Researchers conducted a post-hoc analysis of Study 19 to determine hazard ratios of milestone occurrences in amyotrophic lateral sclerosis.
Data from a recent study suggest that early intervention with intravenous (IV) edaravone (Radicava; Mitsubishi Tanabe Pharma America) reduced death, tracheostomy, permanent assisted ventilation (PAV), and hospitalization in patients with amyotrophic lateral sclerosis (ALS).1
Findings from Study 19 (NCT01492686) were presented at the Muscular Dystrophy Association’s (MDA) Scientific and Clinical Conference 2021, March 15-18, by first author Benjamin Brooks, MD, medical director, Atrium Health Neurosciences Institute, Carolinas Medical Center.
“The lifespan for patients with ALS is around 3 to 5 years from the time of onset, and the mortality rate is 50% within 30 months of symptom onset. In edaravone pivotal Study 19 in ALS patients, IV edaravone was associated with significantly less functional decline compared with placebo,” Brooks and colleagues wrote.
Study 19 consisted of a 24-week double-blind period of edaravone versus placebo followed by a 24-week open-label period in which all patients received IV edaravone (edaravone-edaravone [EE] and placebo-edaravone [PE] patient groups). Brooks and colleagues conducted a post-hoc analysis of the study to assess the effects of IV edaravone and milestone effects in ALS. They conducted survival analyses of death, tracheostomy, PAV, and hospitalization due to ALS progression.
No deaths occurred during the double-blind period. During the open-label period, 2 deaths (2.9%) occurred in the EE group and 4 (5.9%) in the PE group. Hazard ratios for death were 0.48 (95% CI, 0.08-2.73; P = .4059) in the EE compared to the PE group.
Brooks and colleagues determined the HR for the cumulative occurrence of death, tracheostomy, or PAV to be 0.44 (95% CI, 0.10-1.81; P = .2523) in the EE group (n = 3; 4.3%) compared to the PE group (n = 6; 8.8%). Adding hospitalization to the cumulative survival analysis yielded a statistically significant HR of 0.47 (95% CI, 0.25-0.88; P = .0189) in the EE group (n = 20; 29.0%) compared to the PE group (n = 27; 39.7%).,
“The results of this analysis have not been replicated in a double-blind, placebo-controlled trial and no definitive conclusions can be drawn from these results without additional, appropriately controlled, clinical observational studies... Further research is recommended to confirm these findings,” Brooks and colleagues concluded.
In Study 19, researchers documented a least square mean change of –5.01 (standard error [SE], 0.64) from baseline in ALS Functional Rating Scale (ALSFRS-R) scores in the edaravone group compared with a change of –7.50 (SE, 0.66) in the placebo group. That 2.49-point difference (SE, 0.76 [95% CI, 0.99-3.98]; P = .0013) represented a 33% improvement in ALSFRS-R in patients with reduced forced vital capacity (FVC) of <80% prior to starting edaravone versus placebo.2
Last year, edaravone was also shown to be effective regardless of FVC in a post-hoc analysis conducted by Gary Pattee, MD, Neurology Associates, and colleagues, who aimed to evaluate the efficacy of edaravone in patients with bulbar-onset ALS and specifically those with FVC of either >80% or <80%.3
Through 48 weeks, patients in both the bulbar and limb-onset groups experienced a reduction in ALSFRS-R score loss versus placebo following treatment. Patients with bulbar-onset ALS with either >80% or <80% experienced similar ALSFRS-R scores, indicating the drug’s efficacy regardless of FVC.
For more coverage of MDA 2021, click here.