Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial

Abstract

Rationale: Bronchial thermoplasty (BT) is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle.

Objectives: To evaluate the effectiveness and safety of BT versus a sham procedure in subjects with severe asthma who remain symptomatic despite treatment with high-dose inhaled corticosteroids and long-acting beta(2)-agonists.

Methods: A total of 288 adult subjects (Intent-to-Treat [ITT]) randomized to BT or sham control underwent three bronchoscopy procedures. Primary outcome was the difference in Asthma Quality of Life Questionnaire (AQLQ) scores from baseline to average of 6, 9, and 12 months (integrated AQLQ). Adverse events and health care use were collected to assess safety. Statistical design and analysis of the primary endpoint was Bayesian. Target posterior probability of superiority (PPS) of BT over sham was 95%, except for the primary endpoint (96.4%).

Measurements and main results: The improvement from baseline in the integrated AQLQ score was superior in the BT group compared with sham (BT, 1.35 +/- 1.10; sham, 1.16 +/- 1.23 [PPS, 96.0% ITT and 97.9% per protocol]). Seventy-nine percent of BT and 64% of sham subjects achieved changes in AQLQ of 0.5 or greater (PPS, 99.6%). Six percent more BT subjects were hospitalized in the treatment period (up to 6 wk after BT). In the posttreatment period (6-52 wk after BT), the BT group experienced fewer severe exacerbations, emergency department (ED) visits, and days missed from work/school compared with the sham group (PPS, 95.5, 99.9, and 99.3%, respectively).

Conclusions: BT in subjects with severe asthma improves asthma-specific quality of life with a reduction in severe exacerbations and healthcare use in the posttreatment period. Clinical trial registered with www.clinialtrials.gov (NCT00231114).

Figure 1.

Disposition of AIR2 subjects. Of the 288 subjects who underwent a bronchoscopy procedure, 190 were randomized to the bronchial thermoplasty (BT) group, and 98 were randomized to the sham control group. All 288 subjects qualified for the intent-to-treat and safety populations. Additionally, 268 subjects (173 in the BT group and 95 in the sham control group) qualified for inclusion in the per protocol population.

Figure 2.

Change in asthma quality of life by treatment group. (A) Change in Asthma Quality of Life Questionnaire (AQLQ) score over 12 months after treatment with bronchial thermoplasty (BT) (diamonds) or sham control (squares) in the per protocol population. *Posterior probability of superiority = 97.9%. (B) Percentage of subjects achieving an AQLQ score change of 0.5 or greater (the minimal important difference), −0.05 to less than 0.5, and −0.5 after treatment with BT (blue) or sham control (gray) in the per protocol population. **Posterior probability of superiority = 100.0% for “Net” benefit ([proportion improving–proportion deteriorating in the BT group] – [proportion improving–proportion deteriorating in the sham group]).

Figure 3.

Healthcare utilization events during the posttreatment period. Severe exacerbations (exacerbation requiring treatment with systemic corticosteroids or doubling of the inhaled corticosteroids dose), emergency department visits, and hospitalizations occurring in the posttreatment period. Open bars, sham; shaded bars, bronchial thermoplasty. All values are means ± SEM. *Posterior probability of superiority = 95.5%. ^†Posterior probability of superiority = 99.9%.