Assessment of IV Edaravone Use in the Management of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder that results in progressive deterioration of motor neurons in the ventral horn of the spinal cord, which results in loss of voluntary muscle movements.¹ Eventually, typical daily tasks become difficult to perform, and as the disease progresses, the ability to eat and breathe is impaired.² Reports from 2015 show the annual incidence of ALS is 5 cases per 100,000 people, with the total number of cases reported at more than 16,000 in the United States.³ In clinical practice, disease progression is routinely assessed by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Typical decline is 1 point per month.⁴

Unfortunately, at this time, ALS care focuses on symptom management, including prevention of weight loss; implementation of communication strategies; and management of pain, constipation, excess secretions, cramping, and breathing. Despite copious research into treatment options, few exist. Riluzole is an oral medication administered twice daily and has been on the market since 1995.^5-7 Efficacy was demonstrated in a study showing statistically significant survival at 12 months compared with controls (74% vs 58%, respectively; P = .014).⁶ Since its approval, riluzole has become part of standard-of-care ALS management.

In 2017, the US Food and Drug Administration (FDA) approved edaravone, an IV medication that was found to slow the progression of ALS in some patients.^8-12 Oxidative stress caused by free radicals is hypothesized to increase the progression of ALS by motor neuron degradation.¹³ Edaravone works as a free radical and peroxynitrite scavenger and has been shown to eliminate lipid peroxides and hydroxyl radicals known to damage endothelial and neuronal cells.¹²

Given the mechanism of action of edaravone, it seemed to be a promising option to slow the progression of ALS. A 2019 systematic review analyzed 3 randomized studies with 367 patients and found a statistically significant difference in change in ALSFRS-R scores between patients treated with edaravone for 24 weeks compared with patients treated with the placebo (mean difference, 1.63; 95% CI, 0.26-3.00; P = .02).¹² Secondary endpoints evaluated included percent forced vital capacity (%FVC), grip strength, and pinch strength: All showing no significant difference when comparing IV edaravone with placebo.

A 2022 postmarketing study of 324 patients with ALS evaluated the safety and efficacy of long-term edaravone treatment. IV edaravone therapy for > 24 weeks was well tolerated, although it was not associated with any disease-modifying benefit when comparing ALSFRS-R scores with patients not receiving edaravone over a median 13.9 months (ALSFRS-R points/month, -0.91 vs -0.85; P = .37).¹³ A third ALS treatment medication, sodium phenylbutyrate/taurursodiol was approved in 2022 but not available during our study period and not included here.^14,15

Studies have shown an increased incidence of ALS in the veteran population. Veterans serving in the Gulf War were nearly twice as likely to develop ALS as those not serving in the Gulf.¹⁶ However, existing literature regarding the effectiveness of edaravone does not specifically examine the effect on this unique population. The objective of this study was to assess the effect of IV edaravone on ALS progression in veterans compared with veterans who received standard of care.