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Effective Date: 03/01/2013 |
Title: Bronchial Thermoplasty
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Revision Date:
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Document: BI393:00
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CPT Code(s): 31660, 31661
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Public Statement
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Bronchial thermoplasty is a newly available potential treatment option for patients with severe persistent asthma. It consists of radiofrequency energy delivered to the distal airways with the aim of decreasing smooth muscle mass believed to be associated with airway inflammation. This procedure has not been demonstrated to improve health outcomes in patients with asthma, and is considered by QualChoice to be investigational.
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Medical Statement
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Bronchial thermoplasty for the treatment of asthma or any other condition is considered investigational as there is a lack of scientific evidence of effectiveness in improving health outcomes. Codes Used in This Policy: 31660 Bronchial thermoplasty one lobe 31661 Bronchial thermoplasty two or more lobes
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Background
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Research in Severe Asthma (RISA) trial: This study, published by Pavod and colleagues in 2007, was conducted at 8 centers in the U.K., Brazil and Canada (Pavord, 2007). Eligibility criteria included age 18 or older; asthma diagnosis; uncontrolled symptoms despite treatment with high-dose inhaled corticosteroids (at least 750 ug fluticasone propionate per day or equivalent) and long-acting beta agonists (at least 100 ug salmeterol per day or equivalent), with or without other medications including oral prednisone or leukotriene modifiers; FEV-1 at least 50% of predicted; demonstrated airway hyperresponsiveness by challenge with methacholine or reversible bronchoconstriction during the prior 12 months; abstinence from smoking for at least 1 year and a past smoking history of less than 10 pack-years. After a 2-week run-in period, participants were randomized to a control group (n=17) that received continued medical management alone or medical management plus treatment with the Alair Bronchial Thermoplasty System (n=17). The bronchial thermoplasty group received 3 procedures at least 3 weeks apart (weeks 0-6). During weeks 6-22, all participants remained on a stable dose of steroids and then during weeks 22-36, in attempt was made to reduce the dose of oral corticosteroids (or inhaled corticosteroids for patients not taking the oral medication). Between weeks 36 to 52, patients took the reduced dose of steroids. The primary outcomes of the study were the rate of adverse events and serious adverse events (defined as any event that was fatal, required or prolonged hospitalization, caused substantial immediate risk of death, resulted in permanent impairment or required intervention to prevent permanent impairment). A total of 32 of the 34 participants (94%) completed the study. In the initial treatment period, 4 patients in the bronchial thermoplasty group experienced 7 serious adverse events requiring hospitalization and none occurred in the control group. During the remainder of the study, 3 patients in the bronchial thermoplasty group experienced 5 serious adverse events and 1 patient in the control group experienced 4 serious adverse events; all of these events required hospitalization. There were an additional 5 severe adverse events in 2 bronchial thermoplasty group patients and 1 event in a control group patient that were medically treated without hospitalization (the authors did not report whether or not these were the same patients who were hospitalized). No overall statistical analysis was done comparing serious adverse events in the two groups. The authors also reported a number of efficacy variables as secondary outcomes. At the end of the study at 52 weeks, bronchial thermoplasty patients had a significantly greater improvement in beta-agonist use than control patients (decrease of 26 puffs versus 6 puffs per week, p<0.05) and there was no significant difference between groups in other efficacy variables including morning and evening peak expiratory flow, symptom scores, number of symptom-free days, improvement in FEV-1 predicted and several quality of life measures. The study was limited in its ability to accurately evaluate safety by a small sample size. Asthma Intervention Research (AIR) trial: Cox and colleagues published findings of the AIR trial in 2007; patients were recruited from the same 3 countries as the RISA study plus Denmark (Cox, 2007). The eligibility criteria included age 18-65 with moderate to severe persistent asthma requiring daily therapy with inhaledcorticosteroids (equivalent to at least 200 ug beclomethasone) and long-acting beta-agonists (at least 100ug salmeterol or equivalent). Also required for study entry were an FEV-1 of 60-85% predicted, airway hyperresponsiveness and stable asthma in the 6 weeks before enrollment, no current respiratory infection and not more than 2 lower respiratory infections requiring treatment in the past year. An additional criterion was worsening asthma control during a 2-week baseline test period during which time LABA were withheld. A total of 112 individuals met eligibility following the baseline test phase and were randomized to receive medical management with inhaled corticosteroids and long-acting beta-agonists (n=56) or the same medical management strategy plus bronchial thermoplasty 3 sessions approximately 3 weeks apart, (n=56). After follow-up visits at 3, 6 and 12 months, there was a 2-week period of abstinence from long-acting beta-agonists, during which time data on exacerbations were collected. Between data collection periods, patients could use all maintenance therapies. The primary outcome was the difference between groups in change in rate of mild exacerbations from the baseline 2-week abstinence period. An exacerbation was defined as the occurrence on 2 consecutive days of a reduction in the morning peak expiratory flow of at least 20% below the average value (recorded during the week before the abstinence period), the need for more than 3 additional puffs of rescue medication compared to the week before the abstinence period or nocturnal awakening caused by asthma symptoms. The study was powered to detect a difference between groups of 8 mild exacerbations per person per year. Data were available at 3-months for 100 of 112 patients (89%) and at 12 months for 101 patients (90%); all patients were included in the safety analysis. The mean number of mild exacerbations per person per week in the bronchial thermoplasty group was 0.35 during the baseline test period and 18 per person per week at 12 months (a decrease of 0.17 per person per week). In the control group, the mean number of mild exacerbations per person per week was 0.28 at baseline and 0.31 at 12 months (an increase of 0.03 per person per week). Compared to the control group, the bronchial thermoplasty group had a significantly greater reduction in mild exacerbations at the 12 month follow-up. Overall, the average number of exacerbations during the 2-week data collection periods at 3, 6 and 12 months decreased in the bronchial thermoplasty group, a mean decrease of 0.16 per person per week but not in the control group which had a mean increase of 0.04 mild exacerbations. This resulted in a mean difference of a mean of .20 mild exacerbations per week or about 10 per year. In contrast, there was not a significant difference between in the number of severe exacerbations at any time point, compared to baseline but the study may not have had sufficient statistical power for this outcome. At the 12-month follow-up, the mean number of severe exacerbations in the bronchial thermoplasty group was 0.01 per person per week compared to 0.07 at baseline. The number of severe exacerbations in the control group was 0.06 per person per week compared to 0.09 at baseline. The rate of adverse events was higher in the bronchial thermoplasty group during the active treatment period, but the proportion of adverse events was similar in the two groups in the post-treatment period. Post-treatment, 3 individuals in the bronchial thermoplasty group required hospitalization and 2 patients in the control group required a total of 3 hospitalizations. A limitation of the study is the lack of a sham intervention and consequently, an inability to blind patients to treatment group. Asthma Intervention Research 2 (AIR2) Trial: The AIR2 trial was conducted at 30 sites in 6 countries including the United States; findings were published in 2010 by Castro and colleagues (Castro, 2010). Unlike the other two 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 inhaled corticosteroids was required (equivalent to at least 1000ug 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 quality of life.) Also different from the AIR trial, patients were not required to experience symptom worsening during a period of abstinence from long-acting beta agonists. Patients were stable on their asthma medication and continued their medication regimen 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 endpoint, there the target was 96.4% to adjust for 2 interim looks at the data. The prior for the analysis was not reported in the article. In an unpublished FDA document reporting minutes from an advisory panel meeting, one of the study authors stated that they used a non-informative prior (Cox, 2007). A total of 297 individuals 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 and eight-five participants in the treatment group and ninety-seven in the sham control group attended the second bronchoscopy and the same numbers of individuals had the third bronchoscopy (it is not clear whether these were exactly the same patients). A total of 278 out of the 297 enrolled patients (94%) completed the 12-month visit, 181 in the treatment group and 97 in the sham control group. In the intention to treat population, the mean change in the integrated AQLQ score, the primary effectiveness outcome, was 1.35 in the bronchial thermoplasty group and 1.16 in the sham control group. Using Bayesian analysis, the posterior probability of superiority was 96%. This did not surpass the target PPS of 96.4%. However, in the ITT population, the percentage of patients achieving an AQLQ score change of 0.5 or greater (i.e., at least the minimal important difference) was 79% in the bronchial thermoplasty group and 64% in the control group. The posterior probability of superiority was 99.6% surpassed the target probability for secondary outcomes of 95%. Additional analysis of data from the active treatment group suggests 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 of 4.1 vs. 5.1, respectively). Several secondary outcomes favored bronchial thermoplasty over the sham control group. These include a reduction in the proportion of patients reporting asthma worsening during follow-up (27.3% vs. 42.9%, respectively, posterior probability of superiority 99.7%) and a reduction in the number of emergency room 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 to 0.70 per person per year in the control group (the PPS was 95.5%). There was no significant difference between groups in other secondary efficacy outcomes including morning peak expiratory flow, number of symptom-free days, symptom score and rescue medication use. Regarding safety outcomes, during the treatment phase, there was a higher rate of respiratory adverse events in the active treatment group (85% of participants mean of 1.0 events per bronchoscopy) compared to the sham group (76% of participants, mean of 0.7 events per bronchoscopy). A total of 16 patients (8.4%) in the active treatment group required 19 hospitalizations for respiratory symptoms during the treatment phase compared to 2 patients (2%) in the sham group who required 1 hospitalization each. However, during the post-treatment 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 study, 5 patients (2.6%) in the bronchial thermoplasty group had a total of 6 hospitalizations for respiratory symptoms and 4 patients (4.1%) in the sham group had 12 hospitalizations (1 patient had 9 hospitalizations). In the AIR2 study, the sham group had a relatively high rate of response e.g. 69% experienced a clinically significant increase in the AQLQ. Blinding appeared to be initially successful and remained so for the sham group. After the first bronchoscopy, 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. Long-term safety and effectiveness All 3 of the randomized controlled trials followed patients for 1 year. An unpublished FDA document reports some long-term follow-up data from extensions of the RISA and AIR trials. Fourteen of the 17 patients assigned to bronchial thermoplasty in the RISA trial have been followed through year 3, and follow-up will continue through year 5. Respiratory adverse events decreased from 8.4 per patient at year 1 to 0.9 at year 2 and 1.1 at year 3. Patients in the control group were not followed beyond 1 year. Seventy of the 112 (63%) patients from the AIR trial, 46 in the bronchial thermoplasty group and 24 controls, were followed through 3 years. During this time, the proportion of respiratory adverse events and the number of respiratory adverse events per person decreased in both groups and there were no significant differences between the groups. Continued follow up through 5 years (45 patients from the treatment group and 24 controls) revealed no difference in serious long-term adverse events (Thomson 2011). As part of the device approval process, the FDA has required a five-year post-approval study of the Alair bronchial thermoplasty device. Asthmatx will conduct the study which will include patients from the AIR2 trial as well as 300 additional patients. A search of the National Institutes of Health Clinicaltrials.gov database did not identify any additional trials evaluating bronchial thermoplasty that are planned or underway. Summary Three RCTs on bronchial thermoplasty have been published, including one double-blind sham-controlled study (AIR2). The high rate of response in the sham group of the AIR2 suggests a large placebo effect with novel asthma treatments, particularly for subjective outcomes such as quality of life; this calls into question conclusions about efficacy in the earlier trials that did not have a sham control. In the AIR2 trial, bronchial thermoplasty provided benefit in terms of quality of life and some, but not all, secondary outcomes. It is unclear, however, which patients are most likely to respond. Data from the AIR2 suggests that those with more severe asthma may experience the greatest improvement. Additional randomized trials using sham controls are needed to confirm the findings of the AIR2 study. In addition, long-term follow-up is needed to understand potential adverse complications. Technology Assessments, Guidelines and Position Statements National Heart, Lung and Blood Institute: Their most recent guidelines on the diagnosis and management of asthma, developed by an expert panel, were published in 2007 and did not mention bronchial thermoplasty. Hayes Medical Technology Directory gives a C rating to bronchial thermoplasty for severe, persistent asthma in patients who are age 18 years or older and whose asthma has not been well controlled by long-acting bronchodilators or glucocorticoids.
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Reference
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Castro M, Rubin AS, Laviolette M et al.(2010) 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. Centers for Disease Control and Prevention. Asthma fact sheet. Available on-line at http://cdc.gov/nchs/fastats/asthma.htm. Cox G, Thomson NC, Rubin AS et al.(2007) Asthma control during the year after bronchial thermoplasty. N Engl J Med 2007; 356(13):1327-37. FDA Executive Summary. PO80032 Alair Bronchial Thermoplasty System (Asthmatx Incorporated). Anesthesiology and Respiratory Therapy Devices Advisory Panel. October 28, 2009. Available online at 1Hhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/AnesthesiologyandRespiratoryTherapyDevicesPanel/UCM187825. pdf Food and Drug Administration News Release. April 27, 2010. Available online at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm209909.htm National Heart Lung and Blood Institute. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma (EPR-3). 2007. Available on-line at http://www.nhlbi.nih.gov/guidelines/asthma. Pavord ID, Cox G, Thomson NC et al.(2007) Safety and efficacy of bronchial thermoplasty in symptomatic severe asthma. Am J Respir Crit Care Med 2007; 176(12): 1185-91. Transcript. FDA Anesthesiology and Respiratory Therapy Devices Advisory Panel. October 28, 2009. Available online at 0Hhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/AnesthesiologyandRespiratoryTherapyDevicesPanel/UCM196567. Pdf Thomson NC et al. Long-term (5 year) safety of bronchial thermoplasty: Asthma intervention research (AIR) trial. BMC Pulm Med. 2011; 11:8. Hayes Technology Assessment (2012) Alair Bronchial Thermoplasty System for Treatment of Asthma. Published Dec 28 2012.
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Application to Products
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This policy applies to all health plans administered by QualChoice, both those insured by QualChoice and those that are self-funded by the sponsoring employer, unless there is indication in this policy otherwise or a stated exclusion in your medical plan booklet. Consult the individual plan sponsor Summary Plan Description (SPD) for self-insured plans or the specific Evidence of Coverage (EOC) for those plans insured by QualChoice. In the event of a discrepancy between this policy and a self-insured customer’s SPD or the specific QualChoice EOC, the SPD or EOC, as applicable, will prevail. State and federal mandates will be followed as they apply.
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Changes: QualChoice reserves the right to alter, amend, change or supplement benefit interpretations as needed.
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