Biologics Treatment Response Patterns Comparable in Patients With ACO, Asthma


The efficacy of biologics suggests a potential for biologic-based treatment for patients with asthma-chronic obstructive pulmonary disease overlap.

Key Takeaways

  1. Biologic Treatment in ACO and Pure Asthma: The study investigates the use of biologics in patients with asthma-chronic obstructive pulmonary disease overlap (ACO) compared to those with pure asthma. Biologics, including omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab, were assessed for their impact on clinical outcomes such as inflammatory markers, lung function, symptom control, and exacerbation rates.
  2. Positive Treatment Responses in ACO and Asthma Groups: Both ACO and pure asthma groups exhibited positive responses to biologic treatment, including improvements in forced expiratory volume in 1s, asthma control test scores, reductions in inhaled corticosteroid/oral corticosteroid doses, fractional exhaled nitric oxide levels, blood and sputum eosinophil counts, and exacerbation frequency. ACO patients, however, showed lower blood eosinophil counts, less atopy, and lower lung function compared to pure asthma patients.
  3. Biologic-Specific Differences and Considerations: Differences were observed in the use of specific biologics between the ACO and pure asthma groups. Dupilumab was more frequently used in the ACO group, whereas omalizumab and benralizumab were not used in the ACO group at all. In addition, specific variations were noted in treatment responses depending on the biologic used, emphasizing the need for personalized approaches in ACO management. The study authors note that longer-term studies with a larger patient population are suggested to fully understand the efficacy of biologics in ACO treatment.

Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a heterogeneous condition that shares characteristics of both COPD and asthma, both of which are chronic inflammatory airway diseases; however, ACO has shown to have worse clinical outcomes and higher mortality rates. There is currently no effective or specific treatment for ACO, and its pathophysiology remains unclear.

A study published in World Allergy Organization Journal examined the use of biologics in patients with ACO by comparing clinical outcomes, such as inflammatory markers, lung function, symptom control, and exacerbation rates, between patients with asthma and ACO. The prospective, observational, multicenter cohort study enrolled 94 patients with severe asthma who were attending asthma clinics in both Korea and the United Kingdom. The enrolled patients were between the ages of 18 and 80 years and were classified as having severe asthma, according to guidelines from the European Respiratory Society/American Thoracic Society. Of the 94 participants enrolled in the study, 13 had ACO and 81 had pure asthma.

ACO was defined as asthma with post-bronchodilator (BD) airway flow limitation measured by forced expiratory volume in 1s/forced vital capacity (FEV1/FVC <0.7) and smoking history of 10 pack-years or more. Additionally, based on results from skin prick tests, blood eosinophils, sputum eosinophils, fractional exhaled nitric oxide (FeNO) levels, patients were classified into type 2 (T2)-high or T2-low asthma. T2-high asthma was defined as meeting 1 or more of the following criteria: blood eosinophils greater than or equal to 150 per μL, sputum eosinophils greater than or equal to 2%, FeNO levels greater than or equal to 20 ppb, and suspected allergic asthma with sensitivity to inhalant allergen. The patients with T-2 high asthma were newly treated with biologics­—such as omalizumab (Xolair; Genentech USA, Novartis Pharmaceuticals), mepolizumab (Nucala; GlaxoSmithKline), reslizumab (Cinqair; Teva Support Solutions), benralizumab (Fasenra; AstraZeneca), and dupliumab (Dupixent; Regeneron, Sanofi)—or continued receiving treatment according to clinical protocols with follow-up evaluations being performed at baseline, 1 month, 6 months, and 12 months.

The study results demonstrated that both the ACO and pure asthma groups showed positive treatment responses to biologics, including improvements in FEV1 and asthma control tests (ACT) scores, reductions in inhaled corticosteroid (ICS)/oral corticosteroids (OCS) doses, FeNO levels, blood and sputum eosinophil counts, and exacerbation frequency; however, patients in the ACO group exhibited lower blood eosinophil counts (453.3 ± 304.5 vs 730.9 ± 588.3/μL, P = 0.015), less atopy (18.2% vs 65.5%, P = 0.007, lower post-BD FEV1 (47.8 ± 18.8 vs. 67.6 ± 19.0%, P = 0.001), and FEV1/FVC ratio (0.50 ± 0.13 vs 0.68 ± 0.12, P < 0.001) compared to patients with pure asthma. Among the biologics used, dupliumab was more frequently used in the ACO group than the pure asthma group (61.5% vs 23.5%), whereas omalizumab and benralizumab were not used in the ACO group at all.

In addition, patients with ACO who were treated with reslizumab had a lower post-BD FEV1/FVC ratio (0.53 ± 0.12 vs 0.70 ± 0.10, P = 0.038) and a higher smoking pack-year (32.3 ± 15.7 vs 10.0 ± 10.6, P = 0.042) compared to patients in the pure asthma group who were treated with reslizumab, and patients with ACO treated with dupilumab had lower pre-BD FEV1/FVC ratio (0.50 ± 0.17 vs 0.65 ± 0.14, P = 0.037), post-BD FEV1/FVC ratio (0.47 ± 0.15 vs 0.68 ± 0.13, P = 0.012), and a higher smoking pack-year (31.1 ± 18.3 vs 14.9 ± 17.8, P = 0.019) than those with pure asthma who received dupilumab. Further, there were no significant differences in blood and sputum eosinophils, serum IgE, comorbidities, or other factors between the 2 groups.

Young woman using blue asthma inhaler

Image credit: Orawan |

Additionally, both the ACO and asthma groups demonstrated positive responses with no significant differences in FEV1 improvement (10.7 ± 17.2 vs 11.3 ± 12.9 %, P = 0.652), ACT score increase (3.3 ± 5.5 vs 5.4 ± 5.4, P = 0.290), reduction in ICS dose (−66.7 ± 460.0 vs −17.9 ± 236.2 mcg/day, P = 0.912), reduction in OCS maintenance dose (−117.5 ± 94.4 vs −115.1 ± 456.9 mg, P = 0.688), reduction in FeNO levels (−18.6 ± 24.7 vs. −14.7 ± 45.4 ppb, P = 0.415), reduction in sputum eosinophils (−3.4 ± 10.6 vs −14.5 ± 24.0 %, P = 0.065), and decrease in exacerbation frequency (−0.96 ± 2.47 vs −1.40 ± 2.63, P = 0.575); however, the most significant difference observed was a decrease in blood eosinophil levels (−36.5 ± 517.0 vs −363.2 ± 1294.6/μL, P = 0.013). There were also no significant differences when comparing the ACO and asthma groups for each biologic.

Study limitations include the small sample size, the short follow-up period of 6 to 9 months, and the exclusion of omalizumab and benralizumab in the ACO group. In addition, the authors note that more reliable results could have been gathered if more ACOs using biologics had been included. The authors emphasize that although biologics show comparable efficacy in the treatment of patients with ACO than patients with pure asthma, further research with longer treatment durations and extended follow-up periods are necessary to determine the full effect biologics can have when treating ACO and pure asthma.


Shim J, Kim H, Kwon J, et al. A comparison of treatment response to biologics in asthma-COPD overlap and pure asthma: Findings from the PRISM study. World Allergy Organization Journal. 2023;16(12):100848. doi:10.1016/j.waojou.2023.100848

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