OBJECTIVES : While various therapies have been studied in relapsing-remitting multiple sclerosis populations, few therapies have been studied in secondary progressive multiple sclerosis (SPMS). The objective of this review was to assess clinical efficacy, safety and tolerability of pharmacological treatments for patients with SPMS

METHODS : Embase, MEDLINE and the Cochrane Library were searched until 17 October 2018 for comparative trials assessing DMTs in adults with SPMS. Health technology assessment agency websites, key conference proceedings, and grey literature were also screened. Study quality was assessed using National Institute for Health and Care Excellence (NICE) recommended critical appraisal checklists

RESULTS : Out of 3478 citations screened, 23 studies were included; of these, 18 were randomized controlled trials (RCTs), and the remaining were observational. Siponimod was the only intervention to show a significant impact on both 3- and 6-month confirmed disability progression (CDP) compared to placebo. For interferon β-1a, no significant difference was seen in 3- and 6-month CDP, while for interferon β-1b, results were significantly better vs. placebo for CDP-3, while inconsistent results were reported for CDP-6 (1 study reported significant improvement and the other not). One included study for natalizumab vs. placebo did not show statistical significance for CDP-6. In terms of annualized relapse rates (ARR), a significant relapse reduction vs. placebo was seen for interferon (two studies for interferon β-1a, and one for interferon β-1b), natalizumab and siponimod. One study included on adipose-derived mesenchymal stem cells was not powered to demonstrate efficacy differences. Idebenone demonstrated no significant change in disability and neurophysiological parameters. All treatments were generally well tolerated

CONCLUSIONS : Findings from this SLR suggest an improvement in outcomes on treatment with some DMTs compared to placebo. In the absence of active controlled RCTs, indirect comparisons are needed to assess the comparative efficacy of treatments