Revolutionary new treatment set to transform lives of severe asthma sufferers

  

Patients with severe asthma have symptoms that negatively affect their quality of life, despite daily therapy with corticosteroids delivered through an inhaler, and frequently seek medical help due to their condition.  

Over the last two decades, studies into the biology of severe asthma carried out by a global team led by Professor Brightling at the NIHR Leicester BRC have led to a number of antibody-based therapies which have revolutionised management of the serious condition.   

Professor Brightling, Clinical Professor of Respiratory Medicine at the University of Leicester, said: “Our focus has been on understanding the biological processes that lead to inflammation and mucus building up in the lungs of people with severe asthma; what causes this, and how we could potentially stop it.”   

On looking closely at the genetics and lung tissue samples of people with severe asthma, the Leicester researchers were the first to recognise that a substance called thymic stromal lymphopoietin (TSLP) increases the risk of someone having severe asthma and is closely involved in the inflammation in the airway in asthma.  

The 'biologic' monoclonal antibody, tezepelumab which is given as a monthly injection, specifically targets TSLP.  

In the initial clinical studies (published in 2021 and 2023) tezepelumab, which has been commercialised in the UK by AstraZeneca, reduced asthma attacks by more than 50%. Not only that but the number of attacks which led to hospitalisation reduced by over 80% with participants showing improvement in inflammation and breathing tests.   

Now, the latest research has shown in CT scans of the chest that tezepelumab reduces the number of airways that are plugged or blocked by mucus. This improvement in mucus plugging was linked to improvements in inflammation and lung function.   

In the trial, published in September 2023, in the New England Journal of Medicine: Evidence, 82 participants had CT scans to observe mucus plugs at week zero and week 28.  

Thirty-seven participants were given tezepelumab after the first scan, and once every 4 weeks for the duration of the study. The remaining participants were given a placebo. 

Researchers found that mucus plugs were present in 57% of patients before they were treated with tezepelumab which reduced to 22% of patients after treatment.  

The proportion of patients with mucus plugs who received the placebo did not change significantly (mucus plugs were present in 31% of patients before receiving a placebo, and in 33% of patients after receiving placebo).   

Reductions in mucus plug scores with tezepelumab were also associated with improvements in lung function and inflammation.  

David Chapman, age 57 from Groby in Leicestershire, was first diagnosed with asthma in 2004, after becoming increasingly breathless on his regular mountain bike rides, and suffering from frequent chest infections.  

A short time after being referred to Glenfield Hospital, David was asked if he would be interested in taking part in some respiratory research at the NIHR Leicester Biomedical Research Centre (BRC). 

David said: “I was really dependent on my inhaler. Every time I left the house it was ‘keys, wallet, phone, inhaler’. I couldn’t be without it, so I was really keen on taking part in research if it would help find another treatment.  

“After three to four days of being on the trial I found I wasn’t touching my inhaler at all in the day. Obviously, I didn’t know for sure if I was taking the new medicine, or if I was on the placebo, but I was pretty convinced I was by how well I felt.  

“It was a complete game-changer. I had much more energy, I did lots more walking with my dog and felt great.” 

Tezepelumab has now been approved by NICE for use in the UK as an adjunctive treatment for severe asthma in individuals aged 12 years and over, when treatment with high-dose inhaled corticosteroids plus another maintenance treatment has not worked well enough.   

“It’s fantastic news,” David said. 

“It made a huge difference to my quality of life, and I’m sure it will for other asthma patients too. I’m hopeful that I will be able to receive the medicine in the clinic soon and feel as well as I did when I was on the trial.”  

Professor Brightling added: “As an NIHR Biomedical Research Centre, our mission is to take findings from the laboratory and deliver them into new treatments for patients. To see this new medicine come full circle and be prescribed in our severe asthma clinic based at Glenfield Hospital, where this research programme started, is incredibly special.”  

“Being able to tell patients like David that there is an alternative to daily management with an inhaler is what we aspired to do, and seeing that happen is truly wonderful.”