Dataset Information

Edaravone efficacy in amyotrophic lateral sclerosis with reduced forced vital capacity: Post-hoc analysis of Study 19 (MCI186-19) [clinical trial NCT01492686].

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.

SUBMITTER: Brooks BR

PROVIDER: S-EPMC9197041 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

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 BR Heiman-Patterson Terry T Wiedau-Pazos Martina M Liu Shawn S Zhang Jeffrey J Apple Stephen S

PloS one 20220614 6

<h4>Background</h4>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 ...[more]

PMID: 35700157

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Project description:RationaleBlack Africans have reduced FVC compared with white persons, but the prevalence and determinants of reduced values are not well understood.ObjectivesTo evaluate the prevalence and factors leading to reduced FVC in a Nigerian population and to examine current theories regarding the determinants of this difference.MethodsWe studied the ventilatory function of 883 adults aged 40 years or older participating in the Burden of Obstructive Lung Disease Study in Ile-Ife, Nigeria. Respondents completed pre- and post-bronchodilator spirometry test and provided information on their smoking history, respiratory symptoms, risk factors, and diagnoses, including anthropometric details. We used standard categories to define body mass index as either underweight, normal, overweight, or obese. We defined reduced FVC as a post-bronchodilator FVC below the lower limit of normal using National Health and Nutrition Examination Survey (NHANES) equations, Global Lung Function Initiative 2012 equations, and local reference equations based on nonsmoking study participants without a respiratory diagnosis. We fit multivariate linear regression models to FVC as a continuous measure, adjusting for age, sex, height, and other confounders.ResultsThe prevalence of reduced FVC was 70.4% for men and 72.8% for women when using NHANES values for white Americans, 17.8% for men and 14.4% for women using NHANES equations for African Americans, and 15.5% for men and 20.5% for women using the Global Lung Function Initiative 2012 equations. Using the equations derived from nonsmoking respondents in the survey without a respiratory diagnosis, the prevalence of reduced FVC was less than 4% for both men and women. FVC was lower in participants who had less than 7 years of education (FVC, -96 ml; 95% confidence interval [CI], -172 to -19), were underweight (FVC, -269 ml; 95% CI, -464 to -73), were overweight (FVC, -132 ml; 95% CI, -219 to -46), and were obese (FVC, -222 ml; 95% CI, -332 to -112).ConclusionsThere is a wide variation in the prevalence of reduced FVC based on the reference standard used. This variation is not satisfactorily explained by factors thought to affect FVC within individual populations. However, the prevalence strongly associates with both education level and body mass index in this population, regardless of the specific standard used.

Project description:Purpose: Poor forced vital capacity (FVC) effort has been considered to be the main reason for FVC reduction by the ATS/ERS guideline; however, this has rarely been mentioned in previous studies. The present study aims to determine whether reduced FVC in asthmatic children is correlated to poor FVC effort. Methods: A total of 209 asthmatic children within 5-13 years old were included and divided into reduced FVC ("restricted," n = 66) and typical obstruction group ("obstructed," n = 143). Forced expiratory flows before and after bronchodilation were recorded in asthmatic children. The differences in clinical characteristics, spirometric results, FVC effort, and bronchodilator response were compared between two groups. Exhalation time (ET) was divided into effective ET (ETe) and plateau ET (ETp) by the start point of exhalation plateau on the time-volume curve. FVC effort was assessed by ET, ETp, and back extrapolated volume (EV)/FVC (%). Results: Asthmatic children in the restricted group had significantly higher slow vital capacity (SVC)/FVC (%), higher EV/FVC (%), shorter ET, shorter ETe, and longer ETp, when compared with those with obstructed. In the obstructed group, ET (r = 0.201, P = 0.016) and ETe (r = 0.496, P < 0.001) positively correlated with FVC, and ETp (r = -0.224, P = 0.007) negatively correlated with FVC. In the restricted group, FVC positively correlated with ETe (r = 0.350, P = 0.004) but not ET and ETp. FVC z-score significantly correlated with total IgE (n = 51, r = -0.349, P = 0.012) and with FEF25-75% z-score (n = 66, r = 0.531, P < 0.001) in the restricted group. The further logistic regression revealed that the risk of restricted increased by 1.12 (95% CI, 1.04-1.22, P = 0.005) with every 1% increase in %ΔFVC. In subjects with restricted and bronchodilation tests, %ΔFVC was significantly associated with FeNO (n = 29, r = 0.386, P = 0.039), FEF25-75% z-score (n = 29, r = -0.472, P = 0.010), and SVC/FVC (%) (n = 19, r = 0.477, P = 0.039) but not with EV/FVC (%), ET, ETe, or ETp (P > 0.05). Conclusion: These findings suggested that "poor FVC effort" does not account for the FVC reduction in asthmatic children. Short ET and high SVC/FVC (%) are characteristics of reduced FVC.

Dataset Information

Edaravone efficacy in amyotrophic lateral sclerosis with reduced forced vital capacity: Post-hoc analysis of Study 19 (MCI186-19) [clinical trial NCT01492686].

Background

Objective

Methods

Results

Conclusion

Publications

Edaravone efficacy in amyotrophic lateral sclerosis with reduced forced vital capacity: Post-hoc analysis of Study 19 (MCI186-19) [clinical trial NCT01492686].

Similar Datasets

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