Early enthusiasm that the MS drug dimethyl fumerate (DMF) might also slow disease progression in amyotrophic lateral sclerosis (ALS) has been curbed as findings from an Australian study showed that people taking the drug had no significant difference in outcomes at three years compared to placebo.
Approved as a first-line treatment for relapsing MS, the medication is thought to lower inflammation and oxidative stress, boosting regulatory T cell levels and suppressing pro-inflammatory T cells. The pathway is also an important pathogenic mechanism in ALS.
Researchers from multiple neurology centres around Australia and led by Professor Steve Vucic, Director of the Brain and Nerve Research Centre at Concord Hospital, investigated the safety and efficacy of the disease modifying treatment in 107 patients with ALS.
Writing in the Annals of Clinical and Translational Neurology, the group said that while the drug was well tolerated among the 72 patients randomised to take it there was no significant change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score compared to the 35 participants in the placebo group over the 36-month follow up period.
But, while there were no significant differences in other secondary outcome measures either including SI, MRC scores, respiratory function, and quality of life scores, Professor Vucic and colleagues said dimethyl fumarate ‘exerted a significant effect’ on the neurophysiological index score – a robust biomarker of disease progression in ALS.
The rate of NI decline was reduced in the dimethyl fumarate group, with the ΔLSM 0.84 (0.51 to 2.22, p = 0.22). Although this difference was not significant, Professor Vucic said the finding suggests preservation of lower motor neuron function. But he added that this would need verification in a larger trial.
“It should be stressed that the present trial did not prespecify power calculations according to changes in NI. Future phase 2 trials could pre-specify NI as an outcome biomarker to determine efficiency of compound at an early stage of their development.”
Overall, dimethyl fumarate did not demonstrate any beneficial effect on survival compared with placebo (p = 0.09; hazard ratio >99), with the majority of participants in the dimethyl fumarate group (93.8%) and all in the placebo group being censored.