Tysabri (natalizumab) is a medication primarily approved and used for treating relapsing forms of multiple sclerosis (MS), such as relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS). Its use in progressive MS, especially the non-active or purely progressive forms, is more complex and less straightforward.
Tysabri works as a monoclonal antibody that targets a molecule called α4-integrin on the surface of immune cells. By blocking this molecule, Tysabri prevents immune cells from crossing the blood-brain barrier and attacking the nervous system, which is a key process in the inflammatory phase of MS. This mechanism makes it highly effective in reducing relapses and new inflammatory lesions seen in relapsing forms of MS.
When it comes to **progressive MS**, the disease course is different from relapsing MS. Progressive MS, particularly the non-active form, is characterized more by gradual neurodegeneration and less by active inflammation. Because Tysabri’s effectiveness depends on blocking immune cell migration and inflammation, its benefit in purely progressive MS without active inflammation is limited. However, in **active secondary progressive MS**, where there is still ongoing inflammation and relapses, Tysabri can be used and has been approved for this indication. This means if a patient with progressive MS still shows signs of inflammatory activity—such as new lesions on MRI or clinical relapses—Tysabri might be a suitable treatment option.
The challenge with progressive MS is that as the disease advances, inflammation tends to decrease and neurodegeneration becomes the dominant process. In these later stages, treatments like Tysabri, which target inflammation, may not be as effective. This is why other therapies, including newer drugs like siponimod (Mayzent) and diroximel fumarate (Vumerity), have been developed and approved specifically for active SPMS, aiming to slow progression by modulating immune activity in different ways.
Safety is also a critical consideration with Tysabri. While it is highly effective, it carries a risk of a serious brain infection called progressive multifocal leukoencephalopathy (PML), especially with long-term use. This risk requires careful patient selection and monitoring, which can influence decisions about using Tysabri in progressive MS patients.
In summary, Tysabri is **not typically used for non-active progressive MS** because its mechanism targets inflammation, which is less prominent in this form. However, it **can be used for active secondary progressive MS** where inflammatory activity persists. The decision to use Tysabri in progressive MS depends on the presence of active disease features, prior treatment history, and weighing the benefits against potential risks. For purely progressive MS without relapses or new lesions, other treatment strategies are generally preferred.
