Case Introduction

A 33-year-old woman presents to your office for follow-up asthma care. At her initial visit 4 months earlier, she reported a lifelong history of asthma that manifested in childhood. As she got older her asthma worsened with increased frequency of emergency department visits despite use of her maintenance medications. Upon moving to your city several years ago, she noted some initial improvement in her asthma and weaned herself off all of her asthma medications. However, as time progressed, she noted worsening of her asthma control, which required the use of oral steroids several times each year. She reported that over the past year, she has experienced increased frequency of shortness of breath, inability to take a deep breath, and a dry nocturnal cough; she has also reported using albuterol several times per day for exercise-induced breathing difficulty. She has been treated with oral steroids on 6 occasions for management for acute asthma exacerbations.

The patient denied history of intubation. Her asthma triggers include exposure to dust, dogs, cats, and fragrance. She has implemented allergen avoidance measures — including the use of dust mite encasements, regularly vacuuming, and frequently changing her home’s heating and cooling air filter — in an attempt to improve her asthma. She has no pets in her home. Her asthma control test (ACT) score was 15, indicative of poorly controlled asthma. Spirometry did not reveal airflow obstruction (forced expiratory volume in first second of expiration [FEV1]: 2.24 L; 77% predicted) and fractional exhaled nitric oxide (FeNO) was mildly increased at 36 ppb.

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At that time, the patient was advised to resume use of budesonide-formoterol 640/18 mcg/d and montelukast 10 mg/d, as well as to continue using albuterol as needed. Allergy skin testing was deferred in the setting of uncontrolled asthma; instead, the patient underwent laboratory testing that revealed total immunoglobulin (Ig) E to be elevated at 164 IU/L. Specific IgE immunoassays for aeroallergens was notable for sensitivity to cat, dog, Dermatophagoides farinae and Dermatophagoides pteronyssinus. Complete blood cell count revealed no eosinophilia.

At the current office visit, 4 months after her initial visit, the patient reports that she is improved with the recommended regimen but is still not back to her baseline as she continues to have daytime shortness of breath, nocturnal cough 3 to 4 nights per week, and chest tightness with minimal activity. She reports that she continues to require use of albuterol 3 to 5 times per week and has required 2 courses of oral steroids prescribed by her primary care physician.

What would be the next best step in improving this patient’s asthma control?

Omalizumab for Moderate to Severe, Poorly Controlled Allergic Asthma

Omalizumab is a recombinant humanized IgG1 k antibody that binds to the Fc region of IgE and prevents it from binding to the type 1 high-affinity IgE receptor (FcεR1) on mast cells and basophils.1 As omalizumab competes for the same region of the IgE molecule that interacts with IgE receptors on effector cells (Cε3 domain), it cannot cross-link FcεRI receptors and activate effector cells.2 IgE plays a crucial role in the pathophysiology of allergic asthma. Type I (IgE-mediated) hypersensitivity reactions occur as a result of an allergen cross-linking to IgE bound to FcεRI cell surface receptors.2 As a result of allergen cross-linking, mast cells and basophils are induced to degranulate with release of preformed allergic mediators (histamine, leukotrienes, prostaglandins, chemokines) inducing the early-phase allergic reaction, and production and secretion of proinflammatory cytokines and arachidonic acid metabolites inducing the late-phase allergic response with inflammatory cellular infiltrate.2,3 Given the blockade induced by omalizumab binding free IgE, FcεRI expression on the surface of mast cells and basophils is downregulated and thus allergic response is inhibited.3 Omalizumab reduces free IgE by 89% to 99% soon after administration, and low levels persist throughout treatment.4,5 Although there is reduction in free IgE levels, total IgE levels increase after the first injection as a result of IgE:omalizumab immune complex formation and may remain elevated up to 1 year after medication discontinuation.1 Re-testing IgE levels during treatment with omalizumab is not recommended.1

Omalizumab is available in 2 formulations: a lyophilized powder requiring in-office reconstitution with sterile water and a prefilled syringe.1 Both forms should be administered by a healthcare professional skilled in the management of allergic reactions and anaphylaxis.1 Omalizumab is not indicated for the treatment of acute bronchospasm or status asthmaticus.1 Response to treatment with omalizumab may take several weeks.1 

Treatment with omalizumab should be considered for patients aged ≥6 years with uncontrolled, moderate to severe, persistent asthma (Global Initiative for Asthma [GINA] 2019 Step 5, National Asthma Education and Prevention Program Expert Panel Report 3 [NAEPP EPR3] Step 5/6) and with a history of positive skin test or in vitro reactivity to a perennial aeroallergen.1,6-9 Total serum IgE should be measured in all patients for whom omalizumab therapy is being considered as dosage is based on patient’s weight (kg) and total pretreatment serum IgE (IU/mL), as per the manufacturer’s guidelines.1

Results from 2 pivotal phase 3 trials published in 2001 revealed the effect of omalizumab in patients aged 12 to 75 years with uncontrolled asthma despite treatment with medium- to high-dose inhaled steroids.4,5 As a result of findings from these studies, omalizumab was approved for use by the US Food and Drug Administration.10 Both studies included a 4-month stable steroid phase followed by a several-month phase of steroid reduction.4,5 In these studies, treatment with omalizumab resulted in fewer asthma exacerbations per patient and lower percentages of individuals experiencing exacerbations compared with placebo during the stable steroid phase and during the steroid reduction phase.4,5 In both studies, patients treated with omalizumab experienced improvement in baseline FEV1 and were able to tolerate a greater reduction in dose of inhaled beclomethasone compared with those receiving placebo; in addition, there was noted to be a greater likelihood of beclomethasone discontinuation in the omalizumab treatment groups.4,5

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The standard of asthma care has evolved with current guidelines now recommending the use of a high-dose inhaled corticosteroid in combination with a long-acting β-2 agonist (ICS-LABA) in those with uncontrolled severe asthma.8,9 Benefit of omalizumab has been documented in patients with severe asthma that has been inadequately controlled with the use of high-dose ICS-LABA, with an approximate reduction in exacerbation frequency of 25% to 26% compared with placebo and notable improvement in asthma symptom scores and asthma-related quality of life.6,7 Additionally, the INNOVATE trial ( Identifier: NCT00046748) documented a 100-mL gain in baseline FEV1 in patients treated with omalizumab in addition to ICS-LABA compared with those treated with ICS-LABA plus placebo.6