New CHEST Recommendations Guide Biologic Use for Severe Asthma

The American College of Chest Physicians (CHEST) has released a new clinical guideline on biologic management in severe asthma, including 7 evidence-based recommendations for pulmonologists, allergists, and immunologists to inform treatment decision making, many of which favor dupilumab for treatment.1

“Severe asthma affects 5% to 10% of asthma patients but constitutes close to one-half of the medical costs related to asthma due to higher morbidity and health care utilization. Biologic agents have become a standard of care in those unresponsive to standard treatments, yet the choice of biologic agent is complex due to the varying mechanisms of action, efficacies, and lack of head-to-head comparisons. Therefore, clinicians need further clinical guidance to optimize their use,” lead author on the guideline, Amber J. Oberle, MD, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Duke University, Durham, North Carolina, and colleagues wrote.1

Oberle and colleagues conducted a systematic literature review of randomized controlled trials (RCTs) and systematic reviews published in English in the MEDLINE, EMBASE, CINAHL, Web of Science, and CENTRAL databases through August 2024 to address 7 questions developed by an ACCP expert panel of 12 pulmonologists and allergists from 3 countries and created recommendations using The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to assess the certainty of evidence and grading of the clinical recommendations.

“While there are studies available to help guide the clinician for initial biologic selection, to date, there is no published guideline to assist in biologic selection when a patient has tried and failed one or more biologics,” Amber J. Oberle, MD, lead author on the guideline, said in a statement.2 “In addition to following this guideline, decisions as to how to individualize biological therapy should occur under a shared decision-making process that carefully considers underlying asthma comorbidities, T2 biomarkers, injection frequency, mode of administration, and access to resources.”

The questions and recommendations are:

1. Should adults with moderate to severe allergic asthma and a history of at least 1 exacerbation annually requiring oral corticosteroids (OCS) use dupilumab or omalizumab?
   1. In adult patients with moderate to severe allergic asthma and a history of ≥ one exacerbation per year requiring oral corticosteroids, the panel conditionally recommends (very low certainty of evidence) either omalizumab or dupilumab; however, for patients with more frequent or severe exacerbations requiring hospitalization, the panel recommends dupilumab over omalizumab.
2. Should adults with steroid dependent asthma use anti-IL5/5Rα or dupilumab?
   1. For adults with severe, steroid-dependent asthma, the panel conditionally recommends (very low certainty of evidence) anti–IL-5/5Rα therapy or dupilumab, with anti–IL-5/5Rα favored in patients with very high pre-OCS eosinophil counts. Dupilumab should be considered when comorbid atopic dermatitis or eosinophilic esophagitis are present, or either dupilumab or mepolizumab if CRSwNP is present.
3. Should adults with steroid dependent asthma use dupilumab or tezepelumab?
   1. In OCS-dependent severe asthma, dupilumab is conditionally recommended over tezepelumab due to its demonstrated ability to reduce OCS dosing, despite both agents improving key asthma outcomes and lacking direct comparative trials.
4. Should adults with moderate to severe asthma not showing clinical response to omalizumab after 4 to 6 months switch to anti-IL5/5Rα therapy or dupilumab?
   1. For adults with moderate to severe asthma who fail to respond to omalizumab after 4–6 months, the guideline suggests switching to anti–IL-5/5Rα therapy or dupilumab, with agent selection guided by biomarkers such as FENO, eosinophil counts, and comorbidities.
5. Should adults with severe asthma not showing clinical response to anti-IL5/5Rα therapy after 4 to 6 months switch to dupilumab or tezepelumab?
   1. Among patients with severe asthma who do not respond to anti–IL-5/5Rα therapy, the panel conditionally recommends dupilumab or tezepelumab, favoring dupilumab in those who are OCS dependent or have OCS-related complications.
6. Should adults with severe asthma not showing clinical response to dupilumab after 4 to 6 months switch to anti-IL5/5Rα therapy or tezepelumab?
   1. For adults with severe asthma who fail dupilumab after 4–6 months, anti–IL-5/5Rα therapy or tezepelumab is conditionally recommended, with anti–IL-5/5Rα favored in steroid-dependent patients and tezepelumab considered in those with low eosinophils or low FENO.
7. Should fractional exhaled nitric oxide (FENO) levels guide therapy changes to dupilumab in adults with severe asthma on anti-IL5/5Rα therapy not showing clinical response by 4 to 6 months?
   1. The guideline suggests using a post-treatment FENO ≥25 ppb to help guide a switch to dupilumab in patients who fail anti–IL-5/5Rα therapy, while emphasizing that FENO should be interpreted alongside clinical factors and alternative options such as tezepelumab.

“Given that there are currently no comparative effectiveness studies, nor is there a validated, commonly agreed definition of clinical response, biologic therapies can only be individualized in daily practice using indirect comparisons of data (delineated into conditional recommendations),” Oberle and colleagues wrote in the guideline.1 “Decisions as to how to individualize biologic therapy should occur under a shared decision-making process that carefully considers underlying asthma comorbidities, T2 biomarkers, injection frequency, mode of administration, and access to resources.”

References

1. Oberle AJ, Abbas F, Adrish M, et al. Biologic Management in Severe Asthma for Adults: An American College of Chest Physicians Clinical Practice Guideline. CHEST. Published online September 24, 2025. doi: 10.1016/j.chest.2025.08.042

2. CHEST releases guideline on biologic management in severe asthma. EurekAlert! Published January 13, 2026. Accessed January 20, 2026. https://www.eurekalert.org/news-releases/1112522