Effect of edaravone therapy in Korean amyotrophic lateral sclerosis (ALS) patients

Park, Jin‐Mo; Kim, Sun‐Young; Park, Donghwi; Park, Jin-Sung

doi:10.1007/s10072-019-04055-3

Cited by 34 publications

(37 citation statements)

References 16 publications

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“…Matching on additional factors may improve comparison, including ALS-FRS-R score components, ALS-onset type (bulbar vs nonbulbar), and pulmonary and muscular function. 10 Second, some outcomes were infrequently captured in VA databases (eg, ALS-FRS-R score and functional-status surrogate markers). Edaravone exposure was based on only the first and last prescription fill dates within the VHA, as we could not capture cycles received in non-VHA settings.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Assessment of Use and Safety of Edaravone for Amyotrophic Lateral Sclerosis in the Veterans Affairs Health Care System

Tortorice²,

Zacher³

et al. 2020

JAMA Netw Open

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IMPORTANCE 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. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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 (Ն6 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. EXPOSURES Edaravone (alone or with riluzole) vs riluzole only. MAIN OUTCOMES AND MEASURES 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. RESULTS 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.

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Section: Strengths and Limitationsmentioning

confidence: 99%

Assessment of Use and Safety of Edaravone for Amyotrophic Lateral Sclerosis in the Veterans Affairs Health Care System

Tortorice²,

Zacher³

et al. 2020

JAMA Netw Open

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“…Focusing on the involvement of oxidative stress in the pathogenesis of ALS, some therapeutic agents showing antioxidant effects have been developed [138]. The therapeutic efficacy of edaravone, a free radical scavenger, has been demonstrated in patients with ALS [139,140]. In addition, similar to Parkinson's disease, several therapeutic studies yielded positive outcomes of non-radioactive Cu-ATSM in SOD1-mutant mouse models of ALS, including improved locomotive function and overall survival [141,142].…”

Section: Oxidative Stress and Mitochondrial Dysfunction In Alsmentioning

confidence: 99%

PET Imaging for Oxidative Stress in Neurodegenerative Disorders Associated with Mitochondrial Dysfunction

et al. 2020

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Oxidative stress based on mitochondrial dysfunction is assumed to be the principal molecular mechanism for the pathogenesis of many neurodegenerative disorders. However, the effects of oxidative stress on the neurodegeneration process in living patients remain to be elucidated. Molecular imaging with positron emission tomography (PET) can directly evaluate subtle biological changes, including the redox status. The present review focuses on recent advances in PET imaging for oxidative stress, in particular the use of the Cu-ATSM radioligand, in neurodegenerative disorders associated with mitochondrial dysfunction. Since reactive oxygen species are mostly generated by leakage of excess electrons from an over-reductive state due to mitochondrial respiratory chain impairment, PET with 62Cu-ATSM, the accumulation of which depends on an over-reductive state, is able to image oxidative stress. 62Cu-ATSM PET studies demonstrated enhanced oxidative stress in the disease-related brain regions of patients with mitochondrial disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Furthermore, the magnitude of oxidative stress increased with disease severity, indicating that oxidative stress based on mitochondrial dysfunction contributes to promoting neurodegeneration in these diseases. Oxidative stress imaging has improved our insights into the pathological mechanisms of neurodegenerative disorders, and is a promising tool for monitoring further antioxidant therapies.

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“…Overall, there was a modest effect of edaravone on the Korean population. Minor side effects were reported in three patients, and 16% of patients reported severe adverse events [ 21 ]. No deaths were found during the Korean study.…”

Section: Reviewmentioning

confidence: 99%

“…No deaths were found during the Korean study. During the Korean study, the inclusion and exclusion criteria where edaravone was effective were not used [ 21 ].…”

Section: Reviewmentioning

confidence: 99%

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Post-Marketing Experience of Edaravone in Amyotrophic Lateral Sclerosis: A Clinical Perspective and Comparison With the Clinical Trials of the Drug

Ortíz

Khan

Salem

et al. 2020

Cureus

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Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease that affects the upper and lower motor neurons. Currently, the only treatment for ALS is riluzole, which only has a limited effect on increasing survival from 3 to 6 months. New therapies are needed in the clinical setting for ALS. We aim to compare and contrast the clinical trials of edaravone and the post-marketing experience of the drug during this study. For the method, a search strategy was made using PubMed with the search terms "Amyotrophic lateral sclerosis" (MeSH) and "Edaravone" (MeSH). For inclusion criteria, we used full papers, studies involving humans, and studies published in the English language. We exclude meta-analyses, literature reviews, systematic reviews, studies involving animals, and studies not published in English. After close examination, 20 papers were used for the discussion in this review. The clinical trials showed efficacy in patients in reducing the revised ALS functional rating scale (ALSFRS-R) in patients with early ALS with selective criteria. We documented edaravone's post-marketing experience in six countries: Kuwait, South Korea, Argentina, United States, Israel, and Italy. During the study we analyzed, the forced vital capacity (FVC) and ALSFRS-R scored, together with edaravone's safety in the clinical trials and post-marketing experience. Edaravone seems to be more effective in Asia, where the ALSFRS-R scores and the FVC decline were similar to the clinical trial results in Japan. Studies in Europe did not find the drug clinically useful. At the same time, studies in United States and Argentina were mainly descriptive, so more information is needed to evaluate the drug's efficacy in that part of the world. The drug was well-tolerated in all studies. In conclusion, more studies need to be done worldwide to carry out and clarify the effectiveness of edaravone in the clinical setting.

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Effect of edaravone therapy in Korean amyotrophic lateral sclerosis (ALS) patients

Cited by 34 publications

References 16 publications

Assessment of Use and Safety of Edaravone for Amyotrophic Lateral Sclerosis in the Veterans Affairs Health Care System

Assessment of Use and Safety of Edaravone for Amyotrophic Lateral Sclerosis in the Veterans Affairs Health Care System

PET Imaging for Oxidative Stress in Neurodegenerative Disorders Associated with Mitochondrial Dysfunction

Post-Marketing Experience of Edaravone in Amyotrophic Lateral Sclerosis: A Clinical Perspective and Comparison With the Clinical Trials of the Drug

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