Medical Policy: 02.01.45 

Original Effective Date: July 2011 

Reviewed: February 2018 

Revised: February 2018 

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

Asthma, a chronic lung disease, affects approximately 7.6% of adults and 8.4% of children in the United States. Asthma symptoms include episodic shortness of breath that is generally associated with other symptoms such as wheezing, chest tightness and coughing. There is substantial heterogeneity in the inflammatory features of patients diagnosed with asthma, and this biologic diversity is responsible, at least in part, for the variable response to treatment in the asthma population. Most patients with asthma have mild to moderate disease and can be easily controlled by regular use of inhaled corticosteroids (ICS) combined with short acting inhaled B2 agonists for relief of symptoms. However, some patients asthma continues to be poorly controlled in terms of ongoing symptoms, frequent exacerbations, persistent and variable airway obstruction, and frequent requirements for B2 agonists despite aggressive treatment.

 

The goal of the treatment of asthma is to achieve and maintain clinical control by eliminating symptoms during both the day and night, to normalize measures of lung function, and to reduce the risk of exacerbations.

 

Management of asthma consists of environmental control, patient education, management of comorbidities, and regular follow up for all affected patients, as well as a stepped approach to medication treatment. Despite this multidimensional approach, many patients continue to experience considerable morbidity. In addition to ongoing efforts to optimally implement standard approaches to asthma treatment, new therapies are being developed, and bronchial thermoplasty is a potential treatment option for patients with severe persistent asthma.

 

Bronchial thermoplasty is based on the premise that patients with asthma have an increased amount of airway smooth muscle (ASM) and the contraction of this airway smooth muscle (ASM) is a major cause of airway constriction. The thermal energy delivered (radiofrequency) via bronchial thermoplasty aims to reduce the amount of airway smooth muscle (ASM) and thereby decrease muscle mediated bronchoconstriction with the ultimate goal of reducing asthma-related morbidity. Bronchial thermoplasty is intended as a supplemental treatment for patients with severe persistent asthma.

 

During the procedure a standard flexible bronchoscope is placed through the patient’s mouth or nose into the distal targeted airway and a catheter is inserted into the working channel of the bronchoscope. After placement, the electrode array in the top of the catheter is expanded, and radiofrequency energy is delivered from a proprietary controller used to heat tissue to 65 degrees Celsius over a 5 mm area. The positioning of the catheter and application of thermal energy is repeated several times in contiguous areas along the accessible length of the airway. At the end of the treatment session, the catheter and bronchoscope are removed.

 

After the first treatment session, previously treated airways are evaluated by bronchoscopy before proceeding with further treatment. A course of treatment consists of 3 separate procedures in different regions of the lung scheduled about 3 weeks apart (the first two sessions target the right lower lobe and left lower lobe separately while the final session targets the bilateral upper lobes). The procedure is performed on an outpatient basis with conscious sedation and requires approximately 1 hour to complete.

 

Three industry sponsored randomized controlled trials (RCTs) on bronchial thermoplasty have been published (AIR, RISA, AIR2) for the treatment of asthma. The largest RCT with the most rigorous methodology was the AIR2 trial. This was the only published trial that was double blinded and sham controlled, and also the only published RTC with sites in the United States.

 

AIR2 was an RCT evaluating the efficacy of bronchial thermoplasty at 30 sites in 6 countries (including the United States); findings were published in 2010 by Castro et al. Unlike the other 2 RCTs, the control condition was a sham intervention, and the trial was double-blind. Eligibility criteria were similar to those in the AIR trial; key differences were that a higher initial dose of ICSs was required (equivalent to at least 1000 μg beclomethasone), and patients were required to have experienced at least 2 days of asthma symptoms during the 4-week baseline period and have a baseline score on the Asthma Quality of Life Questionnaire (AQLQ) of no more than 6.25. (The possible range of the AQLQ score is 1 to 7, with a higher number representing a better QOL.) Also different from the AIR trial, patients were not required to experience symptom worsening during a period of abstinence from LABAs. Patients were stable on their asthma medication and continued their regimens during the study. The primary outcome was the difference between groups in the change from baseline in the AQLQ score, with scores from the 6-, 9-, and 12-month follow-ups averaged (integrated AQLQ score). A related outcome was the proportion of patients who achieved a change in their AQLQ score of 0.5 or greater, generally considered the minimally important difference for this scale. Bayesian analysis was used. The target posterior probability of superiority (PPS) of bronchial thermoplasty over sham was 95%, except for the primary AQLQ end point; there the target was 96.4% to adjust for 2 interim looks at the data.

 

A total of 297 patients were randomized, 196 to a bronchial thermoplasty group and 101 to a sham control group. The intervention for all participants consisted of 3 bronchoscopy procedures, performed 3 weeks apart. Participants and outcome assessment was blinded, but the intervention team was unblinded. The sham intervention was identical to the active treatment, except that no radiofrequency energy was delivered. Nine participants withdrew consent before beginning treatment, and 288 underwent bronchoscopy and were included in the intention-to-treat (ITT) population. One hundred eighty-five participants in the treatment group and 97 in the sham control group underwent the second bronchoscopy, and the same numbers of patients had the third bronchoscopy (it is not clear whether they were exactly the same patients). A total of 278 (94%) of the 297 enrolled patients completed the 12-month visit, 181 in the treatment group and 97 in the sham control group.

 

The superiority of bronchial thermoplasty was not achieved in the ITT population for the primary effectiveness outcome, mean change in the integrated AQLQ score. Mean (SD) change was 1.35 (1.10) in the bronchial thermoplasty group and 1.16 (1.23) in the sham control group. Using Bayesian analysis, the PPS was 96%. This did not surpass the target PPS of 96.4%. However, superiority of bronchial thermoplasty on a related outcome was achieved. In the ITT population, the percentage of patients achieving an AQLQ score change of 0.5 or greater (ie, at least the minimally important difference) was 79% in the bronchial thermoplasty group and 64% in the control group. The PPS at 99.6% surpassed the target probability for secondary outcomes of 95%. Additional analysis of data from the active treatment group suggested that responders (defined as a change in AQLQ score of at least 0.5) were more likely to have a lower baseline score than non-responders (mean, 4.1 vs 5.1, respectively).

 

Several secondary outcomes favored bronchial thermoplasty over the sham control group. They include a reduction in the proportion of patients reporting asthma worsening during follow-up (27.3% vs 42.9%, respectively; PPS=99.7%) and a reduction in the number of emergency department visits (0.07 vs 0.43 visits per person per year, respectively; PPS=99.9%). Moreover, there was a reduction in severe exacerbations of 0.47 per person per year in the bronchial thermoplasty group compared with 0.70 per person per year in the control group (PPS=95.5%). There were no significant differences between groups in other secondary efficacy outcomes, including morning peak expiratory flow, number of symptom-free days, symptom score, and rescue medication use.

 

For safety outcomes, during the treatment phase, there was a higher rate of respiratory adverse events in the active treatment group (85% of participants; mean, 1.0 events per bronchoscopy) compared with the sham group (76% of participants; mean, 0.7 events per bronchoscopy). A total of 16 (8.4%) patients in the active treatment group required 19 hospitalizations for respiratory symptoms during the treatment phase compared with 2 (2%) patients in the sham group, who required 1 hospitalization each. However,
during the posttreatment period, 70% of patients in the bronchial thermoplasty group and 80% of patients in the sham group reported adverse respiratory events. During this phase of the trial, 5 (2.6%) patients in the bronchial thermoplasty group had a total of 6 hospitalizations for respiratory symptoms, and 4 (4.1%) patients in the sham group had 12 hospitalizations (1 patient had 9 hospitalizations).

 

In the AIR2 trial, the sham group had a relatively high rate of response (eg, 64% experienced a clinically significant increase in the AQLQ score). Blinding appeared to be initially successful and remained so for the sham group. Participants in both groups were unable to correctly guess their treatment group after the first bronchoscopy. During subsequent assessments, this continued among patients in the sham group, whereas in the bronchial thermoplasty group, a larger proportion guessed correctly.

 

Two- and 5-year follow-up data on patients in the treatment group of the AIR2 trial have been published. In 2011, Castro et al reported 2-year data on 166 (87%) of 190 patients randomized to the bronchial thermoplasty group. In the second year after treatment, the proportion of participants who experienced severe exacerbations was 23.0% (95% confidence interval [CI], 16.6% to 29.5%). This compares with a 30.9% (95% CI, 24.2% to 37.7%) rate of exacerbations during year 1. The proportion who experienced asthma adverse events was 28.7% (95% CI, 22.1% to 35.3%) in year 1 and 26.5% (95% CI, 19.8 to 33.2) in year 2. In 2013, Wechsler et al reported 5-year data on 162 patients in the AIR2 trial (85% of those randomized to the treatment group).10 In a matched-pair analysis including the 162 study completers and the same group in previous years, the rate of severe exacerbations in years 1, 2, 3, 4, and 5 were 30.9%, 23.5%, 34.0%, 36.4%, and 21.6%, respectively. The proportion of patients experiencing severe exacerbations in years 2, 3, 4, and 5 did not differ significantly from the number of exacerbations in year 1. The proportion of patients who experienced asthma adverse events (at least > 2 asthma symptoms occurring at the same time) were 28.7%, 27.9%, 29.6%, 31.4%, and 24.7%, respectively. The proportion of patients with at least 1 hospitalization for respiratory adverse events these same years was 3.3%, 4.2%, 6.2%, 5.7%, and 1.9%, respectively. In the 12 months before bronchial thermoplasty, the rate of hospitalization for respiratory symptoms in this group was 4.2%. These follow-up studies are limited in that follow-up data were not collected on patients randomized to the sham group, and therefore outcomes (eg, rate of exacerbations, rate of hospitalizations) cannot be compared in patients who did and did not receive bronchial thermoplasty.

 

The results of the AIR-2 trial have generated enormous interest, controversy, and confusion regarding the true efficacy of bronchial thermoplasty for severe asthma. The FDA approved bronchial thermoplasty for the treatment of adults with severe asthma and this approval was based on the results of the AIR-2 trial. Current marketing of bronchial thermoplasty highlights its use for adult patients with severe and persistent asthma, which is interpreted by most clinicians as meaning oral corticosteroid dependence, frequent exacerbations, or a significantly reduced FEV1 with poor quality of life (QOL). However, these types of patients were specifically excluded from the AIR-2 trial which raises questions about the efficacy of bronchial thermoplasty.

 

Systematic Reviews

Several pooled analyses of the 3 published RCTs were identified. Most recently, in 2016, Zhou et al published a systematic review of the published RCTs and extension studies, focusing on the durability and long-term responses for treated patients. Reviewers pooled data on long-term effects in bronchial thermoplasty treated patients only (i.e. not in comparison groups). In an analysis of 216 patients with 5 years of follow-up, there was no significant decline in spirometry-detected prebronchodilator FEV1 (percent predicted) compared with 1-year findings (weighted mean difference [WMD], 0.75; 95% CI, -3.36 to 1.85; p=0.57 ; I2=0%). Similarly, there was no significant decline in postbronchodilator FEV1 (WMD=0.62; 95% CI, -3.32 to 2.08; p=0.65; I2=0%). In terms of adverse events over time, the rates of respiratory adverse events, emergency department visits for adverse events, and hospitalizations did not differ significantly after the 1- and 5-year follow-ups.

 

In 2011, Wu et. al. published a meta-analysis of the findings of the 3 published RCTs. Pooled analyses of them found greater mean improvement in asthma QOL in the bronchial thermoplasty groups than in the control groups (WMD=0.63; 95% CI, 0.10 to 1.15) and greater improvement in the peak expiratory flow with bronchial thermoplasty treatment than with the control treatment (WMD=21.78; 95% CI, 8.06 to 35.50). During the treatment period (beginning on the day of the first treatment session and lasting 6 weeks after the last session), there were more respiratory adverse events in the bronchial
thermoplasty groups (1113 events in 257 patients) than in the control groups (369 events in 164 patients) (p value not reported). Also during the treatment period, there was a significantly higher risk of hospitalization with bronchial thermoplasty than with control (RR=3.78; 95% CI, 1.39 to 10.24). In the posttreatment period (end of treatment to the 12-month follow-up visit), there was no significant difference between groups in the risk of hospitalization (RR=1.15; 95% CI, 0.47 to 2.79).

 

In 2014, a Blue Cross Blue Shield Association TEC Assessment was published on bronchial thermoplasty for treatment of inadequately controlled severe persistent asthma. The Assessment included the 3 published RCTs (AIR, RISA, AIR2) and concluded, “the evidence is insufficient to determine whether potential improvements in some outcomes, but not others defining the net health outcome, outweigh the potential harms” and that the technology did not meet TEC criteria.

 

In 2014, a Cochrane review of RCTs was published by Torrego et. al. reviewers included the 3 RCTs. Potential trial limitations identified by reviewers were lack of blinding in 2 of the 3 trials and lack of a sham control in 2 trials. Pooled analyses were not conducted for asthma exacerbation outcomes. A meta-analysis of the 3 trials found significantly greater improvement in AQLQ scores at 12 months in the bronchial thermoplasty groups than in the control groups (mean difference [MD], 0.28; 95% CI, 0.07 to 0.40). However, at 12 months, the proportion of patients using rescue medication did not differ significantly between groups (MD = -0.68; 95% CI, -3.63 to 2.28). In terms of adverse events, a significantly higher number of patients were admitted to the hospital for respiratory events during the treatment period (relative risk [RR], 3.50; 95% CI, 1.26 to 9.68). There was no significant difference between groups in the proportion of patients admitted to the hospital for respiratory events in the posttreatment period (RR=1.12; 95% CI, 0.44 to 2.85).

 

In 2017, Chupp et. al. compared outcomes in bronchial thermoplasty subjects with 3 years of follow-up from the ongoing, post-market PAS2 (Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma) study with those from the AIR2 trial. Bronchial thermplasty is an endoscopic therapy for severe asthma. The previously reported, randomized sham-controlled AIR2 (Asthma Intervention Research 2) trial showed a significant reduction in severe asthma exacerbations, emergency department visits, and hospitalizations after bronchial thermoplasty. More “real world” clinical outcome data is needed. 279 subjects were treated with bronchial thermoplasty in the PAS2 study. The reviewers compared the first 190 PAS2 subjects with the 190 bronchial thermoplasty treated subjects in the AIR2 trial at 3 years follow-up. The PAS2 subjects were older (mean age 45.9 versus 40.7 years) and more obese (mean body mass index 32.5 versus 29.3 kg m2 and took higher doses of corticosteroids (mean dose 2301 versus 1961 ug/day). More PAS2 subjects had experienced severe exacerbations (74% versus 52%) and hospitalizations (15.3% versus 4.2%) in the 12 months prior to bronchial thermoplasty. At year 3 after bronchial thermoplasty, the percentage of PAS2 subjects with severe exacerbations, emergency department visits and hospitalizations significantly decreased by 45%, 55% and 40%, respectively, echoing the AIR2 results. The authors concluded The PAS2 study subjects described in this article appear to be slightly sicker than the subjects in the AIR2 trial based on baseline characteristics. The PAS2 study shows, similar to the AIR2 trial, that bronchial thermoplasty is safe and that subjects have markedly lower rates of steroid exacerbations, hospitalizations and emergency department visits at 3 years after bronchial thermoplasty compared with the 12 months prior to bronchial thermoplasty treatment, and that the treatment effect is consistent and durable. The study subjects also sustainably reduced their asthma medication, including complete discontinuation of maintenance OCSs for a significant number of subjects. Notably the PAS2 study is a prospective nonrandomized clinical study, and comparing its results to a randomized controlled trial is challenging due to potential for exogenous bias and confounding factors outside those baseline demographics and clinical characteristics measured. Notwithstanding these caveats, this study offers useful results to clinicians convinced of the efficacy of bronchial thermoplasty within the confines of a randomized controlled trial, but who questioned its “real world” clinical benefits. Although the prospectively enrolled PAS2 study population in this article is described as “real world”, the study eligibility criteria mean that the most severe subjects often seen in clinical practice were not included. Nevertheless, the 3 year results from this subset of subjects in the PAS2 study inspire confidence, because they suggest that the “real world” results obtained after bronchial thermoplasty in the PAS2 study echo those observed in the AIR2 randomized controlled trial.

 

In 2017, Agency for Healthcare Research and Quality (AHRQ) issued a comparative effectiveness review on the effectiveness and safety of bronchial thermoplasty in the management of adults with asthma. Data sources included five bibliographic databases, MEDLINE, Embase, PubMed, CINAHL, and Cochrane Library, through April 20, 2017. Eligible studies included systematic reviews, meta-analyses, randomized controlled trials (RCTs), and nonrandomized interventional studies with concurrent controls. Case reports and case series were also considered for describing adverse events. Fifteen studies, including three RCTs with 5-year single arm follow-up in bronchial thermoplasty (BT) treated patients (n=432 for the RCTs), examined the impact of BT in addition to standard care (continued medical management) on patients with asthma. BT and standard of care improved asthma control (defined by the Asthma Control Questionnaire (ACQ) change from baseline to 12 months) and Asthma Quality of Life Questionnaire (AQLQ) scores more than standard care alone to a degree that was statistically significant but not clinically important (low strength of evidence). However, BT and standard care, compared with a sham bronchoscopic procedure and standard care, did not improve asthma control (defined as ACQ change from baseline to 12 months), hospitalizations for respiratory symptoms, use of rescue medications, pulmonary physiology measures, or AQLQ scores (in the intention to treat analysis), low strength of evidence. In the sham-controlled trial, BT reduced severe exacerbations after the 12-week treatment period to a statistically but not clinically important degree (low strength of evidence), and patients undergoing BT had fewer emergency department visits than patients who had the sham bronchoscopic procedure (moderate strength of evidence). In the RCTs comparing BT and standard care alone, evidence was insufficient to assess if BT reduced rates of severe exacerbations. Common adverse events following BT during the 12 week treatment period in the RCTs included bronchial irritation, chest discomfort, cough, discolored sputum, dyspnea, night awakenings, and wheezing. Hospitalizations were more common in patients undergoing BT than with either standard care alone or sham bronchoscopy during the 12 week treatment period as were upper respiratory tract infections, wheezing, dyspnea, lower respiratory tract infections, anxiety, and segmental atelectasis, but the events were to infrequent to achieve statistical significance. Severe adverse events (including post-procedure segmental atelectasis due to mucus plugging, hemoptysis, chest infections requiring hospitalization, and bronchial artery pseudoaneurysm) were also reported in six case reports and two small case series. Following the 12 week treatment period, rates of respiratory related hospitalizations were not significantly different between groups for up to 5 years of follow-up. No deaths were attributed to BT. The authors concluded while asthma control and quality of life measures modestly improved in patients undergoing BT compared to medical management alone in two controlled but non-blinded studies, these measures did not improve in the sham-controlled study. The sham-controlled, blinded study found modest improvements in severe exacerbations and significantly fewer emergency department visits following BT compared to the sham bronchoscopic procedure, but serious adverse events and post-procedure hospitalization were common during the 12 week treatment period in patients undergoing BT than in patients undergoing sham treatment. The available body of literature on BT is small and uncertainty remains about appropriate patient selection criteria and the effects of the treatment beyond 5 years.

Case Series

After publication of the 3 RCTs (AIR, RISA, AIR2), several case series have described outcomes in clinical practice. They generally had small sample sizes (eg, N=7,14 N=10,15 and N=2016). In addition, a rigorous U.K. registry study was published by Burn et al (2016), which focused on safety outcomes. The study combined data from 2 sources, the U.K. Difficult Asthma Registry and the Hospital Episode Statistics warehouse, and included patients treated with bronchial thermoplasty in the U.K. between June 2011 and January 2015. Eighty-three patients were identified in the Difficult Asthma Registry and 85 in the Hospital Episode Statistics database. For 59 patients, data in the 2 databases could be matched. Most patients had a course of 3 bronchial thermoplasty treatment sessions. Data from the matched cohort were used to calculate event rates for 4 binary safety outcomes. Procedural complications were reported in 17 (11%) of 152 procedures in 13 (22%) patients; emergency department readmissions within 30 days of the initial hospitalization were reported for 15 (11.8%) patients; and accident and emergency visits (i.e. emergency department) visits for any reason were reported for 13 (8.6%) patients. For the fourth binary outcome (post-procedure overnight stay), 70 (46.1%) of 152 procedures were followed by an overnight stay. In total, 20.4% of procedures in the matched cohort were associated with at least 1 of the 4 safety issues. The authors noted that the relatively high rate of safety events might be related to older patients with more severe disease being treated in clinical practice compared with patients included in clinical trials.

 

Summary

For individuals who have asthma refractory to standard treatment who receive bronchial thermoplasty, the evidence includes 3 randomized controlled trials (RTCs) a meta-analyses of these RCTs to include a recent (2017) review by AHRQ and case series. Relevant outcomes are symptoms, quality of life, hospitalizations, and treatment-related morbidity. The AIR2 trial is the largest of the 3 published RCTs, and the only one double-blinded and sham-controlled, with sites in the United States. Over 1 year, bronchial thermoplasty was not found to be superior to sham treatment on the investigator-designed primary efficacy outcome of mean change in quality of life (QOL) score, but was found to be superior on a related outcome, improvement in quality of life of at least 0.5 points on the Asthma Quality of Life Questionnaire (AQLQ). There was a high response rate in the sham group of the AIR2 trial, which suggests a large placebo effect, particularly for subjective outcomes such as quality of life. On the secondary outcomes, bronchial thermoplasty provided greater benefit than sham treatment on some, but not all, outcomes. In the AIR and RISA trials, there were improvements in quality of life (QOL) for the bronchial thermoplasty group compared to the medical management group. However, given the lack of benefit in the AIR2 trial, it is possible that the difference in quality of life (QOL) for these 2 trials were due at least in part to a placebo effect. Findings on adverse events from the 3 trials have suggested that bronchial thermoplasty is associated with a relatively high rate of adverse events, including hospitalizations during the treatment period and several weeks afterwards. Safety data from a U.K. registry study, published in 2016, found that 20% of bronchial thermoplasty procedures were associated with a safety event (i.e. procedural complications, emergency respiratory readmissions, emergency department visits, and/or post-procedure overnight stays).

 

While studies may show beneficial results for bronchial thermoplasty in the management of some patients with asthma, with benefit typically observed weeks to months after therapy and can last for at least 5 years, after which the duration of effect is unknown, conclusions cannot be drawn about the effect of bronchial thermoplasty on the net health outcomes due to the limited evidence consisting of only one RTC that used a sham control. Further studies are needed using sham comparison to strengthen the evidence and help guide the appropriate use of bronchial thermoplasty and to identify the patients most likely to respond to this therapy to include if bronchial thermoplasty is more effective in certain asthma phenotypes (e.g. eosinophilic, neutrophilic, paucigranulocytic). Also, the risk of adverse events is higher during the treatment period and for several weeks afterwards. Support by professional societies/organizations in the form of published consensus statements or guidelines is variable. The European Respiratory Society (ERS) and the American Thoracic Society (ATS) guideline states “bronchial thermoplasty performed in adults with severe asthma should only be in the context of an Institutional Review Board approved independent systemic registry of a clinical study.” There is insufficient and low quality evidence regarding the use of bronchial theramoplasty in patients with severe asthma who are resistant to standard therapies. The evidence is insufficient to determine the effects of bronchial thermoplasty on net health outcomes for the treatment of asthma.

 

Practice Guidelines and Position Statements

American College of Allergy, Asthma and Immunology (ACCAI)

In a 2015 statement on bronchial thermoplasty the ACAAI notes: “Bronchial thermoplasty is a well-studied treatment for patients with very severe asthma who continue to be symptomatic despite maximal medical treatment including steroids, long-acting beta agonists (LABAs), long-acting muscarinic agents (LAMAs), leukotriene antagonists and biologics. The device to deliver this therapy is FDA approved. The scientific literature supports bronchial thermoplasty as a therapeutic consideration for some carefully chosen patients with severe asthma. Carefully selected patients with severe persistent asthma who have persistent burden of disease, asthma exacerbations, emergency department visits or hospitalizations despite maximal medical treatment may benefit from this procedure. Therefore, ACAAI recommends that insurers provide coverage for bronchial thermoplasty for those adult patients who meet the stringent requirements.”

 

National Institute of Health and Clinical Excellence (NICE)

In 2012 NICE published a guideline IPG419 bronchial thermoplasty for severe asthma. The guideline notes that evidence on the efficacy of bronchial thermoplasty for severe asthma shows improvement in symptoms and quality of life, and reduced exacerbations and admission to hospital. Evidence on safety is adequate in the short and medium term. More evidence is required on the safety of the procedure in the long term. Therefore, ths procedure should only be used with special arrangements for clinical governance, consent and audit for research. NICE encourages further research into bronchial thermoplasty for severe asthma. Research outcomes should include objective measurements of lung function, symptom control, medication requirements and quality of life. Long-term safety and efficacy outcomes are particularly important.

 

In 2015 NICE published Individual Research Recommendation Details regarding IPG419 that notes: NICE encourages further research into bronchial thermoplasty for severe asthma. Research outcomes should include objective measurements of lung function, symptom control, medication requirements and quality of life. Long-term safety and efficacy outcomes are particularly important.

 

Evidence on the efficacy of bronchial thermoplasty for severe asthma shows improvement in symptoms and quality of life, and reduced exacerbations and admission to hospital. Evidence on safety is adequate in the short and medium term. More evidence is required on the safety of the procedure in the long term. Therefore, ths procedure should only be used with special arrangements for clinical governance, consent and audit for research.

 

Global Initiative for Asthma (GINA)

GINA is an international network of organizations and professionals with expertise in asthma. The group has been updating a report entitled Global Strategy for Asthma Management and Prevention annually since 2002, the most recent update was issued in 2017. GINA recommends stepped care for the treatment of asthma. Step 1 consists of reliever inhaler use on an as needed basis. Step 2 involves low dose controller medication plus as needed reliever medication. Step 3 includes one or two controllers plus as needed reliever medication. Step 4 is two or more controllers plus as needed reliever medication. Step 5 involves higher level of care and/or add-on treatment.

 

According to the GINA document, options for add-on treatment include bronchial thermoplasty for some adults with severe asthma (Evidence B). The document also notes the following:

  • Evidence on bronchial thermoplasty is limited and in selected patients. The long term effects compared with control patients including lung function are not known.
  • Longer term follow up of larger cohorts comparing effectiveness and safety, including for lung function, in both active and sham treated patients is needed. Caution should be used in selecting patients for this procedure. The number of studies is small, and people with chronic sinus disease, frequent chest infections or FEV1 <60% predicted were excluded from the sham-controlled study.
  • The 2014 ERS/ATS (European Respiratory Society and American Thoracic Society) Task Force on Severe Asthma recommends that bronchial thermoplasty should be performed in adults with severe asthma only in the context of an independent Institutional Review Board approved with systematic registry or a clinical study, so further evidence about effectiveness and safety of the procedure can be accumulated.

 

American College of Chest Physicians (ACCP)

In May 2014, ACCP posted a position statement on Coverage and Payment for Bronchial Thermoplasty for Severe Persistent Asthma. The document states in part,

 

“CHEST believes that based on the strength of the clinical evidence, bronchial thermoplasty offers an important treatment option for adult patients with severe asthma who continue to be symptomatic despite maximal medical treatment and, therefore should not be considered experimental. Randomized controlled trials of bronchial thermoplasty for severe asthma have shown a reduction in the rate of severe exacerbations, emergency department visits, and days lost from school or work. Additionally, data published in December 2013 demonstrates the persistence of reduction in asthma symptoms achieved by bronchial thermoplasty for at least 5 years…”

 

European Respiratory Society (ERS) and American Thoracic Society (ATS):

In 2014, a joint task force of the European Respiratory Society and American Thoracic Society published guidelines on the definition, evaluation and treatment of severe asthma. The guideline was based on a systematic review of the literature. It includes the statements:

  • “We recommend that bronchial thermoplasty (BT) is performed in adults with severe asthma only in the context of an Institutional Review Board-approved independent systematic registry of a clinical study.” The authors remarked: “This is a strong recommendation, because of the very low confidence in the available estimates of effects of BT in patients with severe asthma.”
  • “Both potential benefits and harms may be large and the long term consequences of this new approach to asthma therapy utilizing an invasive physical intervention are unknown.”
  • “Specifically designed studies are needed to define its effects on relevant objective primary outcomes such as exacerbation rates, and on long term effects on lung function.”
  • “Studies are also needed to better understand the phenotypes or responding patients, its effects on patients with severe obstruction asthma (FEV1 <60% of predicted value) or in whom systemic corticosteroids are used, and its long-term benefits and safety.”
  • “Further research is likely to have an important impact on this recommendation.”

 

British Thoracic Society and Scottish Intercollegiate Guidelines Network

In 2016, the British Thoracic Society and the Scottish Intercollegiate Guidelines Network published a revised national guideline on management of asthma. The guideline states:

  • Bronchial thermoplasty may be considered for the treatment of adult patients who have poorly controlled asthma despite optimal therapy.
  • Assessment and treatment for bronchial thermoplasty should be undertaken in centers that have expertise in the assessment of difficult to control asthma and in fiberoptic bronchoscopic procedures.
  • The balance of risks and benefits of bronchial thermoplasty treatment should be discussed with patients being considered for the procedure.
  • Longer term follow up of treated patients is recommended
  • Further research is recommended into factors that identify patients who will or will not benefit from bronchial thermoplasty treatment.

 

Regulatory Status

In April 2010, the Alair® Bronchial Thermoplasty System (Asthmatx, Inc. Sunnyvale, CA, now part of Boston Scientific Corp.) was approved by the U.S. Food and Drug Administration (FDA) through the premarket approval (PMA) process for the use in adults with severe and persistent asthma whose symptoms are not adequately controlled with inhaled corticosteroids and long acting beta agonists. The labeling also lists the following contraindications:

 

Patients with the following conditions should not be treated:

  • Presence of a pacemaker, internal defibrillator, or other implantable electronic devices
  • Known sensitivity to medications required to perform bronchoscopy, including lidocaine, atropine and benzodiazepines
  • Patients previously treated with the Alair System should not be retreated in the same area(s). No clinical data are available studying the safety and/or effectiveness of repeat treatments.

 

Patients should not be treated while the following conditions are present:

  • Active respiratory infection
  • Asthma exacerbation or changing dose of systemic corticosteroids for asthma (up or down) in the past 14 days
  • Known coagulopathy
  • As with other bronchoscopic procedures, patients should stop taking anticoagulants, antiplatlet agents, aspirin and NSAIDS before the procedure with physician guidance.

 

Prior Approval:

Not applicable

 

Policy:

Bronchial thermoplasty is considered investigational for all indications, including but not limited to the treatment of asthma.

 

While studies may show beneficial results for bronchial thermoplasty in the management of some patients with asthma, with benefit typically observed weeks to months after therapy and can last for at least 5 years, after which the duration of effect is unknown, conclusions cannot be drawn about the effect of bronchial thermoplasty on the net health outcomes due to the limited evidence consisting of only one RTC that used a sham control. Further studies are needed using sham comparison to strengthen the evidence and help guide the appropriate use of bronchial thermoplasty and to identify the patients most likely to respond to this therapy to include if bronchial thermoplasty is more effective in certain asthma phenotypes (e.g. eosinophilic, neutrophilic, paucigranulocytic). Also, the risk of adverse events is higher during the treatment period and for several weeks afterwards. Support by professional societies/organizations in the form of published consensus statements or guidelines is variable, the European Respiratory Society (ERS) and the American Thoracic Society (ATS) guideline states “bronchial thermoplasty performed in adults with severe asthma should only be in the context of an Institutional Review Board approved independent systemic registry of a clinical study.” There is insufficient and low quality evidence regarding the use of bronchial theramoplasty in patients with severe asthma who are resistant to standard therapies. The evidence is insufficient to determine the effects of bronchial thermoplasty on net health outcomes for the treatment of asthma.

 

Procedure Codes and Billing Guidelines:

  • To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
  • 31660 Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with bronchial thermoplasty, 1 lobe
  • 31661 Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with bronchial thermoplasty, 2 or more lobes     

 

Selected References:

  • Castro M, Rubin AS, Laviolette M et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med 2010; 181(2):116-24.
  • Cox G, Thomson NC, Rubin AS et al. Asthma control during the year after bronchial thermoplasty. N Engl J Med 2007; 356(13):1327-37.
  • Pavord ID, Cox G, Thomson NC et al. Safety and efficacy of bronchial thermoplasty in symptomatic severe asthma. Am J Resir Crit Care Med 2007; 176(12):1185-91.
  • Thomson NC, Rubin AS, Niven RM et al. Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial. BMC Pulm Med 2011; 11:8.
  • Canadian Agency for Drugs and Technologies in health (CADTH). Bronchial thermoplasty: A hot approach to asthma treatment? Health Technol Update. 2007;6:5.
  • Cox G. Bronchial thermoplasty. Clin Chest med. 2010;31(1):135-40.
  • Wechsler ME. Bronchial thermoplasty for asthma: A critical review of a new therapy. Allergy Asthma Proc. 2008;29(4):365-70.
  • Castro M, Rubin A, Laviolette M et al. Persistence of effectiveness of bronchial thermoplasty in patients with severe asthma. Ann Allergy Asthma Immunol. 2011 Jul; 107(1):65-70. Epub 2011 Apr 14.
  • Gildea TR, Khatri SB, Castro M. Bronchial thermoplasty: a new treatment for severe refractory asthma. Cleve Clin J Med. 2011 Jul; 78(7):477-85.
  • ECRI Institute. Plymouth Meeting (PA): Emerging Technology Evidence Report. Bronchial Thermoplasty for treatment of adult patients with severe persistent asthma. January 2012. 
  • Jilcy M, Theraputic option for severe asthma. Arch Med Sci. 2012 September 8; 8(4): 589-597.
  • ECRI. Product Brief. Alair Bronchial Thermoplasty System (Boston Scientific, Inc) for Treating Asthma. January 2014.
  • National Institute for Health and Clinical Excellence. Bronchial Thermoplasty for Severe Asthma, Issued January 2012. guidance.nice.org.uk/ipg419
  • National Guideline Clearinghouse. British Thoracic Society Guideline for Advanced Diagnostic and Therapeutic Flexible Bronchoscopy in Adults, Du Rand IA, et al. November 2011.
  • MedPage Today. Meeting Coverage at the American Academy of Allergy, Asthma and Immunology meeting. Bronchial Thermoplasty in Asthma: Ready or Not? Published March 2, 2014.
  • American Academy of Allergy Asthma & Immunology, Bronchial Thermoplasty Provides Long Term Asthma Control, published online September 3, 2013.
  • MedScape Reference. Bronchial Thermoplasty, Mahmoud Mahafzah, MBBS, Zab Mosenifar, M.D. et al. Updated December 15, 2015. 
  • UpToDate. Treatment of Severe Asthma in Adolescents and Adults. Sally Wenzel, M.D.  Topic last updated January 311, 20146.
  • ECRI. Emerging Technology Report. Bronchial Thermoplasty (Alair System) for Treating Adult Patients with Severe Symptomatic Asthma. October 2014.
  • American College of Chest Physicians 2014 position statement for Coverage and Payment for Bronchial Thermoplasty for Severe Persistent Asthma. Also available at chestnet.org
  • Canadian Agency for Drugs and Technologies in Health (CADTH), Bronchial Thermoplasty for Severe Asthma: Clinical and Cost Effectiveness and Guidelines, March 27, 2014.
  • Medscape. Bronchial Thermoplasty for Asthma: 5 Year Efficacy Results. August 2013.
  • Medscape. Bronchial Thermoplasty: Interventional Therapy in Asthma, 2014.
  • Stephen Bickness, Rekha Chaudhuri and Neil C. Thomson, How to: Bronchial Thermoplasty in Asthma, Breath March 1, 2014 vol. 10 no. 1 48-59
  • UpToDate. Treatment of Severe Asthma in Adolescents and Adults, Sally Wenzel, M.D.. Topic last updated October 5, 2017.
  • American Academy of Allergy Asthma and Immunology Asthma Treatment and Management.
  • Global Initiative for Asthma (GINA) Global Strategy for Asthma Management and Prevention updated May 2014. 
  • BCBSA TEC Assessment, Bronchial Thermoplasty for Treatment of Inadequately Controlled Severe Asthma, December 10, 2014.
  • Wechsler Michael M.D., Laviolette Michel M.D., et. al. Bronchial Thermoplasty – Long Term Safety and Effectiveness in Severe Persistent Asthma. J Allergy Clin Immunol. 2013 December; 132(6): 1295-1302
  • National Heart Lung and Blood Insitute. Expert Panel Report 3: Guidelines for Diagnosis and Management of Asthma (EPR-3) 2007.
  • Pavod ID, Thomson NC, Niven RM, et. al. Safety or bronchial thermoplasty in patients with severe refractory asthma. Ann Allergy Asthma Immunol. Nov 2013;111(5):402-407. PMID 24125149
  • Torrego A, Sola I, Munoz AM, et. al. Bronchial thermoplasty for moderate or severe persistent asthma in adults. Cochrane Database Syst Rev. 2014;3:CS009910. PMID 24585221
  • Wu Q, Xing Y, Zhou X, et. al. Meta-analysis of the efficacy and safety of bronchial thermoplasty in patients with moderate-to-severe persistent asthma. J Int Med Res. 2011;39(1):10-22. PMID 21672303
  • GINA. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention (2015 Update).
  • Chung KF, Wenzel SE, Borzek JL, et. al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J Feb 2014;43(2):343-373. PMID 24337046
  • British Thoracic Society and Scottish Intercollegiate Guidelines Network, Guideline on Management of Asthma.
  • California Technology Assessment Forum. Bronchial thermoplasty for the treatment of severe asthma, published 2011 Oct 19.
  • Boston Scientific Corporation. Bronchial Thermoplasty.
  • Asthma and Allergy Foundation of American.
  • American Academy of Allergy, Asthma and Immunology. Conditions dictionary-bronchial thermoplasty.
  • American Academy of Allergy, Asthma and Immunology. Statement on bronchial thermoplasty. Also available at www/aaaai.org
  • Laxmanan B, Hogarth DK. Bronchial thermoplasty in asthma: current perspectives. J Asthma Allergy. 2015 May 15;8:39-49
  • National Institute of Health and Clinical Excellence (NICE), Interventional Procedure Guidance IPG419, Bronchial Thermoplasty for Severe Asthma, Published January 2012.
  • National Institute of Health and Clinical Excellence (NICE), Individual Research Recommendation Details, Published June 2015.
  • Iyer V, Lim K. Bronchial Thermoplasty Reappraising the Evidence (or Lack Thereof), Chest 2014;146(1):17-21
  • Centers of Disease Control and Prevention. Asthma FastStats.
  • Zhou JP, Fent Y, Wang Q, et.al. Long-term efficacy and safety of bronchial thermoplasty in patients with moderate to severe persistent asthma: a systemic review and meta-analysis. J Asthma Feb 2016;53(1):94-100 PMID 26383773
  • Castro M, Rubin AS, Laviolette M, et. al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double blind, sham-controlled clinical trial. AM J Respir Crit Care Med. Jan 15 2010;181(2):116-124. PMID 19815809
  • Zhou JP, Feng Y, Want Q, et. al. Long –term efficacy and safety of bronchial thermoplasty in patients with moderate-to-severe persistent asthma: a systemic review and meta-analysis. J Asthma. Feb 2016;53(1):94-100. PMID 26383773
  • Arrigo R, Failla G, Schichilone N, et. al. How effective and safe is bronchial thermoplasty in “real life” asthmatics compared to those enrolled in randomized clinical trials? Biomed Res Int. 2016;2016:9132198. PMID 21672303
  • Bicknell S, Chaudhuri R, Lee N, et. al. Effectiveness of bronchial thermoplasty in severe asthma in “real life” patients compared with those recruited to clinical trials in the same center. Ther Adv Respir Dis. Dec 2015;9(6):267-271. PMID 26307767
  • Langton D, Sha J, Ing A, et. al. Bronchial thermoplasty in severe asthma in Australia. Intern Med J. May 2017;47(5):536-541. PMID 28101900
  • Burn J, Sims AJ, Keltie K, et. al. Procedural and short-term safety of bronchial thermoplasty in clinical practice: evidence from a national registry and hospital episode statistics. J Asthma. Dec 01 2016:0 PMID 27905828
  • Centers for Disease Control and Prevention, National Center for Health Statistics. Asthma FastStats.
  • Laxmann B, Hogarth DK. Bronchial thermoplasty in asthma current perspectives. Journal of Asthma and Allergy 2015:8 39-49
  • Chupp G, Laviolette M, Cohn L, et. al. Long-term outcomes of bronchial thermoplasty in subjects with severe asthma: a comparison of 3-year follow-up results from two perspective multicenter studies. Eur Respir J 2014;50:1700017
  • Agency for Healthcare Research and Quality (AHRQ) Effectiveness and Safety and Bronchial Thermoplasty in Management of Asthma. Comparative Effectiveness Review Number 202. December 2017.  
  • ECRI. Effectiveness and Safety of Bronchial Thermoplasty in Management of Asthma (AHRQ). Published 12/14/2017.

 

Policy History:

  • February 2018 - Annual Review, Policy Revised
  • November 2017 - Interim Review, Policy Revised
  • February 2017 - Annual Review, Policy Renewed
  • February 2016 - Annual Review, Policy Revised
  • March 2015 - Annual Review, Policy Renewed
  • April 2014 - Annual Review, Policy Renewed
  • May 2013 - Annual Review, Policy Renewed
  • May 2012 - Annual Review, Policy Renewed
  • July 2011 - Evidence Review, New Policy

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

*CPT® is a registered trademark of the American Medical Association.