Progressive multiple sclerosis (MS) refers to forms of MS where disability gradually worsens over time, either from the start (primary progressive MS, PPMS) or following an initial relapsing-remitting phase (secondary progressive MS, SPMS). Treating progressive MS is challenging because many therapies effective in relapsing forms do not significantly halt progression in these types. However, several disease-modifying therapies (DMTs) and other treatments are currently used or under investigation to manage progressive MS and slow disability.
One of the most notable drugs approved specifically for progressive MS is **ocrelizumab** (Ocrevus). It is a monoclonal antibody that targets CD20-positive B cells, a type of immune cell involved in MS inflammation. Ocrelizumab is approved for both PPMS and active SPMS. Clinical evidence shows it can reduce relapse rates in active SPMS and slow disability progression in PPMS. Even in inactive SPMS, some doctors may prescribe it off-label because it appears to slow disability accumulation over time, despite fewer relapses. Other monoclonal antibodies like **natalizumab** (Tysabri) and **ofatumumab** (Kesimpta) are also used mainly for relapsing forms but may be considered in some progressive cases depending on disease activity[1][3][6].
Another oral medication used in active SPMS is **cladribine** (Mavenclad). Originally developed as a chemotherapy agent, cladribine selectively targets lymphocytes, reducing immune attacks on the nervous system. It is typically reserved for patients who have not responded well to at least two other MS drugs. Cladribine is administered in short courses over two years and has shown effectiveness in relapsing MS forms, including active SPMS[1].
Other oral DMTs approved for relapsing MS, such as **teriflunomide** and **fingolimod**, are being studied for their potential in progressive MS. Teriflunomide works by blocking rapid white blood cell growth, a key part of the autoimmune process. Fingolimod traps immune cells in lymph nodes, preventing them from reaching the central nervous system. Fingolimod is particularly interesting because it crosses the blood-brain barrier and may have neuroprotective effects inside the brain and spinal cord. Clinical trials are ongoing to determine if fingolimod can slow progression in PPMS[2].
Beyond these, there are many other DMTs approved for relapsing MS, such as interferons, glatiramer acetate, dimethyl fumarate, and siponimod. Siponimod, in particular, is approved for active SPMS and works similarly to fingolimod by modulating immune cell movement. Choosing the right therapy depends on multiple factors including disease activity, side effects, patient preference (oral vs. injection), and prior treatment response. Sometimes trial and error is necessary to find the best fit[1][3].
For progressive MS, the focus is not only on slowing immune attacks but also on managing symptoms and maintaining function. Corticosteroids may be used to reduce inflammation during relapses, though relapses are less common in progressive forms. Rehabilitation therapies—physical, occupational, speech, and cognitive—play a crucial role in helping people maintain independence and quality of life. Assistive devices like walking aids or wheelchairs may become necessary as disability advances[5][6].
Research is ongoing to develop new treatments targeting the underlying mechanisms of progressive MS. One promising area is **BTK inhibitors**, which modulate immune cell signaling and may reduce both inflammation and neurodegeneration. Clinical trials are underway to evaluate their safety and effectiveness. Other experimental approaches include remyelination therapies, neuroprotective agents, and stem cell treatments, but these are not yet widely available[4][7].
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