Alair bronchial thermoplasty system for adults with severe difficult to control asthma

Study component

Description

Objectives/hypotheses

To determine the efficacy and safety of BT in adults with bronchial asthma.

Study design

Systematic review and meta‑analysis.

Inclusion/exclusion criteria

RCTs that compared BT versus any active control in adults with moderate or severe persistent asthma were included.

Primary outcomes

Quality of life (AQLQ), asthma control (ACQ), asthma exacerbations and adverse events.

Statistical methods

Meta‑analyses using a random‑effects model using the inverse variance method.

Participants

3 RCTs (429 participants) with differences in design (2 RCTs compared BT vs. medical management and the other vs. a sham intervention) and participant characteristics (1 RCT included only participants with severe difficult to control asthma; the other 2 included patients with less severe asthma).

Results: Quality of life (AQLQ final scores) at 12 months

WMD score +0.28 points, 95% CI 0.07 to 0.50; p<0.01 but not clinically significant.

Results: Symptom control (ACQ scores)

WMD ‑0.15, 95% CI ‑0.40 to 0.10; p= 0.23.

Results: Exacerbations at 12 months (data not pooled)

AIR trial (Cox et al. 2007): Mild exacerbations during a 2‑week period in which LABA was withdrawn: BT: ‑0.16 ± 0.37 vs. control: 0.04 ± 0.29, p<0.05. Severe exacerbations: BT: 0.01 ± 0.08 vs. control: 0.06 ± 0.24, NS.

AIR2 trial (Castro et al. 2010): Patients with severe exacerbations: BT 50/190 (26.3%) vs. control: 39/98 (39.8%). Rate of severe exacerbations per patient per year: 0.48 ± 0.067 vs. 0.70 ± 0.122, p<0.05.

Results: Hospitalised for an adverse event during treatment period

BT: 24/260,^a control: 4/169;^a RR 3.50 (95% CI 1.26 to 9.68), p=0.016.

Results: Hospitalised for an adverse event during post‑treatment period

BT: 11/260;^a control: 7/169;^a RR 1.12 (95% CI 0.44 to 2.85), p=0.82.

Results: Visits to the emergency department during post‑treatment period (data from 1 trial only)

AIR2 trial (Castro et al. 2010): BT: 0.07 visits/year (8.4% of patients), sham treatment: 0.43 visits/year (15.3% of patients).

Results: Use of rescue medication at 12 months of follow‑up (short‑acting bronchodilator puffs per week)

WMD: ‑0.68 (95% CI ‑3.63 to +2.28), p=0.65.

Results: Hospitalised for an adverse event during 5 year follow‑up period (data from 1 trial only)

(Pavord et al. 2007): overall rate of 0.23 hospitalisations per patient per year during 5 years following BT compared with 0.71 hospitalisations per patient per year before BT (BT patients only).

Results: Severe exacerbations during 5 year follow‑up period (data from 1 trial only)

AIR2 trial (Castro et al. 2010): 30.9% of BT patients in the year after BT (and maintained during the 5 year follow‑up) compared with 51.6% of BT patients in the 12 months before BT.

Conclusions

BT for patients with moderate to severe asthma provides a modest clinical benefit in quality of life and lower rates of asthma exacerbation, but no significant difference in asthma control scores. The quality of life findings are at risk of bias, as the main benefits were seen in the 2 studies that did not include a sham treatment arm. BT increases the risk of adverse events during treatment but has a reasonable safety profile after completion of the bronchoscopies. The overall quality of evidence is moderate. Patient data should be collected by independent clinical registries.

Abbreviations: ACQ, Asthma Control Questionnaire; AQLQ, Asthma Quality of Life Questionnaire; BT, bronchial thermoplasty; CI, confidence interval; LABA, long‑acting β2‑adrenergic agonists; NS, not statistically significant; RCT, randomised controlled trial; RR, relative risk; WMD, weighted mean difference.

^aDenominator is all randomised patients.

Study component

Description

Objectives/hypotheses

To evaluate the efficacy and safety of BT in the treatment of patients with moderate to severe persistent asthma.

Study design

Systematic review and meta‑analysis.

Inclusion/exclusion criteria

RCTs that compared BT versus any active control in adults with moderate or severe persistent asthma were included.

Primary outcomes

AQLQ scores.

Statistical methods

ITT analysis; heterogeneity assessed; when hypothesis of homogeneity was not rejected, a fixed‑effects model used; otherwise random effects model used.

Participants

3 RCTs (421 participants) with differences in design (2 RCTs compared BT vs. medical management and the other vs. a sham intervention) and participant characteristics (1 RCT included only participants with severe difficult to control asthma; the other 2 included patients with less severe asthma).

Results: Quality of life (AQLQ change scores) at 12 months

BT vs. maintenance medication (2 trials): WMD 0.86 (95% CI 0.47 to 1.25); p<0.01.

BT vs. sham BT treatment (1 trial): BT: 1.35 ± 1.10; sham: 1.16 ± 1.23 (posterior probability of superiority, 96.0%).

Results: Mean improvements in morning PEF at 12 months

BT vs. either comparator (3 trials): WMD 21.78 l/min; 95% CI 8.06 to 35.50, p = 0.002.

Results: Total number of respiratory adverse events in treatment period (6 weeks)

BT vs. either comparator (3 trials): BT: 1113/257; control: 369/164, p value not stated.

Results: Total number of respiratory adverse events in post‑treatment period (6 weeks to 1 year)

No increase with BT (data not shown).

Results: Hospitalisations for adverse respiratory events during treatment period

BT: 24/257,^a control: 4/164;^a RR 3.78 (95% CI 1.39 to 10.24); p=0.009.

Results: Hospitalisations for adverse respiratory events during post‑treatment period

BT: 11/257, ^a control: 7/164; ^a RR 1.15 (95% CI 0.47 to 2.79); NS.

Results: NNH for hospitalisations for adverse respiratory events with BT

15 per year (95% CI 5 to 106).

Conclusions

BT significantly improved morning PEF and quality of life at 12 months post‑treatment, and was generally well tolerated and safe. The increased risk of transient adverse events after BT was outweighed by the benefits of BT that lasted for more than 1 year. Additional long‑term RCTs are required to evaluate further the efficacy and safety of BT.

Abbreviations: AQLQ, Asthma Quality of Life Questionnaire; BT, bronchial thermoplasty; CI, confidence interval; ITT, intention to treat; NNH, number needed to harm; NS, not significant; PEF, peak expiratory flow; RCT, randomised controlled trial; RR, relative risk; WMD, weighted mean difference.

^aDenominator excludes patients lost to follow‑up.

Study component

Description

Objectives/hypotheses

Evaluate the long‑term efficacy and safety of BT for patients with moderate to severe asthma.

Study design

Systematic review and meta‑analysis.

Inclusion/exclusion criteria

Clinical trials including adults with moderate to severe persistent asthma who had received BT at least once using Alair system.

Primary outcomes

Pre‑ and post‑bronchodilator FEV₁, adverse respiratory events, ER visits and hospitalisations for adverse events.

Statistical methods

ITT analysis; heterogeneity assessed; when hypothesis of homogeneity was not rejected, a fixed‑effects model used; otherwise random effects model used.

Participants

3 RCTs (n=249 at 1 year and n=216 at 5 years).

Results: Change between end of year 5 and end of year 1 in pre‑bronchodilator FEV₁

WMD ‑0.75, 95% CI ‑3.36 to +1.85, p=0.57.

Results: Change between end of year 5 and end of year 1 in post‑bronchodilator FEV₁

WMD ‑0.62, 95% CI ‑3.32 to +2.08, p=0.65.

Results: Change between end of year 5 and end of year 1 in ER visits for respiratory adverse events

RR 1.06, 95% CI 0.77 to 1.46, p=0.71.

Results: Change between end of year 5 and end of year 1 in hospitalisation for respiratory adverse events

RR 1.47, 95% CI 0.69 to 3.12, p=0.32.

Results: Number of adverse events among patients at year 5 compared to year 1

Year 5: 201/1715 (12%) vs. year 1: 686/1715 (40%); RR 3.41, 95% CI 2.96 to 3.93, p<0.01.^a

Results: Number of people who experienced adverse events

Year 5 111/216 (51%) vs. year 1 184/249 people (74%).

Conclusions

The authors state that these data demonstrate reasonable long‑term benefits of BT with regard to safety and efficacy for patients with moderate to severe asthma. A large clinical study is required to confirm findings.

Abbreviations: BT, bronchial thermoplasty; CI, confidence interval; ER, emergency room; FEV₁, forced expiratory volume in 1 second; ITT, intention to treat; NS, not significant; RCT, randomised controlled trial; RR, risk ratio; WMD, weighted mean difference.

^aDenominator for the comparison is reported as 1715 at both 1 year and 5 years, but there were only 249 patients at 1 year and 216 patients at 5 years, so it is unclear what the denominator represents.