5R antagonist was initiated at the outpatient asthma clinic of a tertiary center (Sacre-Coeur Hospital) in Montreal.c between 2012 and 2020.

Exclusion Criteria:

None

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to IL5/IL5R Antagonist	Percentage of subjects achieving response to IL5/IL5R antagonists. A response to treatment was defined as a reduction of asthma exacerbations of at least 50% or a 50% or higher reduction of the OCS doses for steroid dependant patients in the year following the initiation of an IL5/IL5R antagonist compared to the year preceding the initiation of the treatment.	one year
Remission Rate With IL5/IL5R Antagonist	Percentage of subjects achieving asthma remission. Clinical remission on treatment at one year was defined as no asthma exacerbation, no treatment with oral corticosteroid and a less than 10% decrease in pre-bronchodilator FEV1 compared with baseline value.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to IL5/IL5R antagonists one year after CE among subjects who did and did not fullfill the inclusion criteria of the original randomized control trials.	A response to treatment was defined as a reduction of asthma exacerbations of at least 50% or a 50% or higher reduction of the OCS doses for steroid dependant patients in the year following the initiation of an IL5/IL5R antagonist compared to the year preceding the initiation of the treatment.	one year
Clinical remission of asthma after treatment with IL5/IL5R antagonists among subjects who did and did not fullfill the inclusion criteria of the original randomized control trials.	Clinical remission on treatment at one year was defined as no asthma exacerbation, no treatment with oral corticosteroid and a less than 10% decrease in pre-bronchodilator FEV1 compared with baseline value.	one year

Collaborators and Investigators

• Sponsor: Hopital du Sacre-Coeur de Montreal
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Catherine Lemiere, MD, Hopital du Sacre-Coeur de Montreal

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2021
• Primary Completion (Actual): June 13, 2023
• Study Completion (Actual): November 29, 2023

Study Registration Dates

• First Submitted: January 25, 2024
• First Submitted That Met QC Criteria: January 25, 2024
• First Posted (Actual): February 2, 2024

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Severe Asthma; IL5 antagonist
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma; Respiratory System Agents; Anti-Asthmatic Agents; Benralizumab
• Other Study ID Numbers: 2021-2190

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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