Real-world Radicava use in ALS tied to unexpected side effects: Data
FDA reporting system shows therapy may cause liver problems, blood clots
The real-world use of Radicava (edaravone), an infusion treatment approved for amyotrophic lateral sclerosis (ALS), may cause serious side effects — such as liver problems, blood clots, pain, brain bleeding, and infection — not previously listed in its label, according to data from the U.S. drug regulatory agency’s adverse event reporting system.
These findings, culled from U.S. Food and Drug Administration (FDA) reporting information, provide useful insights for doctors and patients, per the researchers. However, the team noted that reporting on a treatment’s safety after it’s been put on the market is voluntary, so further research is needed to confirm these unexpected side effects and understand how often they occur in real-world use.
More evidence could help in “better guiding clinical practice and public health decision-making,” the researchers wrote.
The study, “Adverse events reporting of edaravone: a real-world analysis from FAERS database,” was published in the journal Scientific Reports.
ALS occurs due to the gradual loss of motor neurons, the nerve cells that control the body’s voluntary movements. The exact causes of ALS are unknown and may involve a combination of mechanisms. However, there is evidence that toxic molecules containing oxygen may damage motor neurons over time.
Radicava acts as an antioxidant, scavenging for oxygen-containing molecules that may damage nerve cells. By removing these toxic molecules, it’s expected to prevent the loss of motor neurons and slow disease progression. It was first approved for ALS as an intravenous, or into-the-vein, infusion, and is now also available as an oral suspension under the brand name Radicava ORS.
Team used FDA database to look at Radicava use in ALS in real world
Radicava’s safety profile was extensively assessed in clinical trials. The FDA, however, continues to gather safety data from drugs after they are marketed for patient use.
The agency’s adverse event reporting system, dubbed FAERS, is a database that allows patients and clinicians to report any safety issues related to a medication’s use in real-world settings.
To better understand Radicava’s side effects in such settings, a team of researchers in China looked at FAERS data collected from when the treatment was approved in the U.S., in 2017, through early 2024. Over that period, nearly 3,000 total reports of side effects to Radicava were added to the database, the researchers found.
“We gathered and used a large sample of real-world data from FEARS to evaluate the safety of [Radicava] through pharmacovigilance,” the team wrote. Pharmacovigilance refers to monitoring of a medication’s safety after approval.
“The purpose is to offer a resource for clinical practice on pharmaceutical safety,” the team added.
This study extracted data between April 2017 and March 2024, and edaravone was identified as the ‘primary suspect (PS)’ in 2,986 [adverse events] reports. … [An analysis] revealed some unexpected potential [side effects].
Overall, more men than women (59.3% vs. 40.7%) reported side effects, and most reports came from patients or caregivers themselves (63.7%) rather than medical experts.
“In the FAERS database, this study extracted data between April 2017 and March 2024, and edaravone was identified as the ‘primary suspect (PS)’ in 2,986 [adverse events] reports,” the team wrote.
The majority of individuals who experienced side effects related to Radicava were also on other medications, which could have contributed to the side effects, the researchers noted. One such medication was riluzole, another ALS treatment marketed as Rilutek and used by 57.1% of these patients. A total of 13.3% of patients were taking phenylbutyrate, and about 8% were taking the muscle relaxant baclofen or anti-inflammatory aspirin. Gabapentin, an antiseizure medication, was used by about 5% of patients experiencing side effects.
Unexpected side effects ranged from pain to brain bleeding
The U.S. had the highest number of reports, at 84%. A total of 9% of reports were from Japan, with 1% from China. The therapy is approved for use in ALS in Canada, but not in most European nations.
The most serious outcome was death, followed by hospitalization, life-threatening complications, and disability, per the researchers.
Weakness, difficulty walking, unexpected treatment response, respiratory failure, and difficulty breathing were the side effects most commonly reported with Radicava use. The most serious included blood clots in the intravenous line (catheter), abnormal openings in the stomach (fistulas), swelling or infection around the catheter, and collapsed vein.
Some unexpected but significant side effects, which aren’t listed in Radicava’s label, included liver problems, blood clots, pain, brain bleeding, infection, stroke, difficulty accessing the vein, and damage to the vein used for infusion.
After removing incomplete data, 303 cases (10.2%) recorded the time when side effects began, with a median time of onset of 16 days after starting treatment. Most side effects (56.1%) occurred within the first month, with fewer cases being reported after two months (7.6%) and three months (10.2%), the data showed.
According to the researchers, this analysis “revealed some unexpected potential [side effects] that can direct future clinical investigations, despite the unavoidable limitations of the FAERS database employed in pharmacovigilance studies.” The team suggested further investigation.
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