Biologics in Chronic Rhinosinusitis: An Update and Thoughts for Future Directions

Abstract

Background Potential biologic therapies for chronic rhinosinusitis (CRS) is a growing field of interest and research. Biologics target specific immune cells or inflammatory pathways within a disease process, increasing drug efficacy while reducing complications. The success of biologics in other inflammatory conditions such as asthma and atopic dermatitis has spurred much of the corresponding research in CRS. A rapid expansion in the volume of research concerning biologic therapies with potential crossover to treating CRS has made it difficult to stay current. Furthermore, much of the literature has been focused on allergy, asthma, and immunology subspecialties. As the role for biologic therapies in CRS continues to expand, it is increasingly important for otolaryngologists to remain up to date on their progression. Objective The objectives of this review are to provide an update on the growing field of biologics for otolaryngologists who treat CRS and discuss potential future areas of research. Methods A literature review of biologic therapies studied in CRS was performed. In addition, a detailed review of all biologic therapies targeting inflammatory markers involved in Th1-, Th2-, and Th17-mediated inflammation was performed to identify potential areas for future research. The role for biologic therapies in CRS, endotypes of CRS, current biologic therapies studies in CRS, and future areas for research were reviewed. Results Sixty-nine unique biologic therapies have been developed for Th1-, Th2-, and Th17-mediated inflammation. Five biologics are currently being investigated for use in patients with CRS with nasal polyposis. Conclusions As the field of biologics continues to expand, remaining up to date on the current literature may help clinicians identify patients who may benefit from biologic therapies. In addition, ongoing research in other inflammatory disorders with shared pathophysiology to CRS may reveal other potential therapies for CRS that have not previously been investigated.

The use of biologics in children with allergic rhinitis and chronic rhinosinusitis: Current updates

“…In that same study it also improved both olfactory and disease‐specific quality of life questionnaire scores, more so than mometasone spray alone . Siglec‐8, a new biologic agent which acts on a receptor found in mature eosinophils is under investigations . The binding of antibody by siglec‐8 will induce apoptosis cytokine‐activated eosinophils and prevention of release of mediators from mast cell …”

“…The anti‐IgE monoclonal antibody omalizumab binds to high‐affinity IgE Fc receptor in interstitial fluid and blood, thus blocking the IgE‐mediated inflammatory cascade and eventually reducing the concentration of free IgE in serum which in turn results in reduced binding of IgE to mast cells and basophils . The IL‐5 pathway functions by activating Th2 cells, leading to the release of IL‐5, which in turn leads to increased IgE, eosinophilia, chemotaxis, differentiation, activation, and eosinophil survival . In the IL‐4/IL‐13 pathways inhibitors activate cytokines that lead to Th2 cell differentiation and activate a type 2 inflammatory response via IgE synthesis and eosinophils, basophils, and mast cell production .…”

“…There are significant costs associated with the use of biologics. Direct costs have been estimated to range from approximately $10 000 to $40 000 annually . The use of biologics may be justified in patients with life‐threatening conditions such as severe allergic asthma with frequent intensive care unit admissions and frequent visits to the emergency room requiring nebulizer therapy.…”

“…As the approach is relatively new, the safety profile of biologics is not fully understood. Apart from common adverse effects such as localized injection site reactions (8%–45%) and headaches (6%–19%) as well as associations with herpes simplex reactivation, conjunctivitis, and a risk of serum sickness, more serious complications have been reported . Anaphylaxis and hypersensitivity reactions have been reported in 1% of patients .…”

“…Current recommendations include monitoring patients for 2 hours after each of the first 3 three doses, and a 30‐minute observation period after the administration of every subsequent doses . Omalizumab administration has also been associated with cardiovascular complications such as pulmonary embolism, deep vein thrombosis, myocardial infarction, and unstable angina, as well as malignancy . In addition to the need to be vigilantly aware of the potential complications and monitor the patient accordingly, there is a requirement for frequent monitoring of body weight and IgE levels, and appropriate adjustment of dosage and frequency based on those parameters.…”