Biologics can be excellent supplements to treatment when severe asthma is not fully controlled by high-dose inhaled steroids and long-acting beta agonists. But to prescribe these injectables, doctors must understand which will work best for each patient and how long treatment should last.
The CHEST 2022 case-based discussion, Evolving Paradigms of Treatment Selection in Severe Asthma, on Sunday, October 16, offered guidance on long-term use of standard and novel biologics, formulations that can ease both asthma and related comorbidities, and the challenges of treatment selection.
Studies support long-term use
Dharani Narendra, MD, FCCP, assistant professor at Baylor College of Medicine, reviewed extension studies supporting the long-term use of monoclonal antibodies to lower rates of asthma exacerbation, improve lung function, and reduce reliance on glucocorticoids.
“Biologics have revolutionized the treatment of severe eosinophilic asthma and keeps our patients away from hospitals,” Dr. Narendra said. “We also see that in real-world studies, these biologics are very safe and effective.”
Omalizumab has the longest track record, having demonstrated reduced asthma exacerbations for up to 9 years and heightened asthma control for up to 5 years, she said. Despite some serious cardiovascular adverse events, the drug is considered safe.
Mepolizumab, deemed safe although it can spark respiratory infection, boasts positive data stretching to 4.5 years, as does benralizumab, which has demonstrated a rapid depletion of eosinophils without an increased risk of serious infection and “a significant number of zero exacerbations per year,” Dr. Narendra said. Meanwhile, 2 years of positive findings support both reslizumab and dupilumab.
Although patients are often eager to stop taking biologics, panelists cited increased exacerbations and worsened asthma control with cessation of mepolizumab and recurrent congestion when dupilumab was stopped in patients with nasal polyps.
Alarmin blockers are emerging
Some newer biologics work by blocking alarmins—including tezepelumab, approved by the United States Food and Drug Administration in 2021.
While tezepelumab blocks the activity of thymic stromal lymphopoietin (TSLP), experimental anti-alarmins block other cytokines produced by the airway epithelium in response to allergic or nonallergic stimuli, explained Linda Rogers, MD, FCCP, clinical director of the adult asthma program at Mount Sinai–National Jewish Health Respiratory Institute and associate professor at the Icahn School of Medicine at Mount Sinai.
In a study, tezepelumab reduced asthma exacerbations and disease biomarkers, Dr. Rogers said. And while patients with pronounced type 2 asthma had the best responses, the drug was effective for others, regardless of whether their asthma was associated with allergies, she said.
A promising investigational alarmin blocker is itepekimab, an IL-33 inhibitor that reduced eosinophils, exhaled nitric oxide, and immunoglobulin E in a recent study, Dr. Rogers said. In another study, she said, the ST2 receptor blocker astegolimab reduced exacerbations with an acceptable side effect profile.
Indications are multiplying
Some biologics are particularly suited to specific patients because they treat not only asthma but accompanying comorbidities.
Diego J. Maselli, MD, FCCP, associate professor of medicine at the University of Texas Health Science Center at San Antonio and director of the severe asthma program at University Health System, said omalizumab is approved to treat chronic urticaria and nasal polyps; mepolizumab to treat eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, and nasal polyps; and dupilumab to treat atopic dermatitis, nasal polyps, eosinophilic esophagitis, and prurigo nodularis.
The new indications increase the importance of multidisciplinary discussion when prescribing biologics, Dr. Maselli said.
“It’s important that we talk amongst ourselves, particularly with the ENT and allergy specialists with whom we’ve always collaborated,” he said, “because that will help us select the best therapy for our patients.”
Biologic selection remains a difficult task
With the advantages of biologics comes a challenge: choosing among the many options despite a lack of comparative studies, said Sandhya Khurana, MD, FCCP, professor of medicine and director of the Mary Parkes Center for Asthma at the University of Rochester School of Medicine.
She recommends that doctors consult “A Difficult-to-Treat and Severe Asthma Guide,” updated yearly by the Global Initiative for Asthma, for help choosing among anti-IgE, anti-IL-5/IL-5R, anti-IL-4R, and anti-TSLP biologics by considering type 2 status, predictors of response, comorbidities, payer eligibility criteria, cost, dosing, route, and patient preference. She also praised a decision-making framework featured in a recently published review.
In her own practice, Dr. Khurana prescribes:
- IL-5s for highly eosinophilic disease;
- omalizumab for allergic exacerbations or when pregnancy is planned—along with dupilumab and tezepelumab, omalizumab can also be an option for patients with high FeNO scores;
- tezepelumab in the absence of type 2 biomarkers; and
- mepolizumab, benralizumab, or dupilumab for patients dependent on corticosteroids, with dupilumab preferred if eosinophilia can’t be documented.
Dr. Khurana also factors in comorbidities, the anaphylaxis warning carried by omalizumab and reslizumab, and the fact that only reslizumab and tezepelumab can be self-administered by patients.
She recommends assessing outcomes after 4 months and switching to another biologic if response has not occurred.
In a study, “one in four of our patients did not respond to our first choice of biologic, and when we switched them to a second biologic, they had an incremental benefit from switching, regardless of the biologic they were switched to,” she said.
This session was supported by an educational grant from Genentech, a member of the Roche Group, in collaboration with CHEST’s Airways Disorders Network.