In short
Secondary progressive multiple sclerosis represents a challenging stage in the journey of living with MS, where symptoms gradually worsen over time and the goal of treatment shifts toward slowing disease progression, managing symptoms, and maintaining quality of life for as long as possible.
Key points
- Secondary progressive MS develops in many people who initially had relapsing-remitting MS, typically 10 to 25 years after first diagnosis, marking a shift from episodic flares to gradual worsening of symptoms
- Treatment focuses on slowing progression, managing symptoms, and maintaining independence rather than preventing relapses as in earlier disease stages
- Several disease-modifying drugs including siponimod, cladribine, and ublituximab-xiiy are specifically approved for treating secondary progressive MS
- Modern treatments have significantly delayed the transition from relapsing-remitting to secondary progressive MS compared to before the 1990s when no disease-modifying drugs existed
- SPMS can follow four different courses: active with progression, nonactive with progression, active without progression, and nonactive without progression, and people may shift between these patterns
- Rehabilitation including physical therapy, occupational therapy, and cognitive support plays an essential role in maintaining function and quality of life
- Clinical trials are actively testing new therapies that aim to protect nerve cells and promote myelin repair, offering hope for future treatment options
- Mobility aids like braces, canes, walkers, or scooters can help maintain independence, and about two-thirds of people with SPMS maintain walking ability
How Treatment Helps Manage Secondary Progressive Multiple Sclerosis
When someone with multiple sclerosis transitions from relapsing-remitting disease to secondary progressive MS, their treatment needs change significantly. The main focus of treating secondary progressive multiple sclerosis is to slow down the worsening of symptoms, help maintain independence, and improve overall quality of life. Unlike the earlier stage of MS where treatments target sudden flare-ups, care for SPMS addresses the gradual accumulation of disability that occurs even without clear relapses.
Treatment plans for secondary progressive MS depend heavily on the individual characteristics of each patient. Doctors consider whether the person still experiences occasional relapses, how quickly their disability is progressing, and which symptoms are most troublesome in daily life. Some people with SPMS continue to have periodic flare-ups alongside gradual worsening, a pattern called active SPMS. Others experience steady progression without any relapses, known as nonactive SPMS.
The transition from relapsing-remitting MS to secondary progressive typically happens between 10 and 25 years after the initial diagnosis, often when people are in their 40s or 50s. This progression reflects ongoing nerve damage in the brain and spinal cord that continues even when the intense inflammatory attacks of earlier disease have decreased. While there is currently no cure for secondary progressive MS, medical societies recommend a combination of approved medications, symptom management strategies, and rehabilitation therapies to help patients maintain their abilities and independence.
Standard Treatment Approaches for Secondary Progressive Multiple Sclerosis
The foundation of treating secondary progressive MS involves medications called disease-modifying drugs, or DMDs. These medicines work by affecting the immune system to slow down the progression of disability. The specific drug chosen depends on whether a person still experiences relapses and how active their disease appears on brain scans.
For patients who continue to have occasional relapses alongside progression, doctors often continue or adjust the disease-modifying therapies that were used during the relapsing-remitting phase. These include medications such as alemtuzumab, cladribine, fingolimod, glatiramer acetate, natalizumab, ocrelizumab, ofatumumab, and various forms of interferon beta. Each of these substances works through different mechanisms to reduce immune system attacks on the protective myelin coating around nerve fibers.
Among the medications specifically approved for secondary progressive MS, siponimod (marketed as Mayzent) stands out as an important option. This drug affects certain immune cells called lymphocytes, preventing them from moving into the brain and spinal cord where they can cause damage. Clinical trials have shown that siponimod can slow disability progression in people with active secondary progressive MS.
Another medication approved specifically for SPMS is cladribine (Leustatin, Mavenclad). This drug works by selectively reducing certain types of white blood cells that contribute to the disease process. It is given as a short course of treatment over two years. The medication ublituximab-xiiy (Briumvi) has also received approval for treating SPMS and works by targeting specific immune cells.
For people experiencing active relapses during the progressive phase, short-term treatment with corticosteroids can help reduce inflammation and shorten the duration of flare-ups. These powerful anti-inflammatory medications are typically given for brief periods because longer use can lead to side effects such as upset stomach, rapid heartbeat, facial flushing, mood changes, and weakening of bones over time.
Beyond disease-modifying drugs, treatment for secondary progressive MS includes comprehensive symptom management. Physical therapy plays a crucial role in maintaining strength, balance, and mobility. Physical therapists design exercise programs tailored to each person's abilities and limitations, helping them stay as active and independent as possible. Rehabilitation may also include occupational therapy to help with daily activities, speech therapy for communication difficulties, and cognitive therapy for thinking and memory problems.
The duration of treatment varies greatly among individuals. Many people with SPMS continue taking disease-modifying medications for years as long as the drugs remain effective and tolerable. Regular monitoring through neurological examinations and brain scans helps doctors assess whether treatments are working and adjust the plan as needed.
Promising Treatments Being Tested in Clinical Trials
Research into new therapies for secondary progressive multiple sclerosis has intensified in recent years because treatment options remain limited compared to relapsing-remitting MS. Clinical trials are exploring innovative approaches that target different aspects of the disease process beyond just controlling inflammation.
Many experimental treatments focus on protecting nerve cells from further damage, a strategy called neuroprotection. Scientists have learned that in secondary progressive MS, ongoing nerve fiber damage happens even when inflammation decreases. This understanding has led researchers to test therapies that might shield nerve cells or help repair damaged myelin, rather than only suppressing the immune system.
Clinical trials for SPMS typically progress through several phases. Phase I trials test whether a new drug is safe and determine appropriate doses in small groups of people. Phase II trials expand testing to larger groups to evaluate effectiveness and continue monitoring safety. Phase III trials compare the new treatment against standard care or placebo in hundreds or thousands of participants to confirm effectiveness and collect comprehensive safety information before seeking approval from regulatory authorities.
Some promising molecules being investigated include agents that work through different mechanisms than current approved drugs. Researchers are testing substances that might reduce certain types of immune cells more selectively, potentially offering benefits with fewer side effects. Other experimental approaches aim to enhance the body's natural ability to repair myelin damage or protect nerve fibers from degeneration.
Clinical trials for secondary progressive MS are conducted at medical centers across the United States, Europe, and other regions worldwide. Eligibility for participation typically depends on factors such as confirmed diagnosis of SPMS, degree of disability measured on standardized scales, and whether the disease shows evidence of active progression. Some trials specifically enroll people with active disease (those who still have occasional relapses or new lesions on brain scans), while others focus on nonactive progressive forms.
One challenge in conducting trials for SPMS is that disease progression happens slowly over months and years, making it difficult to measure whether experimental treatments are working. Researchers have worked to develop better definitions of progression and more sensitive ways to detect changes in disability. This includes tracking walking ability, upper limb function, cognitive performance, and brain volume changes on MRI scans over time.
The results from some recent clinical trials have shown modest but meaningful benefits. Certain experimental therapies have demonstrated ability to slow the rate at which people lose walking speed or accumulate additional disability points on standard measurement scales. Even small delays in progression can significantly impact quality of life and independence for people living with SPMS.
Most common treatment methods
- Disease-Modifying Drugs
- Siponimod (Mayzent) - affects lymphocytes to prevent them from entering the central nervous system, approved specifically for active secondary progressive MS
- Cladribine (Leustatin, Mavenclad) - selectively reduces certain white blood cells involved in the disease process, given as short course over two years
- Ocrelizumab (Ocrevus) - targets specific immune cells called B cells
- Ofatumumab (Kesimpta) - another B cell targeting therapy
- Ublituximab-xiiy (Briumvi) - approved for treating SPMS by targeting specific immune cells
- Interferon beta preparations - reduce immune system attacks on myelin
- Natalizumab (Tysabri) - prevents immune cells from crossing into the brain and spinal cord
- Fingolimod (Gilenya) - keeps certain immune cells trapped in lymph nodes
- Anti-Inflammatory Therapy for Relapses
- Corticosteroids (such as methylprednisolone) - reduce inflammation during acute flare-ups
- Given for short periods to minimize side effects including stomach upset, rapid heartbeat, mood changes, and bone weakening
- Rehabilitation Therapies
- Physical therapy - maintains strength, balance, and walking ability through customized exercise programs
- Occupational therapy - helps adapt daily activities and home environment
- Speech therapy - addresses communication and swallowing difficulties
- Cognitive rehabilitation - supports thinking, memory, and information processing
- Symptom Management
- Medications for muscle stiffness and spasms
- Treatments for bladder and bowel control issues
- Therapies for fatigue management
- Vision problem treatments
- Pain management strategies
- Mobility Support
- Ankle-foot orthosis (AFO) braces to support walking
- Functional electrical stimulation devices to activate leg muscles
- Canes and walkers for stability
- Scooters or wheelchairs for longer distances or fatigue management
