The Effect of Anti-IL17 on Airway Hyperresponsiveness and Resistance

March 14, 2025 updated by: Jonas Baekdal, Copenhagen University Hospital, Hvidovre

The Effect of Anti-IL17 on Airway Hyperresponsiveness and Resistance: a Longitudinal Cohort Study

This observational longitudinal cohort study aims to assess the effect of monoclonal antibodies targeting interleukin 17 (anti-IL-17) on airway hyperreactivity and airway resistance. The study involves adult participants suffering from dermatological or rheumatological illness, who are planning to start treatment with monoclonal antibodies targeting interleukin 17 as a part of the treatment of these diseases.

The primary outcome of this study will be changes in airway hyperresponsiveness to methacholine challenge reported as response-dose-ratio before and after initiation of anti-IL17 treatment regardless of presence of respiratory disease. Furthermore, the potential effect of anti-IL-17 on airway resistance will be assessed using conventional spirometry for measuring changes in FEV1 and Airwave oscillometry.

A reduced degree of airway hyperreactivity and airway resistance after initiating ani-IL-17 could indicate effectiveness of anti-IL-17 in asthma patients which would have to be examined further in a population of asthma patients.

Study Overview

Status

Recruiting

Conditions

Asthma

Detailed Description

Background:

Antibodies towards interleukin 17 (IL-17) are approved for treating various rheumatological and dermatological diseases like psoriatic arthritis, ankylosing spondylitis and plaque psoriasis. In recent years, IL-17 has been suggested as a potential driver of severe non-Type 2 asthma because of its' association with glucocorticoid resistance and symptoms of severe asthma. Since conventional treatment is often less effective in patients suffering from non-Type 2 asthma, sometimes adequate disease control cannot be achieved, thus limiting these patients' opportunity for physical exercise, and thereby increasing the risk of obesity and heart disease. Furthermore, obesity has been shown to increase asthma symptoms and frequency of exacerbations.

IL-17 has shown to be upregulated by female sex hormones which may explain the sex specific traits of severe non-Type 2 asthma. In obese mice, IL-17 has shown to be directly responsible for the induction of airway hyperresponsiveness (AHR), thus making it a potential target for treatment. It is especially of interest that none of the previously performed human studies have investigated the effect of blocking IL-17 on AHR. A previous study investigating the effect of blocking IL-17 on lung function, measured as change in FEV1 (forced expiratory volume in 1 second) in moderate to severe patients with asthma, did not find any significant effect. However, this study included both men and women as well as lean and obese participants which could explain the lack of clinical difference. Another previous study also showed no effect of anti-IL17 in general. However, this study showed that those with the greatest reversibility to bronchodilators had the best improvement in symptoms. Although negative, these studies brought us further by showing that anti-IL-17 treatment was safe and tolerable for patients with moderate to severe asthma. Oscillometry has been known for several decades but is only on its' way into clinical practice. Oscillometry is more sensitive than spirometry in detecting small airway disease and AHR. Thus, using oscillometry in studies investigating airway resistance in asthmatic individuals in addition to spirometry, is warranted.

Objectives The overall objective of this study is to determine whether AHR and airway resistance is reduced when initiating treatment with anti-IL17 antibodies for other indications than pulmonary disease. Changes in AHR to methacholine challenge will be reported as response-dose-ratio before and after initiation of anti-IL17. Airway resistance will be assessed using both conventional spirometry for measuring changes in FEV1 and Airwave oscillometry.

Hypothesis

Primary hypothesis: In rheumatologic and dermatological patients commencing anti-IL-17 for other reasons than pulmonary disease, we expect a reduction in airway responsiveness to methacholine challenge after 2-4 months of treatment when compared to prior to initiation of anti-IL-17 treatment.

Secondary hypotheses: Anti-IL17 treatment will show no effect on FEV1, measured using conventional spirometry but will improve measures of airwave oscillometry.

Study Type

Observational

Enrollment (Estimated)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Jonas A Baekdal, MD
Phone Number: +45 60134687
Email: jonas.aggerholm.baekdal.02@regionh.dk

Study Locations

Denmark
- Capital Region
  - Hvidovre, Capital Region, Denmark, 2650
    - Recruiting
    - Respiratory Research Unit Hvidovre Department of Respiratory Medicine, Copenhagen University Hospital
    - Contact:
      
      jonas A Baekdal, MD
      
      Phone Number: +4523497817
      
      Email: jonas.aggerholm.baekdal.02@regionh.dk

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Participants will be adult (18 years or older) rheumatologic og dermatologic patients planning to start treatment with anti-IL-17 antibodies. Participants must not have any conditions excluding them from performing a methacholine challenge (Previous anaphylactic shock, current pregnancy, recent cardiac disease, or FEV1 below 1,5L or 60% of expected. Furthermore, patients must not have been treated with systemic corticosteroids within the past 6 weeks.

Description

Inclusion Criteria:

Patients planning to start treatment with anti-IL-17 antibodies

Exclusion Criteria:

Current pregnancy
FEV1 < 1.5L or less than 60% of predicted value expected.
Previous anaphylactic shock or severe allergic reaction to medicine
Uncontrolled hypertension
Myocardial infarction or stroke within the last 3 months
Known aortic aneurysm
Recent eye surgery or risk of elevated intracranial pressure
Treatment with systemic corticosteroids within 6 weeks

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airway hyperresponsiveness Time Frame: approximately 4 months	Airway responsiveness to methacholine challenge before and after initiation of anti-IL-17 treatment reported as a dose-response-ratio	approximately 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airway resistance Time Frame: approximately 4 months	Airway resistance will be assessed using both conventional spirometry for measuring changes in FEV1 and Airwave oscillometry	approximately 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Copenhagen University Hospital, Hvidovre

Investigators

Principal Investigator: Jonas A Baekdal, MD, University hospital, Hvidovre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 2, 2024

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

January 16, 2024

First Submitted That Met QC Criteria

January 16, 2024

First Posted (Actual)

January 25, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 14, 2025

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

AHR after Anti-IL-17

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

Studies a U.S. FDA-regulated device product

product manufactured in and exported from the U.S.

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The Effect of Anti-IL17 on Airway Hyperresponsiveness and Resistance