Comments on “Established and Emerging Biological Therapies for the Treatment of Comorbid Asthma and Chronic Obstructive Pulmonary Disease” [Letter]

Dear editor

We read with interest the article by Cazzola et al recently published in the Journal of Inflammation Research titled “Established and Emerging Biological Therapies for the Treatment of Comorbid Asthma and Chronic Obstructive Pulmonary Disease”¹ We would like to clarify two points made regarding the evaluation of the anti-thymic stromal lymphopoietin (TSLP) antibody, tezepelumab, in patients with asthma-chronic obstructive pulmonary disease overlap (ACO) and in patients with chronic obstructive pulmonary disease (COPD).

In the authors’ review of relevant data describing the effects of tezepelumab in patients with ACO, it was stated that tezepelumab has not been formally evaluated in clinical trials targeting ACO.¹ We would like to note that the Phase 4 PASSAGE study (ClinicalTrials.gov identifier: NCT05329194), which prospectively assessed the effectiveness and safety of tezepelumab in a real-world population of patients with severe uncontrolled asthma, included the pre-specified enrollment of patients with a diagnosis of comorbid mild-to-moderate COPD.^2,3 Diagnosis of comorbid mild-to-moderate COPD consistent with the 2024 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines⁴ was confirmed before enrollment by investigators. A pre-specified interim analysis of PASSAGE presented early findings in this population² and the final results were published recently.³ This ACO subgroup (n = 57), 70% of whom had a baseline blood eosinophil count (BEC) of <300 cells/µL, experienced a relative reduction in the annualized asthma exacerbation rate of 65% (95% confidence interval [CI]: 46, 78) following tezepelumab initiation. This reduction was consistent with exacerbation reductions observed in other PASSAGE study subgroups (54–82%). Furthermore, an 80 mL (95% CI: –50, 210) improvement in pre-bronchodilator forced expiratory volume in one second (pre-BD FEV₁) from baseline to week 52 was observed in the ACO subgroup, which increased to 170 mL (95% CI: 0, 330) among those with ACO and a percent predicted pre-BD FEV₁ ≤ 80% at baseline.

Additionally, in their discussion of the Phase 2a COURSE study, which assessed the efficacy of tezepelumab in patients with moderate to very severe COPD (ClinicalTrials.gov identifier: NCT04039113), the authors stated that subgroup analyses across baseline BEC strata did not identify a patient population with a consistent response.¹ However, as described by Singh et al (in the supplementary appendix), there were consistent improvements across multiple endpoints with tezepelumab compared with placebo in patients with a baseline BEC ≥150 cells/µL. In this subgroup, there was a 37% reduction in moderate or severe COPD exacerbations over 52 weeks (95% CI: 7, 57; nominal 1-sided p = 0.011; negative binomial model), a 63 mL increase in pre-BD FEV₁ at week 52 (95% CI: 9, 116; nominal p = 0.023; mixed model for repeated measures), and a 4.23-point reduction (ie, improvement) in St George’s Respiratory Questionnaire total score at week 52 (95% CI: −8.51, 0.06; nominal p = 0.053; mixed model for repeated measures).⁵ Subpopulation treatment effect pattern plots assessing tezepelumab efficacy over the baseline BEC continuum also showed a greater magnitude of effect with greater BEC, with a clear inflection point at a BEC of 150 cells/μL for exacerbation reduction.⁵

Taken together, these data indicate potential benefits of tezepelumab in patients with eosinophilic COPD (baseline BEC ≥150 cells/µL) or severe asthma with comorbid COPD regardless of baseline BEC.

Funding Statement

This communication was funded by AstraZeneca and Amgen Inc.

Data Sharing Statement

No new data were generated for this communication.

Author Contributions

CSA: writing – original draft; writing – review and editing. BE: writing – review and editing. NLL: writing – review and editing. All authors gave final approval of the version to be published; have agreed on the journal to which the communication has been submitted; and agreed to be accountable for all aspects of the work.

Disclosure

Dr. Christopher Ambrose: Employee of AstraZeneca and may own stock or stock options in AstraZeneca. Reports other relationships with AstraZeneca, outside the submitted work.

Dr. Benjamin Emmanuel: Employee of AstraZeneca and may own stock or stock options in AstraZeneca. Reports other relationships with AstraZeneca, outside the submitted work.

Professor Njira Lugogo: Has received consultancy fees for participation in advisory boards from AbbVie, Amgen, Apogee, AstraZeneca, Foresee, Genentech, GSK, Incyte, Novartis, Regeneron Pharmaceuticals, Sanofi, and Teva Pharmaceuticals; has received fees for non-speaker bureau presentations from AstraZeneca and GSK; has received speaker fees (own content) from NIOX; has received travel support from AstraZeneca; and her institution has received research support from Amgen, AstraZeneca, Avillion, Genentech, Gossamer Bio, GSK, Janssen, Novartis, Regeneron Pharmaceuticals, Roche, Sanofi, and Teva Pharmaceuticals during the conduct of the study.