Introduction
Chronic rhinosinusitis (CRS) is a disease caused by inflammation in the sinuses. The treatment of CRS is with steroids. Steroids reduce inflammation. They can be delivered into the nose or taken by the mouth. While oral steroids are helpful, they do have side effects. Doctors and researchers are working to make new ways to treat CRS with less side effects.
Biologic medications (biologics) target certain cells or inflammation elements linked with a disease. Biologics are thought to have less side effects and be more effective than steroids. They have been studied for other diseases. They can control inflammation in Asthma. They are being studied to know their safety and efficacy in CRS.
Here we will discuss biologics for CRS. We will also explain how they work.
Inflammation in Chronic Rhinosinusitis
There are two different forms of inflammation in CRS. One is without nasal polyps (CRSsNP) and the other is with nasal polyps (CRSwNP). The only biologics studied for CRS are the ones that have polyps.
CRSwNP is caused by white blood cells called type 2 T-helper cell (Th2 cell). They can make proteins called interleukins (IL). These proteins help white blood cells talk to each other. These proteins also increase inflammation. There are different types of interleukins. Interleukins IL-4, IL-5, IL-10, IL-13 are increased in Th2 inflammation. IL also activate another type of white blood cell called Eosinophils. They are the result of this type of inflammation. Eosinophils are also found in asthma and allergy. Eosinophils communicate with immunoglobulin E (IgE). IgE is increased in patients with nasal polyps and allergies.
Three molecules have been studied for biologic therapies in CRSwNP. These are IL-5, IL-4, and IgE. The drugs investigated for these will be discussed below.
Anti-Interleukin-5 (IL-5) Therapy
IL-5 is one of the molecules seen in CRSwNP. IL-5 is often high in patients with nasal polyps. IL-5 turns on eosinophils in Th2 inflammation. Lowering IL-5 may prevent eosinophil activation. Less IL-5 means less inflammation. Drugs to treat IL-5 are reslizumab and mepolizumab. Benralizumab is a similar medication that targets the IL-5 receptor. These drugs are antibodies that block the effects of IL-5. Once in the body, they find their target and turn it off.
These medications are under research. This will tell us how safe and good they are for CRSwNP. These biologics have been studied in small number of patients (24 to 30 patients) in short time (4 weeks). They were found to shrink polyps in the nasal cavity, but they did not improve patients’ symptoms. These results have encouraged doctors to study more these drugs. Medical research are being done in larger groups and for longer time. As the results become available, they will help doctors decide if these drugs should be used in CRSwNP.
Anti-Interleukin-4 (IL-4) And (IL-13) Therapy
IL-4 and IL-13 are other proteins being studied in CRSwNP. IL-4 and IL-13 may play an important role in the activation of cells to form polyps in the nasal cavity. Blocking this proteins is by the use of antibodies. An antibody finds a receptor and blocks it. The medication that has been developed to treat IL-4 is also an antibody. Blocking this receptor stops IL-13 from delivering its inflammatory message too.
Dupilumab is an IL-4 receptor antibody. It was created to treat patients with atopic dermatitis. Atopic dermatitis is an allergic-like inflammation of the skin. A study examined its effects in CRSwNP. It looked the effects of the drug on 60 patients for 16 weeks. The doctors found smaller polyp size and improvement in symptoms. At this time, this is the only biologic therapy that has been shown to do both.
Anti-IgE Therapy
Immunoglobulin E (IgE) is high in patients with CRSwNP. Eosinophils are elevated when IgE is high. Drugs to reduce the level of IgE are used to treat problems with high eosinophils count.
Omalizumab is an antibody that stops IgE function by blocking its receptor. Two studies have looked at the effects of omalizumab in CRSwNP. These were both small studies (14 and 24 patients) over 16-24 weeks. They saw smaller inflammation on computed tomography scans (CT). One saw reduction in polyp size. No study saw improvement in patient symptoms. Studies are still going on this drug.
Benefits of Biologic Therapies
There are scientists testing the new biologic medicine. They have found that they likely work well. Biologics can reduce the swelling from polyps. Also help you avoid steroid pills. People that use this medicine usually need less steroid pills than people who do not use this medicine. They may need less sinus surgery. This new medicine can help people avoid the side effects from other medicines and surgery.
Risks of Biologic Therapies
Serious complications happen for less than 1 in 100 people. Some people have an allergy to the medicine. This can sometimes cause trouble breathing. This can be life threatening. Many people have soreness at the injection site but this usually goes away quickly on its own. This happens in 1 in 10 or 1 in 2 people depending on the study. Some people can also have headaches with this medicine. This happens to 1 in 20 to 1 in 5 people depending on the study. Rarely, some people have a herpes flare up. This happens in 1 in 25 to 1 in 12 people who have a history of herpes or cold sores. One in 10 people who use dupilumab had eye pain and swelling. People who took Omalizumab had increased risk of heart problems. Three out of one hundred people had a heart attack or blood clot in their lungs while taking the medicine. There is also a small chance of getting sick more often with things like the cold or flu.
There was a concern for having cancer in patients taking omalizumab. There is no increased risk for cancer over 9 years. This is based on studies in asthma patients.
Summary
Biologic medications are used to control inflammation in CRS. They are still under investigation. Biologics can be an option for CRSwNP. There is new research on different biologic medications. More studies on the risks and benefits is needed before they can be used in routine. Overall, biologics may be a useful and safe alternative to current therapies.
Copyright © 2020 by the American Rhinologic Society