Secondary progressive multiple sclerosis (SPMS) is known to be extremely difficult to treat; there are no effective therapies for halting or reversing disability progression in the late disease phase. In an attempt to address this unmet need, the MS-SMART trial – a multi-arm, double-blind, placebo-controlled phase IIb study – compared the safety and efficacy of three different active agents in patients with SPMS.
The treatments under investigation were amiloride (5 mg twice daily), riluzole (50 mg twice daily), and fluoxetine (20 mg twice daily) – which are all repurposed medicaments selected for the study based on a systematic literature review. A total of 445 patients with SPMS (EDSS score 4.0–6.5) were randomised to receive either one of these treatments or a placebo, and were followed up after 24, 48 and 96 weeks. The primary outcome of the study was a change in the rate of brain atrophy, as measured through MRI scans at baseline, and after 24 and 96 weeks. Secondary outcomes included other MRI parameters, such as new T2 lesions, as well as clinical measures, such as disability progression and cognitive decline.
The results showed no statistically significant differences between any of the treatments and placebo in the rate of brain atrophy, disability progression, or cognitive decline. There was a statistically significant decrease in the number of MRI-detected relapses (T2 lesions) after 96 weeks between patients treated with fluoxetine versus placebo (P=0.012). However, Dr Jeremy Chataway, while presenting the study results, alerted healthcare professionals not to over-interpret the benefits of fluoxetine.
While this study showed no significant therapeutic benefit of amiloride, riluzole or fluoxetine in SPMS, it is the world’s first ‘three in one’ multi-arm trial of neuroprotective agents in MS. As Dr Chataway concluded, “15 years of work were completed in 5 years”, and as such the MS-SMART trial lays a template for future trials.
Additionally, in a heartfelt 3-minute video, Dr. Chataway explains the results to those most interested in the outcome, the 445 MS patients who were enrolled in the trial.
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