Riassunto analitico
Importance: Oral tauroursodeoxycholic acid (TUDCA) is a drug currently tested in Amyotrophic Lateral Sclerosis (ALS). While results of phase 3 clinical trials on this treatment are awaited, TUDCA is easily administered and reachable for ALS patients.
Objective: To evaluate overall survival and safety profile in patients with ALS from Emilia Romagna Region (Italy) treated with TUDCA in a real-world setting.
Design: Multicenter, propensity score–matched cohort study. Propensity score matching was based on age at onset, sex, phenotype, diagnostic latency, ALSFRS-R at first visit, disease progression rate at first visit, BMI at diagnosis.
Setting: The study was conducted between January 2015 and February 2022 in Emilia Romagna Region where a population registry collects key clinical features from all specialized MND centers in the region since 2009, and where TUDCA has been prescribed, after approval from the regional rare diseases technical group, since 2015 by the same centers.
Participants: Of the 627 patients screened, 86 patients with ALS treated with TUDCA for at least three consecutive months were matched using propensity score analysis with 172 ALS patients receiving usual care. All patients were residents of Emilia Romagna Region and regularly followed till 1st February 2022.
Exposure: Oral TUDCA administration versus standard therapy.
Main Outcomes and Measures: primary study outcome was survival difference between TUDCA exposed and unexposed patients. Secondary outcomes were the rate of decline of ALSFRS-R from onset to last visit and frequency and time to supporting procedures.
Results: 86 patients assumed TUDCA; 64 were male (74.4%) and mean age was 58.2 years(SD 9.2). Median overall survival time was 49.6 months among TUDCA treated patients (95%CI, 41.7-93.5) and 36.2 months in controls (95%CI, 32.7-41.6), with a lower risk of death for higher dosage TUDCA-exposed patients (HR 0.56; 95% CI, 0.38−0.83; P=0.004). No significant differences were observed in terms of rate of ALSFRS-r decline or time to support procedures. TUDCA was well tolerated except for a minority of patients (n=7, 8.1%) who discontinued the drug.
Conclusions and relevance: This study showed that ALS patients treated with TUDCA have a survival benefit. Additional prospective studies are needed before widespread use in clinics.
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