Carefully Consider Biomarkers, Patient Needs When Initiating Biologics for Asthma

With a growing list of biologic options for moderate to severe pediatric asthma, pharmacists must carefully consider relevant biomarkers and patients’ individual needs, according to a presentation at the 2023 Asembia Summit.

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Asthma is a chronic inflammatory disorder of the airways causing variable and recurrent symptoms typically associated with widespread but variable airflow obstruction, according to presenter William C. Anderson III, MD, FAAAAI, FACAAI.

“Obviously, as a patient has more and more severe and persistent asthma, you’re going to notice that their symptoms occur on a more daily basis,” Anderson explained. “But you may have patients with more mild asthma that only occurs occasionally or certain times of the year.”

Uncontrolled moderate-to-severe asthma is characterized by coughing, wheezing, nocturnal wakening, and activity limitation. Clinical findings include airway hyperresponsiveness, bronchoconstriction, airway edema, and Asthma Control Test and Asthma Control Questionnaire scores. Treatments include systemic steroid bursts and increased short-acting beta-agonist use, although emergency department (ED) visits and hospitalizations are unfortunately common.

“You want to see that steroids or albuterol completely relieves their symptoms,” Anderson said. “If you’re continually giving these [treatments], you may want to consider a different diagnosis.”

Asthma has different phenotypes and is characterized as type 1 and type 2. Type 2 asthma is classic, allergic-driven asthma underlaid by the endotypes, or biologic mechanisms. The 3 key endotypes include eosinophils, immunoglobulin E (IgE), and Th2 cells, which are also the target of biologics to disrupt these pathways.

Asthma is categorized as either allergic or nonallergic eosinophilic. Aero allergens are often the cause of exacerbations in allergic eosinophilic asthma, whereas pollutants or microbes are triggers for non-allergic eosinophilic asthma.

Additionally, allergic eosinophilic asthma typically onsets in childhood whereas nonallergic eosinophilic asthma onsets in adulthood. Phenotyping asthma is crucial, as well, according to Anderson.

“Overall, these biomarkers will help predict responses to biologics,” Anderson said. “It also can help direct the next best step in terms of controller therapy. It might show the patients who might be more refractory to treatment, and even in some patients, it might be used to calculate exacerbation risk.”

There are 6 FDA-approved biologics for the management of moderate to severe asthma: omalizumab, mepolizumab, dupilumab, benralizumab, tezepelumab, and reslizumab. The first 3 are approved for children aged 6 years and older; benralizumab and tezepelumab are approved for adolescents aged 12 and older; and reslizumab is approved for adults aged 18 years and older. Anderson noted that although dupilumab is approved for children as young as 6 months in atopic dermatitis, its approval for asthma is for 6 years of age and older.

The presentation also included perspectives from Janelle Nelson, whose son was diagnosed with severe asthma at age 8. After being misdiagnosed with cystic fibrosis, Nelson said it took a long time to find optimal treatments to manage his asthma, resulting in frequent trips to the ED and hospitalizations.

“His symptoms were not well managed, so that made it very challenging,” Nelson said. “We were constantly switching inhalers and trying 4 puffs or 8 puffs…but most things actually didn’t work for Cade.”

Ultimately, Nelson said they decided to try a biologic when he was in the pediatric intensive care unit (PICU) at age 9. After that PICU stay, Nelson said he started treatment with the biologic and was not hospitalized for 5 years.

When selecting the right biologic, Anderson said considerations include clinical outcomes, patient age, biomarkers, adverse effects, comorbidities, insurance coverage and costs, and administration route. A survey of practicing allergists found that 91.6% use eosinophilia as their main decision on whether to pick a biologic, although patients and caregivers may have other priorities. For example, some biologics may be able to treat multiple conditions at once, such as omalizumab to treat chronic urticaria as well as chronic rhinosinusitis with nasal polyps.

Regardless of which biologic is ideal, all of the approved treatments have significant barriers, noted presenter Elizabeth Autry, PharmD, BCPPS. In addition to the biomarkers and clinical considerations, she said it is important to think through the patient and provider considerations.

One study found that patients’ top priorities are out-of-pocket costs, mode of administration, time to onset of efficacy, and administration setting. Providers had similar but slightly different priorities, with mode of administration, time to onset of efficacy, dosing frequency, and insurance reimbursement and access.

After initiation, pharmacists must also maintain ongoing follow-up, Autry said. Defining a “success” can be challenging, however, with the various priorities between patients and clinicians. For example, researchers found that allergists consider reduction in exacerbations, improvement in forced expiratory volume in 1 second (FEV1), reduction in oral corticosteroid use, and improved symptoms when defining a “success.”

“Interestingly, response to biomarkers and that change in serum concentrations was a little bit lower on the list,” Autry said.

It is important for pharmacists to set realistic expectations with patients, as well. It can take between 4 and 6 months to see affects after the initial exposure, and in some patients, it could be upwards of 1 year.

Helping patients and caregivers manage prior authorizations and accessibility is also a crucial role for pharmacists. Nelson said that after 5 years of receiving his biologic medication, a change in insurance caused her son to lose access for 2 months. In just that short period, he became sick and was hospitalized, after 5 years without a hospitalization.

“It was incredibly frustrating to see my son go through this when we knew what worked for him…even after the history that we had established [with insurance], it was incredibly frustrating and heartbreaking to see my son in the hospital when we knew what worked,” Nelson said.

During his hospital stay, the pharmacy team helped verify all of his medications and organized anything they needed during the transition back to home. Nelson emphasized that they have been with the same pharmacist for the past 5 years, and her assistance and education is crucial.

“We’ve had a lot of interaction,” Nelson said. “She is a plethora of information…any resource we need, we can ask her, especially as it pertains to our biologic or any of Cade’s inhalants or any of the medications he’s on. We’ve gained a rapport with her and it’s someone I feel we can trust, and she’s definitely an integral part of his team.”

REFERENCE

Anderson WC, Autry E, Nelson J. Utilizing Biologics for the Management of Persistent Moderate to Severe Asthma: Opportunities for the Specialty Pharmacist to Optimize Care. Presented at: 2023 Asembia Summit. May 1, 2023. Accessed May 1, 2023.