Trial Shows Positive Long-term Safety Profile for Denervation Therapy in COPD

Results from the AIRFLOW-1 trial assessing the long-term effects of targeted lung denervation (TLD) in patients with chronic obstructive pulmonary disease (COPD) show that the therapy had a positive safety profile up to 3 years.

The study, published in Respiratory Research, demonstrates that use of TLD did not result in late-onset serious adverse events (AEs) related to denervation therapy. Lung function, quality of life, and exacerbation rates were stable through the 3-year follow-up.

Patients with COPD receiving inhaled medications often continue to have exacerbations. Acute changes in lung physiology from infections and inflammation can reduce medications’ benefits. Only about 50% of patients experience clinically significant benefits from a long-acting muscarinic antagonist, and up to 70% continue to have exacerbations while on optimal medical therapy.

TLD is a bronchoscopic therapy delivered through a dual-cooled radiofrequency catheter that interrupts parasympathetic pulmonary nerve input to the lung to reduce the adverse impacts of cholinergic hyperactivity responsible for worsened COPD symptoms, including inflammation.

Previous research has demonstrated the safety of TLD, but long-term effects of the procedure have only been assessed for an older generation of the device.

AIRFLOW-1 was a randomized, double blind, multicenter study assessing TLD in 46 patients with moderate to severe symptomatic COPD. Patients were randomized to receive TLD at either 29 W or 32 W power, with 15 patients assigned to each group. Additionally, an open-label group of 16 patients treated with 32 W power was used to confirm safety improvements afterprocedural enhancements following gastrointestinal AEs.

Patients were followed-up at 1, 2, and 3 years after receiving TLD, and data were available for 80.4% of patients at 2 years and 73.9% at 3 years.

At the 2- and 3-year follow-ups, no serious gastrointestinal AEs were observed that were determined to be caused by the procedure or device. One patient experienced a severe gastric AE 650 days after the procedure; however, this was determined to be caused by increased dysphagia, which fully resolved and was considered unrelated to the therapy.

There was 1 death in the confirmation group attributed to an acute cardiac event 1128 days after receiving TLD, but it also was not determined to be related to the therapy.

Annual rates of moderate or severe COPD exacerbations were stable for the 3 years, with 70% of patients experiencing at least 1 moderate to severe exacerbation at year 1, 61% of patients at year 2, and 46% at year 3.

Pulmonary function at 1 year post procedure improved by an average of 60 mL (P = .031) in forced expiratory volume and 219 mL (P = .004) in forced vital capacity. However, the investigators did not observe any significant differences in baseline measurements at the 2- and 3-year follow-ups.

A similar effect occurred in COPD Assessment Test scores evaluating quality of life, where an average decrease of 3.03 points was seen at the 1-year follow-up. Again, no significant differences were observed at the 2- or 3-year follow-up.

The investigators noted that the small cohort size and lack of a control group were the main limitations of the study.

“These observations will need to be confirmed in an ongoing large-scale sham-controlled randomized trial (AIRFLOW-3) comparing the efficacy of TLD plus optimal medical care for patients with moderate to severe COPD against optimal medical care for COPD,” the investigators wrote.

The AIRFLOW-3 trial is currently recruiting and is expected to finish in April 2027.

Reference

Christophe P, Pallav LS, Dirk-Jan S, et al. Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes. Published online February 19, 2021. doi:10.1186/s12931-021-01664-5