Dr. Ron’s Research Review – February 12, 2020

©

This week’s research review focuses on ultra-high-dose methylcobalamin for ALS

Ultra-high-dose methylcobalamin may prolong survival and retard symptomatic progression without major side effects if started early. (Kaji et al., 2019)
A study published in the Journal of Neurology, Neurosurgery, and Psychiatry evaluated the efficacy and safety of intramuscular ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis (ALS). The Department of Neurology, Tokushima University Hospital, Tokushima, Japan; Miyagi National Hospital, Sendai, Japan. Tokushukai ALS Care Center, Tokushukai, Japan; and Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan conducted the study.
373 patients with ALS (El Escorial definite or probable; laboratory-supported probable; duration ≤36 months) were randomly assigned to placebo, 25 mg or 50 mg of methylcobalamin groups. Allocated drugs were intramuscularly administered twice per week starting from the end of the observation period (12 weeks) and continued for 182 weeks.
The primary endpoints were the time interval to primary events (death or full ventilation support) and changes in the Revised ALS Functional Rating Scale (ALSFRS-R) score from baseline to week 182. Efficacy was also evaluated using post-hoc analyses in patients diagnosed early (entered ≤12 months after symptom onset).
No significant differences were detected in either primary endpoint (minimal p value=0.087). However, post-hoc analyses of methylcobalamin-treated patients diagnosed and entered early (≤12 months' duration) showed longer time intervals to the primary event (p<0.025) and less decreases in the ALSFRS-R score (p<0.025) than the placebo group. The incidence of treatment-related adverse events was similar and low in all groups.
Although ultra-high-dose methylcobalamin did not show significant efficacy in the whole cohort, this treatment may prolong survival and retard symptomatic progression without major side effects if started early. (Kaji et al., 2019)

 

Dr. Ron

 


Articles

 

Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study.
            (Kaji et al., 2019)  Download
OBJECTIVE:  To evaluate the efficacy and safety of intramuscular ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis (ALS). METHODS:  373 patients with ALS (El Escorial definite or probable; laboratory-supported probable; duration ≤36 months) were randomly assigned to placebo, 25 mg or 50 mg of methylcobalamin groups. The primary endpoints were the time interval to primary events (death or full ventilation support) and changes in the Revised ALS Functional Rating Scale (ALSFRS-R) score from baseline to week 182. Efficacy was also evaluated using post-hoc analyses in patients diagnosed early (entered ≤12 months after symptom onset). RESULTS:  No significant differences were detected in either primary endpoint (minimal p value=0.087). However, post-hoc analyses of methylcobalamin-treated patients diagnosed and entered early (≤12 months' duration) showed longer time intervals to the primary event (p<0.025) and less decreases in the ALSFRS-R score (p<0.025) than the placebo group. The incidence of treatment-related adverse events was similar and low in all groups. CONCLUSION:  Although ultra-high-dose methylcobalamin did not show significant efficacy in the whole cohort, this treatment may prolong survival and retard symptomatic progression without major side effects if started early. TRIAL REGISTRATION NUMBER:  NCT00444613.

 

References

Kaji, R, et al. (2019), ‘Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study.’, J Neurol Neurosurg Psychiatry, 90 (4), 451-57. PubMed: 30636701