Multiple sclerosis is an immune-mediated inflammatory disease of the central 
nervous system characterised by demyelination, neuroaxonal loss and a 
heterogeneous clinical course. Multiple sclerosis presents with different 
phenotypes, most commonly a relapsing-remitting course and, less frequently, a 
progressive accumulation of disability from disease onset (primary progressive 
multiple sclerosis). The majority of people with relapsing-remitting multiple 
sclerosis, after a variable time, switch to a stage characterised by gradual 
neurological worsening known as secondary progressive multiple sclerosis. We 
have a limited understanding of the mechanisms underlying multiple sclerosis, 
and it is believed that multiple genetic, environmental and endogenous factors 
are elements driving inflammation and ultimately neurodegeneration. Axonal loss 
and grey matter damage have been regarded as amongst the leading causes of 
irreversible neurological disability in the progressive stages. There are over a 
dozen disease-modifying therapies currently licenced for relapsing-remitting 
multiple sclerosis, but none of these has provided evidence of effectiveness in 
secondary progressive multiple sclerosis. Recently, there has been some early 
modest success with siponimod in secondary progressive multiple sclerosis and 
ocrelizumab in primary progressive multiple sclerosis. Finding treatments to 
delay or prevent the courses of secondary progressive multiple sclerosis is an 
unmet and essential goal of the research in multiple sclerosis. In this review, 
we discuss new findings regarding drugs with immunomodulatory, neuroprotective 
or regenerative properties and possible treatment strategies for secondary 
progressive multiple sclerosis. We examine the field broadly to include trials 
where participants have progressive or relapsing phenotypes. We summarise the 
most relevant results from newer investigations from phase II and III randomised 
controlled trials over the past decade, with particular attention to the last 5 
years.