Biologics bootcamp: CHEST attendees discuss the latest advances in biologic therapies
Key Takeaways
With six biologics approved, each addressing specific biomarkers, clinicians can tailor treatments to individual patient profiles, significantly improving outcomes for severe asthma patients.
Experts at CHEST recommend biologic choices based on patient-specific factors such as exacerbation history, lung function, and corticosteroid dependency,
This article is part of our CHEST 2024 coverage. Explore more.
Remission could be possible for severe asthma patients being treated with biologics, according to experts at this year’s CHEST conference. With a number of biologics on the market—each addressing different patient biomarkers—clinicians can really zero in on that coveted patient success.
There are six currently approved biologics on the market. They include:
Omalizumab (targets IgE, IgE level (30-70 IU ml) + perennial allergies
Mepolizumab (targets IL-5, eosinophils >150 cells /mL)
Reslizumab (targets IL-5, eosinophils >400 cells /mL)
Benralizumab (targets IL-5R, eosinophils >150 cells /mL)
Dupilumab (targets IL-4R, eosinophils >150 cells /mL of FeNO >25 ppb)
Tezepelumab: Targets thymic stromal lymphopoietin, or TSLP—no biomarker needed.
Biologics guidelines
While there has never been a head-to-head trial to determine which biologic is the most effective for which patient, an assemblage of CHEST cochairs, panelists, methodologists, and guideline development experts came together to create a set of guidelines for treating severe asthma patients with biologics. Their suggestions were founded on evidence and based on expert consensus:
Omalizumab or Dupilumab for patients over the age of 18 with moderate to severe allergic asthma and over one exacerbation requiring oral corticosteroids. Omalizumab or Dupilumab.
Dupilumab over Omalizumab for patients with allergic asthma and frequent (over 2) exacerbations or severe exacerbations requiring hospitalization.
Dupilumab over Omalizumab for patients with allergic asthma and low lung function (<70% predicted).
Anti-IL5/Ra therapy or Dupilumab over Tezepelumab for patients over 18 with steroid-dependent asthma.
Second-line choices: Anti-IL5/Ra or Tezepelumab for patients over 18 with severe asthma who did not respond to Dupilumab. IL5/Ra therapy over Tezepelumab for steroid-dependent patients.
Disclaimer
All of the above suggestions came with a disclaimer: These were conditional recommendations due to low or very low certainty of evidence. Megan Conroy, MEd, MD, FCCP, said that the guideline’s values lie not only in the recommendations themselves but in the very discussion they inspire. “We are optimistic that these guidelines can help you make choices, or feel supported,” Dr. Conroy said.
Biologics in the pipeline
But that’s not all. There are other therapies on the horizon, too. “There are many pipeline therapies in severe asthma that appear promising, including data from phase 3 study of ultra-long acting anti-IL5 ab (Depemokimab) that was recently published in the New England Journal of Medicine,” Sandhya Khurana, MD, FCCP, professor of Pulmonary & Critical Care Medicine at the University of Rochester, NY tells MDLinx.com. Dharani Narendra, MD, FCCP heartily agrees: “Depemokimab will be a game changer, as it is an ultra-long acting biologic requiring only 2 injections in a year.”
Biologics for non-T2 asthma
During the CHEST session Advances in Non-T2 Asthma, experts discussed the hallmarks of non-T2 asthma as well as therapies to treat it. While the majority of current biologics don’t address non-T2 asthma—leaving a definitive gap in the market, a topic many experts addresses during the conference—Tezepelumab may be efficacious in patients with poorly controlled moderate to severe asthma, T2 or not. According to research published in Respirology Case Reports, a patient with non‐eosinophilic asthma had a good clinical response with tezepelumab after being unresponsive to benralizumab, dupilumab, and mepolizumab.
According to Praveen Akuthota, MD, more treatments may be coming down the pipeline, as researchers are looking into both JAK inhibitors and tyrosine kinase inhibitors (for low-T2).
“Non-T2 asthma remains an area of unmet need and more research is needed for effective therapies in this asthma phenotype,” Dr. Khurana says. When it comes to switching biologics for patients, Dr. Narendra says that several CHEST presenters recommended turning to a 2024 article, Advancing Care in Severe Asthma: The Art of Switching Biologics, published in Advances in Respiratory Medicine as a resource. The researchers underscored the importance of a patient-centered approach, biomarker assessment, and an awareness of the ever-evolving nature of asthma treatment.
Voices from the floor
“There are a few things I ask myself when considering biologic therapy for a patient with severe uncontrolled asthma,” Dr. Khurana says. “[First], do I have the correct diagnosis and is the patient adherent with their medium-high dose ICS/LABA therapy? Biologics are highly effective but also very expensive therapies.”
Further, Dr. Khurana considers the patient’s phenotype and endotype. “Are there comorbidities that can guide the selection of the initial biologic? [We need to] carefully consider the patient’s biomarkers (IgE, allergen sensitization profile, eosinophil count, and FeNO) and comorbidities when selecting the initial biologic.” Dr. Khurana then follows up with the patient three to four months after the biologic was started. “I assess clinical response using ACT/ACQ/AIRQ as well as objective measures (exacerbation frequency, lung function),” she says.