27 Biologics
27.1 Introduction to Biologics
Allergic disorders including atopic dermatitis (AD) and asthma have a high prevalence, but even with prevailing available therapies, many patients continue to have uncontrolled symptoms. Although some patients present with similar clinical symptoms, the drivers of their disease processes can be different. This has brought the concept of endotyping to the forefront of our understanding of these diseases. An endotype is a subclassification of a particular disease that is based on a particular pathophysiologic mechanism and associated clinical biomarkers. Targeted therapies are available based on specific endotypes. There are two inflammatory pathways that drive allergic disease: Type 2 (Th2) inflammation and non-type 2 inflammation. All of the biologics currently approved for use focus on the Th-2 inflammatory pathway. Targets along this pathway include anti-interleukin (IL)-5, anti-immunoglobulin E (IgE), anti-IL-4, and anti-IL-13. This chapter also reviews the current use of biologics in allergic disorders. See ▶Table 27.1 for a summary of trials using monoclonal antibodies.
27.2 Immunoglobulin E
27.2.1 Omalizumab
Omalizumab targets circulating IgE. In 2003, omalizumab became the first Food and Drug Administration (FDA)-approved biologic for use in moderate to severe asthma. Mast cells and basophils have high-affinity IgE receptors (FcεR1) on them. Omalizumab is a recombinant humanized anti-IgE antibody that blocks IgE from binding to these high-affinity receptors, thus blunting the allergic response that would be driven by the release of histamines, prostaglandins, leukotrienes, and other mediators.
Omalizumab was first approved for use in adults and adolescents (12 years of age and above) with moderate to severe persistent asthma. The large trials showed that omalizumab reduced asthma exacerbations. Patients in the studies had a serum IgE level between 30 and 700 IU/mL and a positive skin test or in vitro reactivity to a perennial aeroallergen. In 2016, it became approved for children aged between 6 and 12 years for uncontrolled moderate- to severe-persistent allergic asthma.
In 2014, the FDA-approved omalizumab for the indication of chronic idiopathic urticaria (CIU) in patients aged 12 years and up who remain symptomatic despite treatment with antihistamines.
Omalizumab was found to improve nasal symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). However, this was only studied in CRSwNP patients who also had comorbid asthma. Phase III studies are currently underway investigating use in CRSwNP subjects.
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