Introduction 

Treatment options for MS have evolved significantly over the past 30 years. Prior to 1993, we could only offer corticosteroids and chemotherapy in the hope of influencing the course of the disease. As of 2025, there are 16 different medicines registered in Belgium for the treatment of Relapsing-Remitting Multiple Sclerosis (RRMS). These are available in various forms such as tablets, injections and infusions. Two of them can also be used in progressive forms of MS when there is evidence of inflammatory activity (ocrelizumab in primary progressive MS, siponimod in secondary progressive MS). 

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Viral hypothesis and the emergence of interferon 

Researchers have for several decades suspected that viruses play a role in the development of MS. The antiviral effects of the human protein interferon formed the basis for research in the 1970s and 1980s. Encouraging results from a large-scale, randomised, double-blind, placebo-controlled trial of interferon beta-1b in RRMS in 1993 marked a milestone in MS treatment. In July 1993, interferon beta-1b was approved by the FDA as the first medicine for RRMS. 

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Animal model for MS 

Experiments on laboratory animals, primarily mice, have contributed to a better understanding of disease mechanisms and the testing of new MS treatments. Induced inflammation of the central nervous system, known as autoimmune encephalomyelitis, serves as a model for MS. Glatiramer acetate, a mixture of synthetic proteins resembling myelin, has been shown to mislead the immune system in animal studies. Based on promising results in people with RRMS, this treatment was approved by the FDA in October 1995. Approval in Europe followed a few years later.   

Medicines for immune-mediated diseases 

Encouraging results in Crohn’s disease, an inflammatory bowel condition, led to large-scale studies conducted on RRMS with natalizumab. The hypothesis that monoclonal antibodies targeting proteins on the surface of inflammatory cells could inhibit their passage through the blood–brain barrier was confirmed. This highly effective (second-line) infusion treatment has been available in Belgium for RRMS since December 2007. Fingolimod, the first oral treatment for RRMS, followed in February 2012 as a second-line option, as it reduced inflammation significantly by retaining lymphocytes in the lymphoid organs. Earlier research with this substance had focused on preventing rejection after kidney transplantation. This class of drugs has since been expanded to include ozanimod and ponesimod (first-line treatments for RRMS) and siponimod (for secondary progressive MS). 

Expansion of treatment options in RRMS

First-line treatments were expanded to include teriflunomide (2013) and dimethyl fumarate (2014), which were derived from medicines for psoriasis and rheumatism, respectively, with various immunomodulatory effects.  

Three different monoclonal antibodies targeting a surface protein (CD20) on B lymphocytes were added in second line therapy: ocrelizumab, ofatumumab and ublituximab. Their intravenous or subcutaneous administration leads to a marked suppression of inflammatory processes in RRMS. A measurable effect on progression was also demonstrated with ocrelizumab in primary progressive MS with inflammatory activity. Cladribine, an oral induction therapy administered in two yearly doses (half the dose in year 1, and the other half in year 2), primarily targets rapidly dividing immune cells in RRMS. Alemtuzumab is an intravenous third-line induction therapy with monoclonal antibodies against CD52+ immune cells. These medicines were originally investigated for MS because of their efficacy in haematological cancers. 

What these medicines do and do not do 

Current MS medicines successfully suppress the overactive immune response. There are however drawbacks and risks associated with immunosuppression. Choosing the most suitable treatment for an individual is not straightforward due to the diverse mechanisms of action and the unpredictable course of the disease. Treatment response cannot be reliably predicted either at present. Unfortunately, no medication has yet proven significantly effective in slowing the gradual progressive course, independent of inflammation. A new class of drugs, the BTK inhibitors, may offer hope on this front. To be continued! 

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Marie B D’hooghe

National MS Centre, Melsbroek 

Faculty of Medicine and Pharmacy, VU Brussel