Riluzole use in presence of contraindications in adults affected by amyotrophic lateral sclerosis and its off-label use in other motor neuron diseases: Findings from an Italian multicentre study (the CAESAR project) Giada Crescioli 1,2† , Marco Finocchietti 3† , Silvia Cascini 3 , Olga Paoletti 4 , David Franchini 5 , Emiliano Cappello 6 , Giulia Valdiserra 6 , Francesco Sciancalepore 7 , Maria Grazia Celani 8 , Marco Tuccori 6,9 , Alfredo Vannacci 1,2 , Niccolò Lombardi 1,2 * ‡ Ursula Kirchmayer 3‡ and on behalf of the CAESAR Study Group 1 Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy, 2 Tuscan Regional Centre of Pharmacovigilance, Florence, Italy, 3 Department of Epidemiology, Latium Regional Health Service, Rome, Italy, 4 Regional Health Agency of Tuscany, Pharmacoepidemiology Unit, Florence, Italy, 5 Health ICT Service, Regional Health Authority of Umbria, Perugia, Italy, 6 Department of Clinical and Experimental Medicine, Unit of Pharmacology and Pharmacovigilance, University of Pisa, Pisa, Italy, 7 National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, Rome, Italy, 8 Neurophysiopathology Unit, Perugia Hospital, Perugia, Italy, 9 Unit of Adverse Drug Reaction Monitoring, University Hospital of Pisa, Pisa, Italy Background: This analysis describes the use of riluzole in amyotrophic lateral sclerosis (ALS) individuals with contraindications and off-label use for subjects with other motor neuron diseases (o-MND) in the Italian regions of Latium, Tuscany and Umbria. Methods: A cohort of adults with ALS prescribed with riluzole during the years 2016–2019 was enrolled from administrative healthcare databases, excluding subjects with o-MND in the preceding 5 years. Being affected by ALS for more than 5 years, presence of tracheostomy, renal or hepatic failure were considered as contraindications to the use of riluzole. A cohort of adults with o-MND was enrolled in 2016–2019 for whom off-label use of riluzole was retrieved up to 4 years, analysing over the time differences related to sex. Results: Among 206 ALS individuals prescribed with riluzole in Latium, 336 in Tuscany and 60 in Umbria, less than 1% were diagnosed with ALS for more than 5 years. Less than 2% were tracheotomised or affected by hepatic failure. Renal failure was documented for 1.9%, 2.7%, and 5.0% of ALS individuals in Latium, OPEN ACCESS EDITED BY Jeff Guo, University of Cincinnati, United States REVIEWED BY Guillermo Alberto Keller, Universidad de Buenos Aires, Argentina Khaled Alamri, University of Cincinnati, United States *CORRESPONDENCE Niccolò Lombardi, niccolo.lombardi@unifi.it † These authors share first authorship ‡ These authors share last authorship SPECIALTY SECTION This article was submitted to Advanced Methods in Pharmacovigilance and Pharmacoepidemiology, a section of the journal Frontiers in Drug Safety and Regulation RECEIVED 10 September 2022 ACCEPTED 13 October 2022 PUBLISHED 25 October 2022 CITATION Crescioli G, Finocchietti M, Cascini S, Paoletti O, Franchini D, Cappello E, Valdiserra G, Sciancalepore F, Celani MG, Tuccori M, Vannacci A, Lombardi N and Kirchmayer U (2022), Riluzole use in presence of contraindications in adults affected by amyotrophic lateral sclerosis and its off- label use in other motor neuron diseases: Findings from an Italian multicentre study (the CAESAR project). Front. Drug. Saf. Regul. 2:1041275. doi: 10.3389/fdsfr.2022.1041275 COPYRIGHT © 2022 Crescioli, Finocchietti, Cascini, Paoletti, Franchini, Cappello, Valdiserra, Sciancalepore, Celani, Tuccori, Vannacci, Lombardi and Kirchmayer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Frontiers in Drug Safety and Regulation frontiersin.org 01 TYPE Brief Research Report PUBLISHED 25 October 2022 DOI 10.3389/fdsfr.2022.1041275