Pilot Observational Study Utilising MRI to Study Mepolizumab in COPD
Research type
Research Study
Full title
A pilot Study of the Use of 129Xe and 1H MRI to measure the Modulation of Eosinophil-Related inflammation by mepolizumab In COPD (SUMMER)
IRAS ID
1003843
Contact name
Rod Lawson
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Eudract number
2021-002901-84
Clinicaltrials.gov Identifier
Research summary
COPD is the name for smoking related lung disease, which includes bronchitis and emphysema. Those who suffer from this disease get daily symptoms like cough, phlegm and breathlessness. Occasionally this worsens for various reasons, these flare ups are called exacerbations. During an exacerbation people often need treatment with steroids and antibiotics, and sometimes needing admission to hospital. People with lots of exacerbations are more likely to get other health problems, and their lungs get worse more rapidly. Some treatments exist to lessen the chances of an exacerbation, but they only reduce this by one third.
People with asthma also get exacerbations. There are a new range of treatments, including a drug called mepolizumab which is good at preventing exacerbations in asthmatics. Some with COPD have 'asthmatic' type inflammation. Research shows mepolizumab may reduce exacerbations of people with COPD and asthmatic inflammation but further research is needed to show us more clearly who is likely to benefit from the drug.
To gain this understanding we need to be able to measure inflammation within the body. We have developed a way to use an MRI scanner to do this using xenon gas to give us good pictures of the lungs. We can then measure how xenon flows within the air spaces of the lungs, and from there to the blood. This tells us a lot of detail about inflammation and damage in the lung.
We aim to find participants with COPD with 'asthmatic' type inflammation, and treat them for a year with mepolizumab. We will take scans before the treatment, after 12 weeks and after a year to see how the drug affects inflammation. We will also compare our measurements with the number of exacerbations people get, with measures of their quality of life, and with ordinary laboratory breathing tests. We are especially interested to know if the reduction in inflammation early on after 12 weeks is associated with fewer exacerbations and better quality of life over the year.Results Summary
In recent years the treatment of asthma has been transformed by a range of drugs called ‘biologics’ which block specific parts of inflammation. The sort of inflammation that they block (called eosinophilic inflammation) can also be found in some people who have COPD (smoking related lung disease). Some clinical research has suggested that the biologics may be helpful in these people but the effect is not as dramatic as in COPD. We wanted to learn more about this, to see if we can find particular people the drugs might help, and to find ways to design better drugs in the future.Participants in the research were those who had COPD with eosinophilic inflammation, who had also suffered from flare ups in the past. We think the biologics may have a particular role in reducing flare ups.
To measure inflammation in the lungs we used MRI scanning. Usual MRI scanners don’t produce good pictures of the lungs so we used an advanced technique called Xenon MRI scanning. This is where participants inhale Xenon gas and we can see where it goes using the MRI scanner. Sheffield is one of a limited number of centres in the world with the skills, experience and technology to carry this out.
In the main part of the study we carried out scans before and after 12 weeks of treatment with mepolizumab. This was given by injection on a monthly basis. The two main things measure were how easily the air could flow into the lungs, and which part of the lungs it reached (ventilation), and how easily gas got from the airspaces to the tissue in the lungs. Gas should move easily from the airspaces to the tissue, but inflammation may interfere with this. On average neither of these main measures changed after mepolizumab treatment.
We know from previous research that the ventilation measurement may change a lot after mepolizumab in people with asthma. We also know that this measurement may change after other drug treatments in COPD. Thus our results suggest that eosinophilic inflammation in COPD may be different in some way to that in asthma and that there may be a need to develop different approaches for COPD.
Our main measure of ventilation was used what is regarded as the standard approach for analysing MRI scans. However, we also use another approach called treatment response mapping (TRM). This did improve after mepolizumab. It is useful to know that this technique seems to be more sensitive, and it can be used in future research to give more precise information.
We also carried out a lot of breathing and other tests to see if they gave extra information. Usually when doctors assess the amount of eosinophilic inflammation (the type we think mepolizumab might treat) they do a blood test to measure the amount of eosinophils in the blood. We did not find that those with a higher blood eosinophil count had any different change in ventilation according to the MRI scans.
A breathing test called FeNO was also carried out. This is often used in asthma to guide treatment, but it is usually thought not to be so useful in COPD. Interestingly we found the higher a participant’s FeNO was before treatment, the more likely their ventilation was to improve on the MRI scan. This suggests more attention should be given to this measurement in future research, particularly as it is very easy to carry out.
Some participants continued in the study for 12 months and had further scans at the end. In these participants we also recorded the number of flare ups they had during that time. People who did not have many flare ups were no more likely to have a change in their MRI in response to treatment than those who had a lot of flare ups; in other words we could not relate a change in response to treatment in the short term using our scans to how things worked out for the participant over the course of the year.
In some ways the results appear disappointing as we have not shown a clear measurement relating to the drug as such or a way to use scans to predict who might benefit longer term. However, by demonstrating there does appear to be a difference from asthma this highlights the importance of being clear in future research of the mechanisms and treatments of each. Both are important conditions, but this research highlights the importance of distinguishing clearly between the two. There has been a tendency to think of those with eosinophilic asthma to be like those with eosinophilic COPD but our research suggests it may not be so simple. Our demonstration of the increased sensitivity to change of TRM in MRI will be important in planning future research and getting the maximum information from the data the scans provide. The finding that FeNO may be predict response suggests further research into this test is appropriate in COPD. As it is available in all chest clinics and simply involves blowing into a tube it has the potential to be easily used as a routine if further research clarifies this.
REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
22/NW/0009
Date of REC Opinion
22 Feb 2022
REC opinion
Further Information Favourable Opinion