Milestone-Free Time Longer in IV Edaravone-Treated Patients With ALS, Administrative Claims Suggest

James Berry, MD, MPH

Findings from a real-world analysis of administrative claims of patients with amyotrophic lateral sclerosis (ALS) showed that those treated with intravenous (IV) edaravone (Radicava; MT Pharma) demonstrated longer milestone-free time and had fewer reported deaths than patients with ALS not treated with the agent.

Led by James Berry, MD, MPH, director, Massachusetts General Hospital ALS Care Center, the study included 360 IV edaravone-treated patients with ALS and 360 non-IV edaravone-treated patients with ALS who were matched on several covariates. Presented at the 2023 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 19-22, in Dallas, Texas, the study included milestones of canes/walkers/wheelchairs (M1), artificial nutrition (M2), noninvasive ventilation (M3), invasive ventilation (M4), speech-generating devices (M5), and hospice (M6).

Cases and controls had similar mean ages, and were matched on other covariates such as race, geographic region, gender, pre-index disease duration, insurance, cardiovascular disease history, riluzole prescription, gastrostomy tube placement, artificial nutrition, non-invasive ventilation, and all-cause hospitalization. Median treatment duration in the IV edaravone-treated group was 9.11 (IQR, 3.45-16.08) months. At baseline, the proportion of claims for bulbar-, limb-, nerve-, and respiratory-related symptoms were similar between the groups.

The data, pulled from 2017 to 2021, showed that more IV edaravone-treated cases reported an absence of milestones than non-IV edaravone-treated controls from 0-12 months after the index date. Additionally, fewer deaths occurred in the IV edaravone group than controls from 0-12 months and 12-24 months after the index date. Combined with data from the pivotal phase 3 trial, Study 19 (NCT01492686), which showed that treatment with edaravone slowed loss of physical function by 33%, these results provide an example of real-world impact of the medication, the study authors concluded.

Differences between the 2 groups in cause-specific restricted mean time lost (RMTL) was estimated to examine the benefit of IV edaravone while considering mortality as the competing risk. In the post-index period, differences in RMTL in months indicated longer milestone-free time in cases than controls (M1: 2.50 [IQR, 0.93-4.07]; M2: 4.30 [IQR, 2.88-5.72]; M3: 2.92 [IQR, 1.56-4.28]; M4: 0.92 [IQR, 0.25-1.58]; M5: 3.37 [IQR, 2.27-4.46]; M6: 2.33 [IQR, 1.31-3.34]). For the majority of reported milestones, IV edaravone-treated cases had longer milestone-free time than non-IV treated controls for both commercial and Medicare Advantage insurance.

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There were a few notable limitations to the study, including the fact that the analysis was limited to patients with commercial health coverage or Medicare Advantage plans. Additionally, while differences between cohorts were controlled by propensity score matching, adjustment was limited to those characteristics that can be measured from administrative claims. The study also excluded those no longer enrolled in the database during the post-index period, which may have made the study population appear healthier than the total population of patients with ALS in the database.

The original IV formulation of edaravone was FDA-approved in 2017 and is administered in 28-day cycles, with each patient receiving a 60 mg dose over the course of a 60-minute infusion. The oral formulation, which gained approval in 2022, requires a 14-day induction period of daily administration followed by a 2-week drug-free period. This initial cycle is followed by a 10-day treatment cycle every 14 days, which is followed by a 14-day drug-free period.²

Evidence from the phase 3 study assessing the IV formulation of the drug led to the approval of the oral formulation. The study featured 137 patients with ALS who were evaluated on changes of ALS Functional Rating Scale-Revised scores over a 24-week treatment period. An ongoing phase 3 study (NCT04577404) is also examining the long-term safety and tolerability of oral edaravone over 96 weeks.

REFERENCES
1. Ciepielewska M, Berry J, Hagan M, Zhang J, Liu Y. Longer milestone-free time to IV edaravone-treated vs IV edaravone-naïve amyotrophic lateral sclerosis patients: an administrative claims analysis. Presented at: 2023 MDA Clinical and Scientific Conference; March 19-22; Abstract 174.
2. Mitsubishi Tanabe Pharma America Announces FDA Approval of RADICAVA ORS® (edaravone) for the Treatment of ALS. News release. Mitsubishi Tanabe Pharma America. May 13, 2022. Accessed March 27, 2023. https://www.prnewswire.com/news-releases/mitsubishi-tanabe-pharma-america-announces-fda-approval-of-radicava-ors-edaravone-for-the-treatment-of-als-301546937.html