Criteria for Changing Biologics

I was having a conversation recently with another asthmatic about the number of patients we know who have changed or are switching biologics. While every patient is different, it seemed like we each knew a few people to seemed to be making changes. This had me thinking about my own journey with biologics and what criteria physicians were using to determine when a change may need to be made.

What are the criteria for biologics usage?

The criteria that are used to establish when a biologic is prescribed are outlined by a number of different respiratory societies and guidelines. These include the holy grail, the Global Initiative For Asthma (GINA) guidelines, as well as the American Thoracic Society (ATS) guidelines, European Respiratory Society (ERS) guidelines, and many more specific country guidelines.

One primary consideration for beginning biologic usage is the diagnosis of severe persistent asthma.¹ Severe persistent asthma is defined as being uncontrolled despite adherence to maximum therapies and the treatment of contributing factors.²

It is also important to note that severe asthma differs from difficult-to-treat asthma, which is defined by GINA as asthma that remains uncontrolled despite GINA step 4 or step 5 treatment (medium- or high-dose inhaled corticosteroids with a second controller).² Difficult-to-treat asthma is still difficult to treat in the absence of changeable factors such as incorrect inhaler technique, poor adherence, comorbidities, or incorrect diagnosis.

How do physicians know which ones to choose?

There are currently limited studies that have made direct comparisons of biologics. Current methodologies include looking at biomarkers and phenotypes. Asthma is classified as Th2-high or Th2-low. Some people refer to these 2 types as type 2 and non-type 2. Type 2 refers to specific immune T cells called T helper 2 cells that drive allergic inflammation or disease. Approved biologics for asthma treatments include anti-serum immunoglobulin E (IgE) (omalizumab), anti-IL-5 (mepolizumab, resilizumab), anti-IL-5 receptor (benralizumab), and anti-IL-4 (dupilumab). A few major categories and their possible biologic considerations are:^1-4

Th2-high: allergic asthma with eosinophilia

• Biomarkers: high IgE, eosinophils, and exhaled nitric oxide
• Biologic Therapies: anti-IgE (omalizumab), anti-IL-5 (mepolizumab), and anti-IL-4 (dupilumab)⁴

Th2-high: non-allergic, eosinophilic asthma

• Biomarkers: blood eosinophils higher than 300 μl/L, normal IgE, and exhaled nitric oxide
• Biologic therapies: anti-IL-5 (mepolizumab and reslizumab), anti-IL-5 receptor (benralizumab), anti-type 2 lymphocytes (cytokines), and monoclonal antibodies (T2 mAbs)⁴

Th2-low: neutrophilic asthma

• Biomarkers: elevated neutrophils in blood and sputum, various cytokines and chemokines, and neutrophil growth-stimulating factor. Further investigation into this correlation is currently being studied, and further biomarkers are currently being identified.
• Biologic therapies: There are no FDA-approved biologic treatments. These are still in development, and investigations are continuing.⁴

When or why are changes made in therapies?

Each patient is different and has different elements driving their asthma. While your care team may try to match you to therapy, it is possible that it may not be successful. I personally know that this is a hard expectation to manage. We all want to feel better and know that treatments have positive effects. It can also be quite discouraging when treatment may be perceived as failing.

The major reasons that asthma patients may express having therapies changed outside of issues involving insurance coverage are:^2-5

• Patients may not be phenotyped or have asthma characteristics for the specific therapy they are trying. They may be changed to a different therapy if new information comes to light.
• Patients may have comorbidities that have not been addressed or were excluded in diagnosis, leading to asthma control issues. In these cases, patients' comorbidities are addressed, and a biologic may be discontinued. Care teams will guide these decisions and usually in consultation with their patients.
• Asthma immunology undergoes constant investigation and is not fully understood. As researchers discover more about asthma immunology, there will hopefully be more targeted therapies in development.
• A patient may be considered a non-responder or therapy has stopped working or working as well. This can be an incredibly frustrating experience. I felt that this happened to me at the beginning of my biologic experience and I was changed to another one. The rationale for the decision was that another immunological process might have been driving my symptoms. I did have some success with my second biologic, although it was also determined not to be a perfect solution.
• Timing and schedule are other reasons for changing a biologic. The dosing frequency for biologics ranges from every 2 weeks to every 8 weeks. Providers may change a biologic based on a patient's schedule to make sure patients are able to take them on time.
• In general, biologicals are known to be safe with minimal reactions. However, some allergic reactions have been identified.

As more information becomes available to researchers and physicians, we may see better patient alignment to biologics. The available biologics have clinical effect predictors that need to be considered during the assessment process. Unfortunately, high symptom scores or reduced lung function are not enough on their own to merit a switch to biologics.⁵

Have you been switched from one biologic to another? Were you provided with a rationale for the changes? I would love to hear about your experience.