IV Edaravone ALS Survival Study
(2022)Objective
To evaluate overall survival in US patients with ALS treated with intravenous edaravone compared with those not treated with IV edaravone in a real-world setting
Study Summary
• Risk of death was 27% lower in IV edaravone-treated patients (HR 0.73, p=0.005)
• Results support that beneficial treatment effects on functional decline may translate to increased survival
Intervention
Intravenous edaravone vs no IV edaravone treatment
Inclusion Criteria
Adults ≥18 years with ALS diagnosis (ICD-10-CM G12.21 or ICD-9-CM 335.20) enrolled in Optum Clinformatics Data Mart from 8 August 2017 to 31 March 2020
Study Design
Arms: IV edaravone-treated cases vs non-IV edaravone-treated matched controls
Patients per Arm: 318 per arm (636 total)
Outcome
• Median survival: 29.5 months (95% CI 25.4-35.9) vs 23.5 months (95% CI 20.0-28.0)
• HR 0.73 (95% CI 0.59-0.91; p=0.005)
Bottom Line
IV edaravone treatment was associated with a 6-month longer median survival and 27% lower risk of death compared with non-IV edaravone-treated patients in a predominantly riluzole-treated US cohort, though adequately powered RCTs are needed to confirm this finding.
Major Points
- This is the first study to show a statistically significant improved survival time associated with IV edaravone in ALS patients
- Median overall survival was 29.5 months with edaravone vs 23.5 months without (6-month difference)
- Risk of death was 27% lower in IV edaravone-treated cases (HR 0.73; 95% CI 0.59-0.91; p=0.005)
- 65.4% of patients in both groups had history of riluzole prescription
- Propensity score matching controlled for age, race, region, sex, insurance, cardiovascular disease, riluzole prescription, and disease severity surrogates
- Sensitivity analysis using inverse probability weighting confirmed findings (HR 0.65; 95% CI 0.53-0.79; p<0.0001)
- Median IV edaravone treatment duration was 8.6 months (IQR 3.5-14.8)
- Pre-index disease duration was approximately 7 months for both groups
Study Design
- Study Type
- Retrospective, observational, propensity score-matched comparative effectiveness cohort study
- Randomization
- No
- Blinding
- None (observational study)
- Sample Size
- 636
- Follow-up
- Until 31 March 2021 (median edaravone treatment 8.6 months; observation up to 31 months post-index)
- Countries
- United States
Primary Outcome
Definition: All-cause mortality confirmed via Optum De-identified CDM Database-Date of Death table (sourced from US Social Security Administration Death Master File and CMS claims)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 196 deaths (61.6%); Median survival 23.5 months (95% CI 20.0-28.0) | 155 deaths (48.7%); Median survival 29.5 months (95% CI 25.4-35.9) | 0.73 (0.59-0.91) | 0.005 |
Limitations & Criticisms
- Retrospective observational design limits causal inference; an adequately powered RCT is needed to confirm findings
- Administrative claims data subject to coding limitations and entry error
- Study included only patients with commercial health coverage or Medicare Advantage plans, limiting generalisability
- ALSFRS-R and FVC scores (clinical measures of disease severity) not available in claims database; surrogates used instead
- Possibility of underdiagnosis of ALS may have led to selection bias
- Adjustment limited to characteristics measurable from administrative claims; unmeasured confounding possible
- Cases and controls may have differential censoring patterns
- Index date for controls was the date edaravone became available (8 August 2017), not a treatment initiation date
- Patients who continued edaravone may have been inherently healthier (selection bias)
- Study population may appear healthier than total ALS population
- No information on ALS phenotype or site of onset
- Variable edaravone treatment duration among cases
Citation
eClinicalMedicine 2022;52:101590