Post-hoc analysis of randomised, placebo-controlled, double-blind study (MCI186-19) of edaravone (MCI-186) in amyotrophic lateral sclerosis

Figures & data

Table 1. Prespecified primary analysis and post-hoc sensitivity analyses of change in ALSFRS-R total score and CAFS from baseline to the end of cycle 6 (week 24).

Analysis method	Group	Number of patients analysed	Adjusted meanLS mean ± SE	Between-group differences in the adjusted meanLS mean ± SE (95% CI)
ANOVA with Prespecified LOCF^a (primary analysis)	Edaravone	68	−5.01 ± 0.64	2.49 ± 0.76 (0.99, 3.98)	p = 0.0013
	Placebo	66	−7.50 ± 0.66
ANOVA with ALL LOCF^b (sensitivity analysis)	Edaravone	69	−5.04 ± 0.64	2.37 ± 0.75 (0.89, 3.84)	p = 0.0019
	Placebo	68	−7.41 ± 0.65
MMRM (sensitivity analysis)	Edaravone	69	−4.56 ± 0.55	2.81 ± 0.78 (1.27, 4.35)	p = 0.0004
	Placebo	67^c	−7.37 ± 0.57
CAFS (sensitivity analysis)	Edaravone	69	–	41.64 ± 12.30 (17.31, 65.96)	p = 0.0009
	Placebo	68	–

ALSFRS-R = the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale.

ANOVA = analysis of variance.

CAFS = the Combined Assessment of Function and Survival.

CI = confidence interval.

LOCF = last observation carried forward.

LS Mean = least-squares means.

MMRM = mixed model for repeated measures.

SE = standard error.

^a LOCF was applied to the patients who completed cycle 3 (reached 81 days after treatment initiation).

^b LOCF was applied to all randomised patients.

^c One patient in the placebo group, who lacked ALSFRS-R post baseline data needed for MMRM analysis was excluded.

Figure 1. Distributions of changes in ALSFRS-R total score from baseline to the end of cycle 6 (ALL LOCF).

One dot represents one patient. ALSFRS-R = the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. LOCF = last observation carried forward.

Figure 2. Changes in each item of ALSFRS-R score from baseline to the end of cycle 6 (ALL LOCF).

ALSFRS-R = the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. LOCF = last observation carried forward. LS mean = least squares mean. SE = standard error.

Figure 3. (a) Changes in four domains of the ALSFRS-R score from baseline to the end of cycle 6 (ALL LOCF). (b) Changes in four domains of ALSFRS-R score from baseline to the end of cycle 6 in patients with limb onset (ALL LOCF). (c) Changes in four domains of ALSFRS-R score from baseline to the end of cycle 6 in patients with bulbar onset (ALL LOCF).

ALSFRS-R = the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. LOCF = last observation carried forward. LS mean = least squares mean SE = standard error.