WAYFINDER trial of tezepelumab monthly injection shows oral steroid reduction for most severe asthma

The international WAYFINDER trial – led by King’s College London – has shown that for severe asthma patients the use of Tezepelumab, a biologic antibody, reduces patient’s use of daily oral steroids while maintaining control of symptoms

A large international clinical trial of a monthly antibody injection has enabled almost 90% of people with severe asthma to cut their daily steroid tablets with more than half able to entirely stop oral steroids without loss of symptom control.

The WAYFINDER study, led by King’s College London has evaluated the monoclonal antibody tezepelumab in patients with severe, steroid-dependent asthma. Tezepelumab is an injectable biologic therapy that targets key immune pathways involved in airway inflammation. By blocking these upstream signals, the drug reduces inflammation in the lungs and aims to control asthma without the long-term harms associated with oral corticosteroids.

In the trial, patients with a confirmed diagnosis of severe asthma received tezepelumab every four weeks for a year. Participants had been recruited from 68 clinical centres across 11 countries, which reflects real-world practice in specialist asthma services. All patients completed detailed questionnaires on their symptoms and medication use at 28 and 52 weeks to allow investigators to track changes in steroid dose, lung function and day-to-day impact.

Treatment with tezepelumab led to a marked reduction in reliance on oral steroid tablets. Almost 90% of participants were able to reduce their daily dose and more than half discontinued oral steroids altogether while maintaining stable asthma control. These reductions occurred in parallel with significant improvements in symptom scores, lung function tests and measures of overall quality of life.

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Two-thirds of patients had no asthma attacks during the study period which suggests a substantial effect on exacerbation risk. Investigators reported that benefits emerged as early as two weeks after the first injection and persisted throughout the 52-week trial.

Severe asthma affects a relatively small proportion of people with asthma but accounts for a disproportionate share of hospital admissions and healthcare costs. Many of these patients depend on long-term oral corticosteroids to prevent life-threatening attacks. However, chronic steroid exposure is linked to serious complications, including osteoporosis, type 2 diabetes, weight gain, high blood pressure and a greater vulnerability to infections. Clinicians have therefore sought alternative ways to control inflammation in severe asthma that do not carry the same systemic burden.

The WAYFINDER trial forms part of a long-running programme of research into severe asthma at King’s College London. Last year, a separate team at King’s reported that the monoclonal antibody benralizumab could be administered during some asthma and chronic obstructive pulmonary disease (COPD) attacks to reduce the need for further treatment. The tezepelumab findings suggest that antibody-based therapies now have potential to treat acute attacks and offer long-term management of severe asthma.

“The WAYFINDER study is an important step forward for patients with the most severe form of asthma who require daily oral steroids in order to achieve reasonable disease control,” said Professor David Jackson, who is the clinical professor of respiratory immunology at King’s College London and clinical lead of the asthma services across Guy’s and Royal Brompton Hospitals at Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust.

“In this international, multicentre clinical trial of more than 300 patients, the National Institute for Health and Care Excellence (NICE)-approved asthma treatment tezepelumab, a biologic therapy that targets asthma-related inflammation but without all the side effects of steroids, was capable of allowing the vast majority of patients to wean their steroids down to a low dose with more than half able to stop their steroids altogether.

“As tezepelumab also suppresses allergy related symptoms and improves chronic rhinosinusitis as well, the results are particularly exciting for patients with severe asthma who suffer with both upper and lower airway symptoms,” he added.

The trial has also attracted strong support from patient organisations such as Asthma + Lung UK.

“This study is a promising sign that tezepelumab injections support certain people with severe asthma to reduce or stop taking steroid tablets, which can have serious unwanted health consequences. Tezepelumab, an injectable biologic, significantly improves asthma symptoms, lung function and overall quality of life for participants,” said Dr Samantha Walker, Director of Research and Innovation at Asthma + Lung UK, said.

“This is an incredibly encouraging development for the future of asthma care that could transform the lives of people with severe asthma. It’s vital that research into novel types of treatment continues but we know current funding for lung health research is on life-support, despite lung conditions remaining the third biggest cause of death in the United Kingdom. Studies like this show the positive impact that research can make on providing potentially life-changing treatment for people with asthma and other lung conditions,” she added.

The authors of the WAYFINDER study have argued that their findings support wider use of tezepelumab in appropriate patients with severe, steroid-dependent asthma. If healthcare systems adopt this approach at scale, specialists hope that the burden of long-term steroid toxicity could fall, with patients benefitting from disease control and a better quality of life.

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