Biologics and eosinophilic asthma
What is eosinophilic asthma?
Eosinophilic asthma (EA) is a severe disease involving a type of white blood cell called eosinophils. These immune cells work by releasing toxic chemicals that kill harmful pathogens. During infection, they also help to stimulate inflammation which allows for other immune cells to be delivered to the area to repair it. However, in people with EA these eosinophils become unregulated and cause excess inflammation of the airways and respiratory system, leading to the asthmatic symptoms. Therefore, in EA treatments, the aim is to reduce the levels of eosinophils in the body.
Find out more about EA here – https://www.healthline.com/health/eosinophilic-asthma
Biologics are a specialist type of medication (monoclonal antibodies) given by injection only and are currently in development to treat a variety of illnesses where our immune systems play a part eg asthma and cancer. They are produced from natural living organisms such as humans, animals and microorganisms and they include a range of products like vaccines, blood, tissues and gene cell therapies.
More on monoclonal antibodies – https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/monoclonal-antibodies.html
More on biologics – https://www.bioanalysis-zone.com/biologics-definition-applications/
They are more targeted than other asthma treatments such as steroids because they are aimed at one specific part of the immune system, reducing side effects. Biologics are taken in combination with steroids, but the dose of steroid needed is significantly reduced (consequently steroid-induced side effects are also reduced).
There are currently 5 types of biologics available. These are:
The first two on this list (reslizumab and mepolizumab) work in a similar way. They target the cell that activates eosinophils; this cell is a small protein called interleukin-5 (IL-5). If IL-5 is stopped from working, then eosinophil activation is also prevented and inflammation reduces.
Benralizumab also targets eosinophils but in a different way. It binds to them which attracts other natural immune killer cells in the blood to come and destroy the eosinophil. This drug pathway more strongly reduces/eliminates eosinophils compared with reslizumab and mepolizumab.
Omalizumab targets an antibody called IgE. IgE stimulates the activation of other inflammatory cells to release chemicals such as histamine as part of an allergic response. This response results in inflammation within the airways and triggers asthmatic symptoms. An allergy to aspergillus can set off this pathway, meaning patients with ABPA often have EA. Omalizumab can block this allergic response and hence reduce the subsequent asthmatic symptoms.
The final biologic, dupilumab, is also recommended for people with severe asthma associated with allergy. It works by blocking the production of two proteins called IL-13 and IL-4. These proteins trigger an inflammatory response which leads to mucus production and IgE production. Again, once these two proteins are blocked, inflammation will reduce.
For more information on these drugs, visit the asthma UK website – https://www.asthma.org.uk/advice/severe-asthma/treating-severe-asthma/biologic-therapies/
Crucially, there is a new biologic drug on the market called Tezepelumab. This drug acts much higher up in the inflammation pathway by targeting a molecule called TSLP. TSLP is essential in many aspects of the inflammatory response and has a wide range of effects. This means that all of the targets (allergic and eosinophilic) of the currently available biologics are covered in this one drug. In a recent trial conducted over one year, Tezepelumab (in combination with corticosteroids) achieved a 56% reduction in asthma exacerbation rate. This drug is up for approval by the FDA in the first quarter of 2022. Once it is approved, it will be accessible as part of clinical trials or via case-by-case funding from clinical commissioning groups, however it won’t be available on the NHS until it is approved by NICE. Nevertheless, Tezepelumab provides hope on the horizon for people suffering with EA.
Unfortunately, not all of these drugs are easily accessible in the UK and to be prescribed the patient must meet strict criteria from the National Institute for Health and Care Excellence (NICE). To be given biologics, you must be adhering to your current treatment plan and taking your medication properly. These biologics are available from specialist clinics such as the North West Lung Centre in Wythenshawe Hospital, Manchester who assess a patient and apply for funding for initiation of the drug if they are eligible.
Please refer to the NICE guidelines for the drugs that are currently available below:
- Reslizumab – https://www.nice.org.uk/guidance/ta479/chapter/1-Recommendations
- Mepolizumab – https://www.nice.org.uk/guidance/ta671/chapter/1-Recommendations
- Benralizumab – https://www.nice.org.uk/guidance/ta565/chapter/1-Recommendations
- Omalizumab – https://www.nice.org.uk/guidance/ta278/chapter/1-Guidance
If you have been taking steroid treatment that is not effective and you feel that you could benefit from these drugs, speak to your respiratory consultant.