Type 2 (T2)-targeted biologics have utility in the management of T2-low asthma, but more effective therapies are needed: Implications of EMBER study

The real-world study, “Response to biologics along a gradient of T2 involvement in patients with severe asthma: a data-driven biomarker clustering approach”, was recently published in The Journal of Allergy and Clinical Immunology: In Practice. Five biomarker clusters along a gradient of T2 involvement were identified using a data-driven approach instead of the pre-defined thresholds used in prior studies. Biologic use (Anti-IgE, Anti-IL5/5R and Anti-IL4Rα) was associated with improved outcomes in all clusters but tended to be better at the higher end of the T2 spectrum. Interestingly, we demonstrated that T2-targeted biologics have utility in the management of triple-biomarker-low asthma. Further research is needed to identify pathways specific to T2-low asthma that can be targeted by treatment.

The EMBER study included data from 3,675 patients across 23 countries in the International Severe Asthma Registry (ISAR). Of these patients, 16.4% were in Cluster A (T2-low, triple-biomarker-low), 20.4% were in Cluster B (high immunoglobulin E [IgE], intermediate blood eosinophil count [BEC]), 22.9% were in Cluster C (high BEC and fractional exhaled nitric oxide [FeNO]), 30.3% were in Cluster D (triple-biomarker-intermediate) and 10.0% were in Cluster E (triple-biomarker-high) (Figure 1).

Figure 1. Biomarker clusters of patients with severe asthma, identified using Gaussian finite mixture models. Abbreviations: BEC = blood eosinophil count; FeNO = fractional exhaled nitric oxide; IgE = immunoglobulin E; T2: Type 2

In multivariable analysis, biologic use was associated with improved outcomes in all clusters but tended to be better at the higher end of the T2 spectrum. For example, patients in cluster C had a significantly greater pre- to post-biologic increase in forced expiratory volume in 1 second (FEV₁) relative to cluster A (0.16 vs. 0.04L) (Figure 2). Although we observed clinical improvements across all clusters and biologic classes (Anti-IgE, Anti-IL5/5R and Anti-IL4Rα), among those treated with Anti-IL5/5R there was some evidence of more modest improvements for patients with triple-biomarker-low asthma. Anti-TSLP, a newer biologic therapy, was not included in the EMBER study. In other studies, patients with severe, uncontrolled asthma who were treated with Anti-TSLP experienced reductions in exacerbations versus placebo, independent of BEC, FeNO, or T2 status, but it was more effective in those with increased BEC and FeNO levels.^1-3

Figure 2. Change in FEV₁ pre- to post-biologic relative to Cluster A (T2-low). The data are presented as relative risk (RR) with 95% confidence intervals adjusted for pre-biologic outcome, age, sex, country, and pre-biologic long-term oral corticosteroid.

The EMBER study has identified biomarker clusters along a gradient of T2 involvement in a large, international severe asthma population and showed that biologic use was associated with improved outcomes across all clusters and biologic classes. While the study findings indicate that T2-targeted biologics have utility in the management of T2-low asthma, more effective therapies are needed for these patients.

To learn more about the EMBER study, please read the full publication in The Journal of Allergy and Clinical Immunology: In Practice, as well as the accompanying slide deck. The EMBER study was conducted by the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was co-funded by Optimum Patient Care Global (OPCG) and AstraZeneca Ltd. ISAR is operated by OPCG and co-funded by OPCG and AstraZeneca.

About OPRI

The Observational and Pragmatic Research Institute (OPRI) is an internationally recognized independent research organization dedicated to providing real-world evidence that supports best practices in chronic disease management in primary care. Learn more at https://www.opri.org.uk/. For media inquiries and additional information, please contact https://www.opri.org.uk/contact.

About ISAR

The International Severe Asthma Registry (ISAR) is the first global adult severe asthma registry, providing a rich, standardized dataset to advance research, clinical practice, and policy in severe asthma care. Since its establishment in 2017, ISAR has recruited >35,000 patients from 29 countries, and achieved 36 publications. ISAR fosters international collaboration to improve outcomes for patients worldwide. Learn more at https://www.isar.opcglobal.org.

References

1. Menzies-Gow AN, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med 2021; 384: 1800–9.

2. Corren J, Menzies-Gow AN, Chupp G, Israel E, Korn S, Cook B, et al. Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials. Am J Respir Crit Care Med 2023; 208: 13–24.

3. Corren J, Parnes JR, Wang L, Mo M, Roseti SL, Griffiths JM, et al. Tezepelumab in Adults with Uncontrolled Asthma. N Engl J Med 2017; 377: 936–46.