(127) Use of Riluzole Beyond Approved Therapeutic Indications in Three Italian Regions

Saturday, August 27, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 801

Presenting Author(s)

Ursula Kirchmayer, MPH, FISPE
– MPH, FISPE, ASL Roma 1 Regione Lazio, Roma, Roma, Italy

Co-Author(s)

Marco Finocchietti
– Dipartimento di Epidemiologia del Servizio Sanitario Regionale della Regione Lazio, Roma, Roma, Italy
Niccolo' Lombardi, PharmD, PhD
– PharmD, PhD, Specialist Trainee in Clinical Pharmacology and Toxicology, University of Florence, Firenze, Italy
Giada Crescioli
– Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Italy, Italy
Emiliano Cappello
– Department of Clinical and Experimental Medicine, Unit of Pharmacology and Pharmacovigilance, University of Pisa, Pisa, Italy, Pisa, Toscana, Italy
Giulia Valdiserra
– Department of Clinical and Experimental Medicine, Unit of Pharmacology and Pharmacovigilance, University of Pisa, Pisa, Italy, Pisa, Toscana, Italy
Marco Tuccori
– Unit of Adverse Drug Reactions Monitoring, University Hospital of Pisa, Tuscan Regional Centre of Pharmacovigilance, Pisa, Italy; Department of Clinical and Experimental Medicine, Unit of Pharmacology and Pharmacovigilance, University of Pisa, Pisa, Italy, Pisa, Toscana, Italy
Alfredo Vannacci
– Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Italy, Italy
Olga Paoletti
– ARS Toscana, Florence, Italy, Italy
David Franchini
– Health ICT Service, Regional Health Authority of Umbria, Perugia, Italy, Italy
Marcello De Giorgi
– Health ICT Service, Regional Health Authority of Umbria, Perugia, Italy, Italy
Silvia Cascini
– Department of Epidemiology, ASL Roma 1, Lazio Regional Health Service, Rome, Italy, Italy
Anna Maria Bargagli
– Department of Epidemiology, ASL Roma 1, Lazio Regional Health Service, Rome, Italy, Italy
Teresa Anna Cantisani
– Neurophysiopathology, Perugia Hospital, Perugia, Italy, Italy
Maria Grazia Celani
– Neurophysiopathology, Perugia Hospital, Perugia, Italy, Italy
Paola Brunori
– Neurophysiopathology, Perugia Hospital, Perugia, Italy, Italy
Nicola Vanacore
– National Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, Italy, Italy
Francesco Sciancalepore
– National Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, Italy, Italy
Antonio Ancidoni
– National Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, Italy, Italy
Roberto Bonaiuti
– Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Italy, Italy
Giulia Hyeraci
– Agenzia Regionale di Sanit� Toscana, Firenze, Firenze, Italy
Rosa Gini, PhD
– Agenzia Reg Della Sanit, Firenze, Firenze, Italy
Giampaolo Bucaneve
– Regional Center of Pharmacovigilance, Health Authority of Umbria, Perugia, Italy, Italy
Rosalba Elisabetta Rocchi
– Regional Center of Pharmacovigilance, Health Authority of Umbria, Perugia, Italy, Italy
Mariangela Rossi
– Regional Center of Pharmacovigilance, Health Authority of Umbria, Perugia, Italy, Italy
Valeria Belleudi
– Statistician, Department of Epidemiology, ASL Roma 1, Lazio Regional Health Service, Rome, Italy, Roma, Italy
Antonio Addis
– Department of Epidemiology, ASL Roma 1, Lazio Regional Health Service, Rome, Italy, Italy

Background: Riluzole was the first disease-modifying drug authorized for the treatment of Amyotrophic Lateral Sclerosis (ALS) in Italy. Therapeutic indications for riluzole limit its use to patients without specific contraindications. Furthermore, the drug is not indicated for motor neuron diseases other than ALS (o-MND).

Objectives: Our first objective was to describe riluzole use in ALS patients with contraindications to its use and the second objective was to describe off-label riluzole use among patients with o-MND in the Italian regions of Lazio, Tuscany, and Umbria.

Methods: Objective 1: a cohort of adults prescribed riluzole for the first time (index date) during the years 2016-2019 and with a previously recorded ALS diagnosis was constructed using the regional administrative healthcare databases. Patients with o-MND recorded in the 5 years before the index date were excluded. Contraindications considered at index date were: being affected by ALS for more than 5 years, presence of tracheotomy, and renal or hepatic failure in the 5 years before the index date.
Objective 2: for the analysis of off-label use, a cohort of patients with o-MND diagnosis in 2016-2019 was enrolled and followed for up to 4 years on riluzole use. Prevalence of riluzole use was analyzed stratified by sex, Italian region, and over person time.

Results: Objective 1: the study population included 206 ALS patients prescribed riluzole in Lazio, 336 in Tuscany, and 60 in Umbria. Less than 1% had a recorded history of ALS of more than 5 years. Less than 2% had undergone tracheotomy or were affected by hepatic failure. Renal failure was documented for 1.9%, 2.7%, and 5.0% of ALS patients in Lazio, Tuscany, and Umbria, respectively. Objective 2: the o-MND cohort comprised 264 patients in Lazio, 222 in Tuscany, and 66 in Umbria. Off-label riluzole use was observed, with differences between regions and sexes. Prevalence of riluzole use were 8.5% in females, 19.9% in males in Lazio, 33.0% in females, 26.5% in males in Tuscany and 4.2% in females and 2.4% in males in Umbria. Prevalence of riluzole use was stable over time, except in Tuscany, where some fluctuation was registered, ranging between 17.9% and 34.4% for males and 26.7% and 50.0% for females.

Conclusions: Riluzole use in ALS patients in the presence of contraindications is rare in the 3 Italian regions, with slightly greater use in the presence of renal failure, especially in Umbria. Off-label riluzole use in o-MND was found to be non-negligible, with variations between sexes and regions. Our observations may be partially explained by the lack of specific disease modifying medications in o-MND, on differences between regional health policies.