Non-Invasive Mechanical Ventilation reduces the Motor Decline in Amyotrophic Lateral Sclerosis

Background Non-invasive mechanical ventilation (NIMV) improves Amyotrophic Lateral Sclerosis (ALS) quality of life and survival. However, data about its effect on disease progression are still lacking. Objective To test whether NIMV use changed the rate of functional decline among ALS patients. Methods In this retrospective observational study, we included 465 ALS patients followed up at the ALS Center in Turin, Italy, who underwent NIMV during the disease course. The primary outcome was the change in functional decline after NIMV initiation when adjusting for covariates. Functional decline was based on the non-respiratory items of the ALS Functional Rating Score Revised (ALSFRS-R). Results A slower progression of functional decline followed NIMV initiation (mean improvement 0.13, 95%CI 0.11 to 0.16, p<0.001) regardless of sex, age at diagnosis, and disease duration prior to NIMV initiation. Indeed, the disease stage at NIMV initiation (early or advanced) did not influence the results. Respiratory support exerts its slowing effect mainly on the progression of spinal motor function. Conclusions We proved that NIMV influences the rate of motor progression in ALS. This result was not a consequence of the ALSFRS-R floor effect. The functional decline slowed after starting NIMV independently of the site of disease onset. Our results reinforce the importance of not delaying NIMV initiation in all ALS patients. NIMV-induced slowing of disease progression should also be accounted for when evaluating clinical trial outcomes. ### Competing Interest Statement ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Comitato Etico Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino (#355732). All participants gave informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data is available to interested researchers upon motivated and reasonable request.