PROCLAIM: Poor Response to Monoclonal Therapy in Asthma
Study Details
Study Description
Brief Summary
Asthma affects 8% of the entire population. 4-5% of asthma sufferers have severe asthma, characterised by recurrent exacerbations (worsening of symptoms leading to the person having a bout of corticosteroids and/or antibiotics), significant symptoms and lack of response to the most widely used therapy, corticosteroids.
There is now new types of treatments (antibody drugs) which are licensed to manage severe asthma such as Anti-IL5. There is evidence Anti-IL5 and other similar antibody drugs are effective at reducing asthma exacerbations and reduce the need for oral corticosteroids for those that have severe asthma.
However, some patients respond poorly to Anti-IL5 and the investigators would like to find out why this happens. It is hoped that the investigators can identify the mechanism of poor treatment response to Anti-IL5. It is also hoped that the investigators can understand why symptoms worsen to the point of requiring antibiotics and/or steroids (also known as an exacerbation) for those prescribed Anti-IL5.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Severe asthma Untreated by anti-IL5 treatment for severe asthma at point of recruitment. To be prescribed anti-IL5 as part of their treatment following consent. Note: Anti-IL5 treatment is prescribed as per agreed multidisciplinary team meeting, outside of the decision to enrol the patient on the study, and is administered by the clinical team as part of the patient's clinical care outside of the research study. |
Drug: Anti-IL5 Antibody
Asthma group: Anti-IL5 treatment Control group: No biologic.
Procedure: Bronchoscopy
Optional for both arms
|
| Healthy control Control group without respiratory condition |
Procedure: Bronchoscopy
Optional for both arms
|
Outcome Measures
Primary Outcome Measures
- Identification of mechanisms associated with poor response to anti-IL5 therapy [12 months]
Identification of mechanisms associated with poor response to anti-IL5 therapy. A poor response is defined as an inability to halve the pre-treatment annualised exacerbation rate; an asthma exacerbation is defined as a worsening of asthma symptoms necessitating a short burst of oral corticosteroids, or a doubling of maintenance oral corticosteroid treatment dose.
- An improvement in FEV1 as assessed by spirometry [12 months]
Treatment response as assessed as a clinically meaningful improvement in asthma control (ACQ change of >0.5).
- A clinically meaningful improvement in asthma control as assessed by ACQ [12 months]
An improvement in FEV1 of >100ml using spirometry.
Secondary Outcome Measures
- The identification of exacerbation pathogenesis in patients receiving anti-IL5 therapy via cytokine analysis [12 months]
Blood cytokine analysis (analysed by Bio-plex 200 system) will be analysed at ad-hoc exacerbation visits to identify exacerbation pathogenesis.
- The identification of exacerbation pathogenesis in patients receiving anti-IL5 therapy via viral throat swab analysis [12 months]
Viral throat swabs results (using Cepheid Rapid device) will be analysed at ad-hoc exacerbation visits to identify exacerbation pathogenesis.
Eligibility Criteria
Criteria
Inclusion criteria: case participants:
-
Aged 18 - 80 years old
-
Able to give informed consent
-
All patients identified as being suitable for anti-IL5 therapy by the asthma MDT will be considered for study enrolment.
This assessment by the MDT for participants to be eligible includes:
-
A measure of compliance with current asthma medication,
-
Confirmation of asthma diagnosis
-
Suitability for anti-IL5 therapy based on blood eosinophil counts,
-
Asthma exacerbation rates
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Prednisolone dose.
-
Confirmation of treatment requires at least two asthma specialists to agree that this is the correct course of action
-
Patients must first demonstrate over 75% compliance with inhaled and/or oral corticosteroid therapy
The asthma MDT and difficult asthma clinic normally assess patients between 18-80 years so only patients in this age range will be approached.
All patients will be able to give informed consent for study participation.
Exclusion criteria: case participants:
• Pregnancy
Inclusion criteria: control participants:
-
Aged between 18-80 years old.
-
Able to give informed consent
Exclusion criteria: control participants:
-
Pregnancy
-
Underlying respiratory conditions
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Nottingham Respiratory BRU | Nottingham | United Kingdom | NG51PB |
Sponsors and Collaborators
- University of Nottingham
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 18048