Abstract
Using real-world data, the US Department of Veterans Affairs (VA) initiated a surveillance evaluation of edaravone after its approval for amyotrophic lateral sclerosis (ALS) in 2017. The use and safety of edaravone for patients with ALS in the VA health care system remain to be assessed. To describe a pharmacovigilance surveillance initiative with edaravone to monitor patient characteristics, utilization (edaravone cycles and riluzole use), and safety and to evaluate safety/effectiveness. This propensity score-matched cohort study used data on 369 patients with documented definite or probable ALS in the Veterans Health Administration (VHA) with at least 1 prescription for edaravone between August 1, 2017, and September 30, 2019. The analysis compared edaravone (alone or with riluzole) with riluzole only. For chronic users (≥6 months of drug), a time-to-event model evaluated ALS-related outcomes, with censoring at outcome, death, or end of evaluation. Patients with Parkinson disease, dementia, schizophrenia, or significant respiratory insufficiency per diagnosis codes within 2 years before prescription initiation were excluded. In overall matched cohorts, 223 patients treated with edaravone were 1:3 propensity score matched based on predefined confounders. For the chronic user subgroup analysis, 96 patients receiving edaravone and 424 patients receiving riluzole only were included. Edaravone (alone or with riluzole) vs riluzole only. Patient characteristics, ALS drug use, and mortality. Acute outcomes (within 6 months of index) included proportion and mean time to event for death, discontinuation, or all-cause hospitalization, and outcomes for chronic users (receiving >6 months of treatment) included hazard ratios of outcomes related to disease-state progression. Of 369 patients who received edaravone, most were older (mean [SD] age, 64.6 [11.3] years), male (346 [93.8%]), and White (261 [70.7%]). As of September 2019, 59.9% of edaravone patients had discontinued treatment; of those, 49.5% (108 of 218) received only 1 to 3 treatment cycles. Approximately 30% (110 patients) died. In a matched evaluation, significantly more acute all-cause hospitalization events occurred with edaravone (35.4% vs 22.0% for riluzole only); 72.6% of the edaravone cohort received edaravone with riluzole. Among chronic users, edaravone patients (70.8% edaravone with riluzole) had an increased hazard ratio of ALS-associated hospitalization (2.51; 95% CI, 1.18-8.16). The death rate was lower with edaravone but the difference was not statistically significant. Early edaravone discontinuation was common in the VA. Although outcomes favored use of riluzole only in the matched analysis, results should be interpreted with caution, as unmeasured bias in observational data is likely.
Highlights
Since 2005, the US Department of Veterans Affairs (VA) health care system has provided care for more than 4000 veteran patients with amyotrophic lateral sclerosis (ALS), one of the largest ALS patient populations in a US health care system
Significantly more acute all-cause hospitalization events occurred with edaravone (35.4% vs 22.0% for riluzole only); 72.6% of the edaravone cohort received edaravone with riluzole
Edaravone patients (70.8% edaravone with riluzole) had an increased hazard ratio of ALS-associated hospitalization (2.51; 95% CI, 1.18-8.16)
Summary
Within the Veterans Health Administration (VHA), ALS is a presumptive service connection (eg, subsequent ALS diagnosis is related to veteran’s prior military service), with automatic qualification for VA benefits, including prescription coverage.. Pharmacotherapy has been limited, with only 2 treatments approved for ALS by the US Food and Drug Administration (FDA).. Riluzole was shown to significantly increase survival at 12 and 21 months in a randomized placebo-controlled trial; median survival was improved by only approximately 100 days (532 days for riluzole; 449 days for placebo).. Riluzole was shown to significantly increase survival at 12 and 21 months in a randomized placebo-controlled trial; median survival was improved by only approximately 100 days (532 days for riluzole; 449 days for placebo).6 This benefit was not observed in patients aged 75 years and older or those with advanced ALS.. Within the Veterans Health Administration (VHA), ALS is a presumptive service connection (eg, subsequent ALS diagnosis is related to veteran’s prior military service), with automatic qualification for VA benefits, including prescription coverage. Pharmacotherapy has been limited, with only 2 treatments approved for ALS by the US Food and Drug Administration (FDA). Edaravone was approved by the FDA in May 2017.4 Prior to edaravone approval, riluzole was the only FDA-approved treatment. Riluzole was shown to significantly increase survival at 12 and 21 months in a randomized placebo-controlled trial; median survival was improved by only approximately 100 days (532 days for riluzole; 449 days for placebo). this benefit was not observed in patients aged 75 years and older or those with advanced ALS. Survival was not assessed in the edaravone clinical trial.
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