Associations between the ALSFRS-R score and urate levels during 12 months of edaravone treatment for amyotrophic lateral sclerosis: Post hoc analysis of ALSFRS-R scores in clinical studies MCI186-16, MCI186-17, and MCI186-19.

INTRODUCTION/AIMS: In this study we examined the relationship between urate levels at baseline and functional change measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score after edaravone treatment.

METHODS

Data from the edaravone trials MCI186-16, MCI186-17, and MCI186-19 were analyzed, including the following treatment sequence groups: edaravone-edaravone (EE, n = 113); edaravone-placebo (EP, n = 45); and placebo-edaravone (PE, n = 146). Subgroups were defined as low baseline urate (below the median value of 4.8 mg/dL) and high baseline urate (≥4.8 mg/dL). The differences in ALSFRS-R total score change and urate change were evaluated using the mixed model for repeated measurement for overall population, by urate-level subgroup, and by trial.

RESULTS

Compared with the PE group, the EE group showed a slower decline in ALSFRS-R score, regardless of the urate baseline level, and a slower decline in urate level in the higher baseline urate subgroup. Smaller changes in ALSFRS-R score and urate were observed in patients diagnosed with "probable, laboratory-supported ALS." There was a positive correlation between changes from baseline to cycle 12 in urate levels and ALSFRS-R score.

DISCUSSION

Edaravone treatment in ALS patients diagnosed with "definite ALS" or "probable ALS" showed slowing of disease progression, regardless of baseline urate level. In addition, because edaravone treatment was associated with a slower decline in urate level in the higher baseline urate subgroup and urate-level changes were associated with changes in ALSFRS-R score, urate level, and/or change may be one indicator in predicting disease progression after edaravone administration.