In short
Progressive relapsing multiple sclerosis is one of the rarest forms of MS, affecting only about 5 percent of people diagnosed with this condition. Understanding treatment options—both established and experimental—can help patients and families navigate this challenging journey with greater confidence and hope.
Key points
- Progressive relapsing MS is the rarest form of multiple sclerosis, affecting only about 5 percent of people with MS and characterized by both steady progression and occasional relapses.
- Corticosteroids like methylprednisolone remain the primary treatment for acute relapses and should be administered promptly to minimize permanent nerve damage.
- Not all symptom worsening indicates a true relapse—pseudoexacerbations caused by heat, infection, or stress can mimic relapses but improve when the trigger is removed.
- Disease-modifying therapy with medications like mitoxantrone can help slow disease progression but is reserved for specific situations due to potential serious side effects.
- Researchers are actively testing promising new therapies including monoclonal antibodies, neuroprotective agents, and remyelinating treatments in clinical trials worldwide.
- The progressive worsening in PRMS is caused by actual nerve damage while relapses are due to inflammation, requiring treatment strategies that address both mechanisms.
- Regular monitoring through clinical exams and MRI scans helps doctors assess treatment effectiveness and make necessary adjustments to the care plan.
- Treatment decisions must be personalized based on disease stage, symptom severity, relapse frequency, and individual patient response to different therapies.
Standard Treatment Approaches
The foundation of treating progressive relapsing multiple sclerosis involves managing both the progressive aspects of the disease and the acute relapse episodes. When a relapse occurs—defined as new symptoms or worsening of existing symptoms that last at least 24 to 48 hours—prompt treatment is essential to minimize permanent damage and accumulation of disability over time.
Corticosteroids are the primary medication used to treat acute relapses. These powerful anti-inflammatory drugs work by reducing inflammation (swelling and immune system activity) in the central nervous system (the brain, spinal cord, and optic nerves). The most commonly prescribed corticosteroid is methylprednisolone, often given under the brand name Solu-Medrol. Another option is dexamethasone, marketed as Decadron. These medications are typically administered through intravenous infusion (delivered directly into the bloodstream through a vein) over a period of three to five days.
In some cases, patients may receive high-dose oral corticosteroids instead of IV treatment, which can be more convenient and equally effective for moderate to severe relapses. After the high-dose treatment period, doctors may prescribe oral prednisone in gradually decreasing doses over one to two weeks. This tapering helps ease the patient off the medication and reduces the risk of side effects from suddenly stopping steroid treatment. The infusions can take place in a hospital, an infusion center, or sometimes even at home with proper support.
While corticosteroids usually lessen the severity and duration of a relapse, they do not appear to affect the long-term progression of the disease itself. Their main benefit is helping patients recover more quickly from acute attacks. Less severe relapses may not require steroid treatment at all, allowing medical teams to reserve these powerful medications for more serious episodes.
For patients who cannot tolerate corticosteroids due to side effects, or for those who haven't responded well to previous steroid treatments, an alternative exists. Adrenocorticotropin hormone (ACTH) preparations, available as Acthar Gel or Purified Cortrophin Gel, act similarly to corticosteroids. These highly purified forms of ACTH in gelatin are approved specifically for treating MS relapses and are given once daily, though research suggests they have similar effectiveness to traditional corticosteroids.
Common side effects of corticosteroid treatment can include increased appetite, weight gain, mood changes, difficulty sleeping, elevated blood sugar levels, and increased blood pressure. Some patients experience stomach upset or fluid retention. Most side effects are temporary and resolve after treatment ends. Long-term or repeated use of corticosteroids carries additional risks, which is why they are reserved for treating acute relapses rather than used continuously.
Disease-modifying therapy is another crucial component of standard treatment. One medication, mitoxantrone, has received approval for treating progressive relapsing MS, along with secondary progressive MS. This drug works by suppressing the immune system, but its use is limited due to potential serious side effects, including heart damage and increased risk of certain blood cancers. Because of these risks, mitoxantrone is typically reserved for patients with aggressive disease who haven't responded to other treatments.
The duration of disease-modifying therapy varies greatly among patients. Some people may remain on the same medication for years if it continues to be effective and well-tolerated. Others may need to switch treatments due to side effects, lack of effectiveness, or changes in their disease course. Regular monitoring through clinical examinations and MRI scans (magnetic resonance imaging, which creates detailed pictures of the brain and spinal cord) helps doctors assess whether treatment is working and when adjustments might be needed.
Treatment in Clinical Trials
Research into new treatments for progressive forms of multiple sclerosis represents one of the most active areas of MS research today. Scientists recognize that progressive MS, including the progressive relapsing subtype, has distinct characteristics that require different therapeutic approaches compared to relapsing-remitting MS. While inflammation plays a major role in relapses, progressive worsening is caused more by nerve damage and loss, a process called neurodegeneration (progressive death and dysfunction of nerve cells).
Several promising therapies are currently being tested in clinical trials. These trials typically progress through three phases. Phase I trials focus primarily on safety, determining whether a new treatment is safe enough to give to humans and what dose might be appropriate. Phase II trials test whether the treatment shows signs of effectiveness against the disease and continue to monitor safety in a larger group of patients. Phase III trials compare the new treatment against standard treatments or placebo in large groups of patients to definitively determine whether it works and is safe enough for widespread use.
One class of medications being studied includes monoclonal antibodies, which are laboratory-made proteins that can target specific parts of the immune system. Some of these target immune cells called B-cells, which play a role in MS disease activity. These medications work by reducing the number or activity of these cells, potentially decreasing both inflammation and disease progression. Several monoclonal antibodies have already been approved for relapsing forms of MS and are being studied to see if they benefit patients with progressive disease.
Another promising area involves medications that may protect nerve cells from damage or help repair the myelin coating around nerves. These neuroprotective and remyelinating therapies represent a fundamentally different approach compared to traditional immune-suppressing medications. Instead of just dampening the immune system, these treatments aim to help the nervous system resist damage or even repair itself. Several compounds with potential neuroprotective effects have shown promise in early studies.
Researchers are also investigating whether certain medications already approved for other conditions might help in progressive MS. This approach, called drug repurposing, can potentially bring treatments to patients faster since safety information already exists for these medications. Examples include drugs originally developed for cancer, heart disease, or other neurological conditions that might also have neuroprotective or anti-inflammatory effects relevant to MS.
Clinical trials for progressive MS face unique challenges compared to trials for relapsing-remitting disease. The slow, gradual worsening that characterizes progressive MS means trials often need to run for longer periods to detect meaningful differences between treatments. Researchers have developed new ways to measure disease progression more sensitively, including measuring brain volume loss (atrophy), testing walking speed and hand function, and measuring levels of proteins in blood that indicate nerve damage.
Many trials are being conducted at medical centers around the world, including locations in the United States, Europe, and other regions. Eligibility for these trials depends on specific criteria, which typically include the type of MS, degree of disability, age range, and other health factors. Patients with progressive relapsing MS might qualify for trials specifically targeting progressive disease or trials focused on managing relapses.
Preliminary results from some trials have been encouraging, showing improvements in measures of disease progression, reduction in relapse frequency, and acceptable safety profiles. However, it's important to understand that experimental treatments remain unproven until trials are complete and results are carefully analyzed. Participation in clinical trials is a personal decision that should be made in consultation with healthcare providers, weighing potential benefits against risks and the time commitment involved.
Most Common Treatment Methods
- Corticosteroid therapy for relapses
- High-dose methylprednisolone (Solu-Medrol) given intravenously over three to five days to reduce inflammation during acute relapses
- Dexamethasone (Decadron) as an alternative corticosteroid option, also given intravenously
- High-dose oral corticosteroids as an alternative to IV treatment for moderate to severe relapses
- Oral prednisone in tapering doses following high-dose treatment to ease patients off steroids
- Treatment typically administered in hospitals, infusion centers, or at home with proper support
- Alternative treatments for relapses
- Adrenocorticotropin hormone (ACTH) preparations including Acthar Gel and Purified Cortrophin Gel
- Used for patients who cannot tolerate corticosteroids or who haven't responded to previous steroid treatments
- Given once daily and specifically approved for treating MS relapses
- Disease-modifying immunosuppressive therapy
- Mitoxantrone approved for treating progressive relapsing MS and secondary progressive MS
- Works by suppressing the immune system to reduce disease activity
- Reserved for patients with aggressive disease due to potential serious side effects including heart damage and increased cancer risk
- Experimental therapies in clinical trials
- Monoclonal antibodies targeting B-cells and other immune system components
- Neuroprotective agents aimed at protecting nerve cells from damage
- Remyelinating therapies designed to help repair the protective myelin coating around nerves
- Repurposed drugs originally developed for other conditions that may have neuroprotective or anti-inflammatory effects
