Original Title: Termoplastia bronquial en asma persistente grave

Authors' objectives: To evaluate the safety and effectiveness of the bronchial thermoplasty technique in the short and long term in adult patients with severe persistent asthma who do not respond to the usual treatment (triple inhaled therapy and additional phenotype-targeted treatment).

Authors' results and conclusions: The literature search retrieved 14 HTA reports and 77 systematic reviews. One HTA document conducted by NICE in 2018 was selected and updated. The update provided 98 original studies, of which 9 met the selection criteria and were included in this review. In addition, 67 clinical practice guidelines (CPGs) and other expert consensus documents were located, including 5 CPGs and 4 position statements as additional evidence. The NICE document included 779 adult patients with moderate-severe asthma from 13 studies: 2 systematic reviews with meta-analyses [one with 12-month outcomes and meta-analyses of 3 RCTs (AIR, RISA and AIR2) and one with 5-year follow-up and meta-analyses of 6 studies (the above 3 RCTs and three 5-year extensions of the intervention arm (BT) series of the same RCTs]; 1 RCT with 5-year outcomes of AIR; 3 case series 5-year extensions of AIR2; 1 comparative study; 1 registry; 1 case series and 5 single-case studies to assess safety. The 9 primary studies from the NICE update consisted of 2 non-randomised comparative studies, 2 registries and 5 observational studies. Most were conducted in Europe and Australia and the methodological quality was moderate-high (low risk of bias according to the Robins-I scale and 15-16 scores on the IHE scale). They included 872 adult patients, 769 treated with BT and 103 controls; only one had longterm follow-up (>10 years) and the rest ranged from 1 to 2 years. One hundred and thirty one missed cases were recorded and the Alair BT system was used in all cases. Five clinical practice guidelines were included published between 2019 and 2020. All of them were consistent, of good methodological quality and issued recommendations based on a low quality of evidence level (level B) due to the limited evidence available and the uncertainties on the estimation of the effect. They consider that BT could be an alternative for the treatment of adult patients with severe asthma that persists poorly controlled despite optimized triple drug therapy (AGNC). That is, it includes patients with severe asthma who do not respond to additional therapy with macrolides (asthma associated with non-T2 phenotype), or who have not obtained a good response to biological therapy (anti-IgE, anti-IL5, anti- IL4 monoclonal antibodies) for the T2 phenotype). They recommend that the procedure be performed in highly experienced centres and suggest limiting its use in the context of a registry or research study, highlight the complexity and uncertainties in patient selection and the importance of improving selection criteria, specific staff training, the learning curve, the multidisciplinary approach and the need for further research on the long-term risk-benefit balance, among others. In terms of efficacy, the variables analysed were asthma control including symptom control, frequency of severe exacerbations and changes in lung function, and quality of life. Effectiveness data were derived from short-term follow-up of 329 patients included in 6 observational studies without a comparison group and from medium- and long-term follow-up (5-10 years) of patients included in PAS2 study (n=279) and of a subgroup of patients enrolled in the AIR, RISA and AIR-2 trials (n=192). Overall, the data analysed indicate that both BT-treated patients and controls improve symptom control, with the improvement being minimally relevant from the clinical point of view, although the difference between the two was not significant. Compared to conventional treatment, BT reduces to a greater extent the proportion of severe exacerbations whose effect seems to be sustained in the long term, shows similar efficacy in terms of reduction in the number of severe exacerbations and does not produce significant changes in lung function (FEV1 pre- or post-bronchodilator). In terms of quality of life, BT is associated with statistically significant, but not clinically relevant improvements and with a greater reduction in the number of days of absenteeism from work and/or school. In terms of safety, the most frequent adverse effects were airway irritation, worsening of asthma and lower respiratory tract infection, most of them mild, occurring the day after the BT session and resolving within one week. In the short term evolution, BT was associated with higher frequency of serious respiratory events that required hospitalization or emergency visits, but these differences disappeared over the time (12 months). During the treatment phase (first 3 months), BT was associated with a higher frequency of severe respiratory effects, higher risk of hospitalisation and longer hospital stay compared to conventional treatment. At the end of the first year these differences disappeared and reductions in the risk of hospitalisation and emergency room visits were observed in both groups. In the medium term (1-5 years) and long term (5-10 years), the frequency of respiratory events, emergency room visits and hospitalisation for respiratory events remain constant. Conclussions: - The BT procedure has an acceptable safety and effectiveness profile, although uncertainties remain about the estimation of effect and the need to improve patient selection criteria, which is key to its use. - Overall, the risk of adverse events associated with BT is greater during the first weeks after the intervention and the benefit is observed months later and remains constant over time (between 5 and 10 years). - In the short term evolution, TB is associated with a higher frequency of respiratory events requiring hospitalization or emergency visits, although these differences disappear over time. Most of the complications are of a moderate nature, occur during the treatment phase and disappear within a few days. At the end of the first year, a reduction in hospital admissions and emergency visits was observed, which remained constant in the medium and long term follow up. BT shows similar effectiveness to conventional treatment in terms of symptom control (minimally important clinical improvement), REDUCTION in the number of exacerbations per patient and quality of life (no significant differences or clinical relevance), and does not produce any significant change in lung function. - It is recommended that this procedure be performed in centres with severe asthma units, specialised in the management of patients with severe asthma and by professionals with extensive experience in specifically trained bronchoscopy procedures, only in patients with uncontrolled severe asthma phenotype not requiring treatment with biologic drugs (monoclonal antibodies) or in which these have failed. - Prior education and training is required, as well as a learning curve.

Authors' methods: A systematic review of the scientific literature was carried out without time restriction until June 2022, in databases specialised in HTA reports, systematic reviews and clinical practice guidelines (Centre for Reviews and Dissemination (CRD) Databases: Health Technology Assessment, HTA; International HTA database, Cochrane Library, POP database (EUnetHTA), NICE, CATDH, KCE, SIGN y Tripdatabase), general databases [Medline, EMBASE, Cochrane Library (CENTRAL)] and research projects underway (ClinicalTrials.gov and EU Clinical Trials Registry). A specific search strategy was designed using Mesh terms and different combinations of free terms and monthly updates of these searches. To complete the process and locate other relevant information, specific searches were conducted in meta-search engines and websites of national and international scientific societies and organisations, as well as a manual search based on a review of the literature cited in the included studies. The selection of studies was performed by independent, blinded peer review, according to the inclusion and exclusion criteria previously established in the study protocol. Data extraction from the studies that met the inclusion criteria was performed following a systematic methodology, with the data being entered into predefined evidence tables specifically designed to cover the relevant aspects of the studies. The synthesis of the evidence was done in a narrative form with tabulation of results.

Project Status: Completed

URL for project: https://runa.sergas.gal/xmlui/bitstream/handle/20.500.11940/17101/CT202102_Termoplastia_Bronquial.pdf?sequence=1&isAllowed=y

Year Published: 2022

URL for published report: https://runa.sergas.gal/xmlui/bitstream/handle/20.500.11940/17101/CT202102_Termoplastia_Bronquial.pdf?sequence=1&isAllowed=y

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Scientific Advice Unit, avalia-t; The Galician Health Knowledge Agency (ACIS)

Contact Address: Conselleria de Sanidade, Xunta de Galicia, San Lazaro s/n 15781 Santiago de Compostela, Spain. Tel: 34 981 541831; Fax: 34 981 542854;

Contact Name: avalia-t@sergas.es

Contact Email: avalia-t@sergas.es

Copyright: Galician Agency for Health Technology Assessment (AVALIA-T)