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Edaravone efficacy in amyotrophic lateral sclerosis with reduced forced vital capacity: Post-hoc analysis of Study 19 (MCI186-19) [clinical trial NCT01492686]
Brooks, Benjamin Rix Heiman-Patterson, Terry Wiedau-Pazos, Martina Liu, Shawn Zhang, Jeffrey Apple, Stephen
Brooks, Benjamin Rix
Heiman-Patterson, Terry
Wiedau-Pazos, Martina
Liu, Shawn
Zhang, Jeffrey
Apple, Stephen
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Journal article
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2022-06-14
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Neurology
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http://dx.doi.org/10.1371/journal.pone.0258614
Abstract
Background: Edaravone slowed the rate of functional decline in subjects with amyotrophic lateral sclerosis (ALS) in phase 3 study MCI186-19 (Study 19). One of the Study 19 inclusion criteria was forced vital capacity (FVC) ≥80% of predicted (≥80%p). Therefore, the study provided no information on edaravone efficacy in subjects with FVC <80%p. In Study 19, 24-week, double-blind treatment was followed by open-label treatment where all subjects received edaravone. At 24 weeks, some subjects had FVC <80%p (FVC24 <80%p). This allowed for post-hoc assessment of the effects of edaravone in subgroups of subjects with FVC24 ≥80%p vs <80%p. Objective: To address the question of the efficacy of edaravone in ALS patients with FVC <80%p. Methods: Post-hoc analysis of Study 19 comparing edaravone efficacy at week 48 in subjects with FVC24 ≥80%p vs <80%p. Results: With edaravone treatment, subjects in both the FVC24 ≥80%p and the FVC24 <80%p subgroups experienced a reduction in ALS Functional Rating Scale-Revised (ALSFRS-R) score loss vs placebo subjects through week 48. For the FVC24 ≥80%p subgroup, the changes in ALSFRS-R scores from baseline to week 48 were −7.63 for edaravone-edaravone vs −9.69 for placebo-edaravone, a difference of 2.05 (P = .034; 95% CI: 0.16, 3.94). For the FVC24 <80%p subgroup, the changes in ALSFRS-R scores from baseline to week 48 were −10.26 for edaravone-edaravone vs −15.20 for placebo-edaravone, a difference of 4.94 (P = .0038; 95% CI: 1.64, 8.25). Linear regression analysis indicated that, in the FVC24 <80%p subgroup, there was a notable change in the slope of the ALSFRS-R score-vs-time graph after the start of edaravone treatment. Conclusion: ALS subjects in the Study 19 placebo arm had a slowing in disease progression, even when edaravone was added with an FVC of <80%p prior to starting edaravone. A randomized, placebo-controlled study is needed to validate these post-hoc findings.
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Brooks BR, Heiman-Patterson T, Wiedau-Pazos M, Liu S, Zhang J, Apple S (2022) Edaravone efficacy in amyotrophic lateral sclerosis with reduced forced vital capacity: Post-hoc analysis of Study 19 (MCI186-19) [clinical trial NCT01492686]. PLoS ONE 17(6): e0258614. https://doi.org/10.1371/journal.pone.0258614
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PLoS ONE, Vol. 17
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