Original Title: Efectividad de la ventilación mecánica no invasiva para el tratamiento de la insuficiencia respiratoria en pacientes con esclerosis lateral amiotrófica

Authors' objectives: To assess the effectiveness of non-invasive mechanical ventilation for the treatment of respiratory failure in patients with ALS.

Authors' results and conclusions: The present SR included a retrospective cohort study with prospective data collection of medium-high quality, two high and medium quality SR that assessed the effect of NIV on patients with ALS and a clinical practice guideline (CPG) that assessed the impact of NIV on the quality of life and survival of patients with motor neuron disease (MND). The review included a total of 1,759 adults with ALS. However, the best quality evidence came from one single RCT conducted on a sample of 41 patients with ALS. It should be noted that the conclusions reached by the two SR included in the report are mainly based on the above mentioned RCT. The RCT showed that NIV increased survival by 48 days in the treated group in comparison to the control group (CG) (219 vs. 171 days, p=0.006, estimated CI 95%: 12 to 91 days). The sub-group analysis indicated a large improvement in the median survival (205 days) in patients with good to moderate bulbar function treated with NIV (median of 216 days in the intervention group (IG) vs 11 days in the CG, p=0. 0059), but there was no noticeable increase in survival amongst patients with bulbar impairment. The cohort study (n=929) included in the SR indicated that in patients that used NIV survival increased by 13 months, almost by 40% (HR=0.61; CI 95%: 0.51 to 0.73) and the positive effect was maintained after adjusting the model for confounding factors. Unlike the RCT, the effect of NIV on patients with bulbar impairment in terms of survival was even greater, showing a significant increase in survival of 19 months (HR univariate=0.50; CI 95%: 0.36 to 0.70; HR multivariate = 0.59; CI 95%: 0.41 to 0.83). Patients that received NIV had large improvements in the duration that quality of life remained above 75% of baseline (TiMCS >75%: 168 days in the IG vs 99 days in the CG, p=0.0017 and Tisym >75%: 192 days vs 46 days, p=0.0013) and in the time weighted mean improvement inquality of life (μMCS 2.31 vs 0.00, p=0.0082 and μsym 1.07 vs 0.00, p less-than 0.0001). The benefits in the quality of life were even greater in the sub-group of patients without bulbar impairment. In patients with bulbar impairment, some of the indexes of quality of life in the SAQLI (daily functioning, social isolation and symptoms) and the dyspnoea domain of the CRQ showed an improvement. Low quality evidence derived from prospective studies with repeated measurements suggests that the main benefits of NIV were obtained for somnolence and fatigue perceived by patients. CONCLUSIONS The results from the only RCT available and from a cohort study of medium-high quality suggest that treatment with NIV has a major role in improving survival amongst patients with ALS. The magnitude of the effect on survival was noticeable for patients with little to moderate bulbar impairment according to the RCT. Despite the evidence drawn from the RCT indicating that NIV had no effect in terms of survival in patients with bulbar impairment, the cohort study with a large sample size suggested the opposite. The benefits of NIV on the quality of life were even greater than the benefits on survival, where the greatest improvements were obtained in the domains that evaluated sleep-related problems. Some quality of life indices showed an improvement in patients with severe bulbar impairment. The studies included in this SR provide high to moderate quality evidence in favour of equal access to NIV treatment for all patients with ALS with symptoms of nocturnal hypoventilation, even for those with severe bulbar impairment.

Authors' methods: A systematic review (SR) of the scientific literature was undertaken. The following databases were consulted: Medline (PubMed), Embase (OVID), Cochrane Library (Wiley) and The Centre for Reviews and Dissemination (CRD). The process was completed by launching searches on meta-search engines such as, TripDatabase and the Emergency Care Research Institute (ECRI Institute). The electronic searches were supplemented by manually scanning the reference lists from included articles to identify additional studies that may have been missed during the search of databases. Finally, The ClinicalTrials.gov database was examined to identify studies in progress or pending publication. Randomised controlled trials (RCT) (crossed or parallel), systematic reviews, meta-analyses, clinical practice guidelines and prospective and retrospective analytical observational studies (cohort studies) were selected. The methodological quality of the included studies was assessed with the FLC 2.0 software, developed by the Basque Office for Health Technology Assessment (Osteba). At the same time, the methodological quality of the non-randomised studies (cohort studies, quasi-randomised studies, etc.) was assessed using ACROBAT-NRSI (A Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies of Interventions). The methodological quality of the systematic reviews was assessed using the R-AMSTAR (Revised Assessment of Multiple Systematic Reviews). The level of evidence was classified following the method proposed by the Scottish Intercollegiate Guidelines Network (SIGN). Due to the high level of heterogeneity and the paucity of trials conducted in this research field, data were not meta-analysed.

Project Status: Completed

Year Published: 2017

URL for published report: https://www.ogasun.ejgv.euskadi.eus/r51-catpub/es/k75aWebPublicacionesWar/k75aObtenerPublicacionDigitalServlet?R01HNoPortal=true&N_LIBR=051936&N_EDIC=0001&C_IDIOM=es&FORMATO=.pdf

English language abstract: An English language summary is available

Publication Type: Rapid Review

Country: Spain

Organisation Name: Basque Office for Health Technology Assessment

Contact Address: C/ Donostia – San Sebastián, 1 (Edificio Lakua II, 4ª planta) 01010 Vitoria - Gasteiz

Contact Name: Lorea Galnares-Cordero

Contact Email: lgalnares@bioef.eus

Copyright: <p>Osteba (Basque Office for Health Technology Assessment) Health Department of the Basque Government</p>