ERS 2023 Research Addresses Asthma Clinical Remission and ECOPD Therapies

The definition of clinical remission in asthma was the subject of research presented at the 2023 European Respiratory Society (ERS) International Congress, which took place from September 9 to 13 in Milan, Italy. A number of studies on achieving clinical remission in asthma and reducing exacerbations of COPD were also presented at the conference.

Defining Asthma Clinical Remission

Clinical remission is a goal of asthma management; however, the precise definition of clinical remission is subject to debate. In the real-world REDES study, researchers found that mepolizumab resulted in clinical remission in severe asthma in 37% of the study’s 644 participants, based on a definition of clinical remission with 3 components: no use of corticosteroids, no exacerbations, and an Asthma Control Test (ACT) score of at least 20.

Researchers performed a post hoc analysis of REDES to assess the effect of adding lung function outcomes as a fourth component of the definition of asthma clinical remission. The study endpoint: the number of patients achieving clinical remission at week 52 based on a definition of clinical remission that included a lung function parameter.

The post hoc investigators evaluated lung function in REDES participants using 5 parameters of post-bronchodilator (BD) forced expiratory volume in 1 second (FEV₁): (1) at least 80% of the predicted value; (2) improvement from baseline of at least 100 mL; (3) improvement from baseline of at least 0 mL; (4) a worsening from baseline of 50 mL or less; and (5) a worsening from baseline of 100 mL or less.

The investigators found that in contrast to the 37% of patients achieving clinical remission in REDES using the 3-component definition clinical remission, the percentage of REDES patients achieving clinical remission when a lung function parameter was added was somewhat lower, varying from 22% to 31% depending upon which lung function parameter was used:

• At least 80% of predicted FEV₁ value: 30%
• At least 100 mL improvement from baseline: 22%
• At least 0 mL improvement from baseline: 27%
• 50 mL or less fewer from baseline: 30%
• 100 mL or fewer worsening from baseline: 31%

The investigators said their findings offered insight into the definition of clinical remission. They also noted that “Similar outcomes were observed with the ≥80% predicted FEV₁ and ≤50 mL worsening from baseline in post-BD FEV₁ parameters, which may reflect natural loss of lung function that occurs with age.”

Clinical Remission With Tezepelumab

Another post hoc analysis presented at ERS 2023 assessed clinical remission achieved with tezepelumab treatment for severe, uncontrolled asthma. This analysis found that 2 years of tezepelumab treatment improved clinical remission, which the investigators generally defined as “long-term disease stabilization and control with or without ongoing treatment.” 

Criteria for clinical remission in this analysis were: an Asthma Control Questionnaire-6 (ACQ-6) score less than 1.5; FEV₁ at least 95% of baseline at the end of each year; and no exacerbations requiring the use of oral corticosteroids throughout 104 weeks.

The post hoc exploratory study evaluated rates of on-treatment remission after 2 years of tezepelumab treatment using data from patients who participated in the phase 3 DESTINATION (ClinicalTrials.gov Identifier: NCT03706079) and NAVIGATOR (ClinicalTrials.gov Identifier: NCT03347279) trials. A total of 379 patients who received tezepelumab and 187 patients who received placebo in the NAVIGATOR and DESTINATION extension studies were included in the post hoc analysis of clinical remission analysis.

Approximately 27.2% of patients receiving tezepelumab for 52 to 104 weeks achieved remission, compared with 20.9% of those receiving placebo. The percentage of patients achieving remission with tezepelumab was highest between 25 to 52 weeks (37.2%), whereas the percentage of those achieving remission in the placebo group was highest between 0 to 24 weeks (30.5%).

The study authors concluded that “Among patients with severe, uncontrolled asthma, a numerically greater proportion of patients who received tezepelumab than placebo achieved remission during the time periods assessed.”

Benralizumab Lowers ECOPD Recurrence  

The effect of benralizumab on exacerbations of chronic obstructive pulmonary disease (ECOPD) was addressed in another ERS 2023 presentation, which found that benralizumab 100 mg lowered ECOPD risk and substantially lengthened the time to recurrent moderate or severe ECOPD. These findings may be helpful for addressing the 30-day readmission rate in patients hospitalized for ECOPD, the presenters noted.

The presenters reported on a post-hoc analysis of 145 individuals participating in the GALATHEA (ClinicalTrials.gov Identifier: NCT02138916) and TERRANOVA (ClinicalTrials.gov Identifier: NCT02155660) trials, comparing how benralizumab treatment vs placebo affected the risk for moderate or severe recurrent ECOPD. Patients studied had an eosinophil count of at least 300, were on triple therapy, and had experienced 3 or more ECOPD in the last year; notably, patients included for analysis had experienced at least 1 ECOPD after being randomly assigned to receive benralizumab.

The investigators estimated time to recurrent ECOPD using a Kaplan-Meier curve. The estimated median time to recurrent ECOPD among the 73 patients receiving benralizumab was 150 days (95% CI, 113-225 days) vs 85 days (95% CI, 61-108 days) among the 72 patients receiving placebo. Overall, patients receiving benralizumab took on average 1.76 times longer to experience recurrent ECOPD than patients receiving placebo.

“This analysis suggests that benralizumab 100 mg may reduce the risk of, or prolong time free from, a recurrent ECOPD in this subgroup and supports continued investigation of benralizumab in COPD in the ongoing phase 3 RESOLUTE (NCT04053634) study,” the researchers concluded.

Dupilumab Beneficial for COPD With T2 Inflammation

The effect of dupilumab vs placebo on multiple manifestations of COPD with type 2 (T2) inflammation was also addressed by new research presented at ERS 2023. The researchers found that dupilumab significantly improved moderate to severe exacerbations, pre-bronchodilator FEV₁, and the need for systemic corticosteroids in this patient population.

The researchers reported results from the BOREAS trial (ClinicalTrials.gov Identifier: NCT03930732), a 52-week phase 3, randomized, double-blind, placebo-controlled trial studying the safety and efficacy of biweekly dupilumab 300 mg in patients with moderate to severe COPD and T2 inflammation. This condition was defined by the following criteria: an elevated eosinophil count (≥300 cells/µL); use of triple therapy (inhaled corticosteroid plus long-acting beta-2 agonist plus long-acting muscarinic agonist), and no history or diagnosis of asthma.

The study involved 939 participants; of those, 468 received dupilumab every 2 weeks and 471 received placebo. The primary endpoint was the annualized rate of moderate to severe exacerbations; notable secondary endpoints included the cumulative number of exacerbations over time and change from baseline in pre-bronchodilator FEV₁ at weeks 12 and 52.

The researchers found that:

• Dupilumab lowered exacerbation rates by 30% compared with placebo (P =.0005).
• Use of dupilumab was associated with an increased pre-bronchodilator FEV₁ at week 12 (83 mL; P <.0001), a benefit sustained through week 52 (83 mL; P =.0003).
• Use of dupilumab vs placebo was associated with decreased use of systemic corticosteroids due to COPD exacerbation over the course of the year.

Overall, the researchers concluded that dupilumab “significantly improved moderate-severe exacerbations, lung function, quality of life, and symptoms in COPD patients with T2 inflammation,” and that there was a trend towards fewer days of corticosteroid treatment for acute ECOPD among patients using dupilumab.