(307) Efficacy and safety of riluzole in the treatment of Amyotrophic Lateral Sclerosis, a population based study in Italy

Background: Amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. It is a progressive disease, which leads to paralysis and death. Riluzole is a drug indicated to improve survival and time free from invasive mechanical ventilation, and is the only disease-modifying agent authorized in Italy for specific ALS therapy.

Objectives: In the context of a multicenter study on neurodegenerative diseases based on administrative healthcare data (Caesar project funded by the Italian Medicines Agency) we analyzed the efficacy and safety in riluzole users during the first year of use compared to non-users in the three Italian regions of Lazio, Umbria and Tuscany.

Methods: A retrospective cohort study was conducted by enrolling patients newly affected by ALS from hospital discharge records, emergency room visits and disease specific co-payment exemptions. We excluded patients under 18 years, not enrolled in the regional healthcare system and those who died within 30 days after enrollment. Each subject was followed from the date of first riluzole claim (index date) until interruption of treatment, occurrence of one of the outcomes under study (mortality, respiratory failure, percutaneous endoscopic gastrostomy (PEG), tracheostomy), death or alternatively end of the study (365 days from the index date). Riluzole consumption was modelled through Defined Daily Doses. Region specific Cox regression models adjusted for sociodemographic characteristics, disease-specific comorbidities, Charlson index and drug use in the two years preceding the index date were applied, estimating Hazard Ratios and related 95% confidence intervals, followed by metanalysis for mortality.

Results: Overall, 765 ALS patients were enrolled, of whom 58% in Lazio, 76% in Umbria and 83% in Tuscany region were riluzole users. Descriptive analysis showed that non-users had a higher frequency of specific comorbidities and anticoagulant use. Comparative analyses yielded point estimates in favor of riluzole for mortality (metanalysis: HR=0.77, 95%CI: 0.40-1.14) and tracheostomy in Lazio (HR=0.46, 95%CI: 0.17-1.25) without reaching statistical significance, whereas numbers were too small in Umbria and Tuscany. Results for respiratory failure were heterogeneous across regions with HRs varying between 0.68 (Umbria) and 3.13 (Tuscany). Riluzole use was associated with a higher risk of undergoing PEG.

Conclusions: Overall, the efficacy and safety profile of riluzole in our study was in line with clinical trials, even if results were not statically significant due to small numbers. Moreover, comparing users with non-users may have produced estimates affected by residual confounding.