Long-term use of IV edaravone shows no significant slowing of ALS progression

The long-term use of IV edaravone in patients with ALS, although tolerated, did not produce significant improvement compared with standard therapies alone, according to a study published in JAMA Neurology.

“Our study indicated that edaravone in its current dosage and administration may not prolong time to ventilation or survival probability,” Simon Witzel, MD, of the department of neurology at Ulm University in Germany, and colleagues wrote. “Supported by real-world studies, our results raise doubts whether patients with ALS benefit from long-term intravenous edaravone treatment.”

Witzel and colleagues conducted a multicenter, propensity score-matched cohort study between June 2017 and March 2020 at 12 academic ALS referral centers associated with the German Motor Neuron Disease Network. After screening 1,440 patients, researchers analyzed 324 patients with ALS, including 194 who began IV edaravone treatment plus standard ALS therapy using riluzole and 130 matched patients who received only riluzole.

Investigators assessed the efficacy of edaravone treatment among patients who received at least four cycles, compared with propensity score-matched patients with ALS who received only riluzole. The primary outcome was disease progression measured by decrease in the ALS Functional Rating Scale–Revised (ALSFRS-R) score, and secondary outcomes were probability of survival, time to ventilation and change in disease progression before vs. during treatment.

Investigators observed potential adverse effects in only 30 cases, the most notable issues being infections at infusion sites and allergic reactions.

According to study results, there was no significant difference between disease progression in 116 patients treated with edaravone over a mean period of 13.9 months compared with 116 patients given only the standard treatment for a median of 11.2 months (ALSFRS-R points/month, 0.91 [95% CI, 0.69 to 1.07] vs. 0.85 [95% CI, 0.66 to 0.99]; P = .37).

“Our results raise doubts whether patients with ALS benefit from long-term intravenous edaravone treatment,” Witzel and colleagues wrote. “This doubt is particularly important in light of the time-consuming and challenging intravenous application.”

In an editorial, Jonathan D. Glass, MD and Christina N. Fournier, MD, MS, of the department of neurology at Emory University in Atlanta, praised the rigor of the German study and acknowledged the new data can contribute to ongoing conversations regarding edaravone’s potential as an alternative or adjuvant therapy.

However, the authors expressed concerns about marketing edaravone as a viable solution, considering its lack of trial data, cost and time-consuming treatment process. They reasoned that further rigorous study, leading to eventual FDA clearance, will only bolster the case for new treatments.

“The desperate search for new ALS therapies and the desire to bring new drugs to market are understandable,” Glass and Fournier wrote. “Our lack of effective therapies for ALS and other devastating neurodegenerative diseases reflects a lack of a clear understanding of underlying biological mechanisms and true druggable targets.”