TUDCA at higher daily dose seen to extend survival: ALS registry study
'Real-world' findings await Phase 3 trial results of treatment, part of Relyvrio
People with amyotrophic lateral sclerosis (ALS) who are treated daily with 1,000 mg or higher doses of tauroursodeoxycholic acid (TUDCA) tend to live longer than those given standard care alone, according to an analysis of registry data.
“In our ‘real-world’ study, patients who received TUDCA at the higher dose survived longer,” the researchers wrote.
“Since this was not a controlled study, we cannot rule out additional confounding factors,” the researchers noted. But “pending the results of ongoing [Phase 3 clinical trials], this study seems to confirm” TUDCA’s potential benefit to ALS patients, they added.
TUDCA thought to help to protect nerve cells in ALS patients
TUDCA is a bile acid salt normally made in the liver. As an oral therapy, it’s long been used to treat liver disease, and accumulating evidence suggest it also may have nerve-protecting effects that can be beneficial in ALS.
The European Commission is sponsoring the Phase 3 TUDCA-ALS (NCT03800524) clinical trial to evaluate the oral treatment’s efficacy, given on top of standard treatment with riluzole (sold as Rilutek, Exservan, and Tiglutik), in people with recent ALS. The trial is expected to conclude later this year.
TUDCA is part of Relyvrio, alongside sodium phenylbutyrate. Relyvrio is approved to treat ALS in the U.S. and in Canada, where it’s sold under the brand name Albrioza. Amylyx Pharmaceuticals, Relyvrio’s developer, is running a Phase 3 study called PHOENIX (NCT05021536) to confirm the treatment’s efficacy.
While these large studies are ongoing, it’s not possible to say definitively whether TUDCA has a beneficial effect in ALS. Nonetheless, in some parts of Italy, it’s been common practice since 2015 to prescribe it off label for certain people with ALS.
Scientists in Italy analyzed available data from 86 ALS patients treated with TUDCA, as well as data covering 172 patients not using it. The two groups were matched for factors like sex, age at onset, diagnostic delay, and measures of disease severity and progression at ALS diagnosis.
Among those given TUDCA, treatment on average was started about eight months after diagnosis, or slightly more than 1.5 years after the first appearance of ALS symptoms. The median duration of TUDCA treatment was about a year.
TUDCA doses varied markedly from person to person, the researchers noted, though patients given lower doses tended to be older, and more commonly had bulbar-onset ALS where the disease initially affects muscles around the throat and mouth.
Over a median follow-up of more than three years, roughly half of all the patients in the analysis died or required a tracheostomy to assist breathing.
Median survival longer in ALS patients given TUDCA at 1 g or higher doses
Analyses showed that patients given TUDCA at daily doses of at least 1,000 mg had longer median survival times (56.5 months) compared to patients given lower doses (29.7 months) or patients not treated with TUDCA (36.2 months).
“High-dose TUDCA treatment yielded superior results in terms of survival both versus controls and low-dose treatment,” the researchers wrote.
In analyses comparing high-dose TUDCA to no TUDCA, statistical models indicated that treatment reduced the risk of death or tracheostomy by 55%. Analyses comparing patients on TUDCA for at least a year with untreated patients also found treatment prolonged survival.
“In our retrospective propensity score matched study, we found that treatment with TUDCA was associated with reduced risk of death and/or tracheotomy over 50% in patients treated with daily doses [of at least] 1000 mg in comparison to controls,” the researchers wrote.
About 1 in 5 patients given TUDCA experienced side effects that required stopping treatment or reducing the dose. The most common was diarrhea; some patients also reported abdominal pain or rash. In two cases, TUDCA-related side effects were serious enough to necessitate medical attention, but they resolved after treatment was stopped in both cases.
“Our study showed that the safety profile of TUDCA, even with a longer treatment duration, was mainly characterized by gastrointestinal side effects reported in almost 20% of TUDCA-exposed patients. … Drug reduction was sufficient for most patients presenting with side effects, but 35% of them (corresponding to 7% of the entire treated cohort) judged these effects intolerable and discontinued the treatment,” the researchers wrote.
This analysis is limited by the use of real-world data, which often is messier than those of clinical trials with stringent enrollment and measurement criteria, the researchers noted. Findings from ongoing trials will be needed to conclusively determine the likely efficacy and safety of TUDCA in ALS.