Secondary progressive multiple sclerosis (SPMS)

Last updated Aug. 30, 2022, by Marisa Wexler, MS
Fact-checked by Ines Martins, PhD

Multiple sclerosis (MS) is an inflammatory disorder in which the immune system attacks parts of the central nervous system, interfering with normal neuronal signaling. The disease is divided into several types based on how its symptoms manifest and progress over time.

Secondary progressive multiple sclerosis (SPMS) is a form of MS that develops after the initial relapsing-remitting type in most patients.

What is secondary progressive MS?

The majority of MS patients are initially diagnosed with relapsing-remitting MS (RRMS), a form of the neurological disease that’s characterized by relapses, in which symptoms suddenly worsen, interspersed with periods of remission, where symptoms ease and remain stable.

Many people with RRMS eventually develop SPMS, which is defined by symptoms gradually worsening over time, even in the absence of relapse activity. Some people with SPMS still experience relapses, but symptoms do not go away entirely and will continue to grow more severe over time, even in periods of relative remission.

SPMS can be classified as active or nonactive, based on whether or not the individual experiences disease relapses or has evidence of new brain lesions. It also can be classified as with or without progression, based on patterns of disability accumulation over time.

Symptoms of SPMS

As in other MS types, the specific symptoms of secondary progressive MS can vary markedly between patients, depending on which parts of the brain and spinal cord are most affected.

People with SPMS are generally more likely than those with RRMS to experience difficulty walking and coordination. Other common symptoms in SPMS include:

• fatigue
• unusual sensations like numbness or tingling, referred to as dysesthesias
• vision problems
• spasticity or muscle stiffness
• trouble regulating the bladder and bowel
• cognitive challenges and emotional difficulties

Onset: Transitioning from RRMS to SPMS

Historically, almost all people with RRMS have developed SPMS. Exactly what causes the progression to SPMS is not completely understood, but the mechanisms of disease progression seem to differ between the two subtypes.

Whereas RRMS symptoms are thought to be driven by active inflammation that causes damage to nerve cells in the brain, SPMS is mainly driven by the progressive loss of the damaged nerve cells, mostly without active inflammation.

Consistently, RRMS patients generally exhibit more new lesions or lesions with active inflammation, while those living with SPMS tend to present more inactive or chronic active lesions.

The timing for SPMS transition is different from person to person, but modern disease-modifying treatments (DMTs) can markedly reduce the number of patients who go on to develop SPMS — while also extending the time for that transition to occur.

Without MS treatment, approximately half of RRMS patients are estimated to progress to SPMS within a decade of disease onset. About 90% will develop MS of this type within 25 years of an RRMS diagnosis. Current estimates suggest, however, that fewer than 10% of patients who receive treatment convert to SPMS over a median of three decades.

On the other hand, factors that have been linked with a faster onset of SPMS include:

• older age at MS onset
• male sex
• experiencing many relapses or rapidly worsening disability early on in the disease
• longer disease duration
• greater numbers of lesions
• spinal cord involvement
• smaller brain volume

Diagnosis of SPMS

There are no formal diagnostic criteria that define when RRMS transitions into SPMS. Instead, the diagnosis of secondary progressive disease is made after carefully reviewing the progression of the disorder in the preceding months and years.

Because RRMS and SPMS form a continuum of the disease without a clear-cut boundary, it is common for people to experience a period of diagnostic uncertainty during the transition to SPMS. For most patients, it can take a few years before the diagnosis of SPMS is established.

Generally, at least six months of continual disease progression, independent of relapses, must be noted before a person with RRMS is considered to have progressed to SPMS. But there is some variability and disagreement among clinicians as to how to define SPMS — for example, some doctors only will diagnose SPMS if the patient has reached a certain magnitude of disability.

In addition to a review of symptom history, neurological and clinical assessments — such as MRI scans to look for disease lesions, or a lumbar puncture to check for signs of inflammation in the spinal fluid — may be helpful in establishing the diagnosis of SPMS.

Although quite rare, it is possible to be diagnosed with SPMS without ever having been diagnosed with RRMS. In these individuals, clinical evidence indicates that the initial RRMS stage had occurred, but it was not recognized or diagnosed as RRMS, and the patient had already transitioned to SPMS by the time a diagnosis is confirmed.

Treatment of SPMS

The majority of MS disease-modifying therapies approved by the U.S. Food and Drug Administration are indicated for relapsing forms of MS, which include clinically isolated syndrome (CIS), RRMS, and active SPMS.

That means that, for SPMS patients who still experience occasional relapses, a number of DMTs are available in the U.S. These treatments do not cure SPMS, but they have been proven to reduce relapse frequency and delay disability progression in clinical trials. They include:

• Aubagio (teriflunomide)
• Avonex (interferon beta-1a)
• Bafiertam (monomethyl fumarate)
• Betaseron (interferon beta-1b)
• Copaxone (glatiramer acetate injection)
• Extavia (interferon beta-1b)
• Gilenya (fingolimod)
• Kesimpta (ofatumumab)
• Lemtrada (alemtuzumab)
• Mavenclad (cladribine)
• Mayzent (siponimod)
• mitoxantrone
• Ocrevus (ocrelizumab)
• Plegridy (peginterferon beta-1a)
• Ponvory (ponesimod)
• Rebif (interferon beta-1a)
• Tecfidera (dimethyl fumarate)
• Tysabri (natalizumab)
• Vumerity (diroximel fumarate)
• Zeposia (ozanimod)

Note that in Europe and other markets, however, some of these therapies are approved only for RRMS, and not active SPMS or CIS.

As for nonactive SPMS, where patients do not experience any relapse activity, mitoxantrone is the only disease-modifying medication that is approved in the U.S.

Relapses in SPMS tend to be less frequent and cause less drastic changes in symptom severity than in the RRMS stage. But people with SPMS can sometimes experience a severe relapse that causes significant disability or requires hospitalization.

In those cases, treatment with anti-inflammatory medications may be given to help ease symptoms and resolve the exacerbation faster. These treatments include:

• Hormones called glucocorticoids
• Adrenocorticotropic hormone (ACTH)-based therapies
• Plasma exchange, known as plasmapheresis

Finally, people with SPMS and other forms of the disease may benefit from a number of other therapies that help manage specific SPMS symptoms, such as depression, muscle spasms, fatigue, or nerve pain.

Outlook of SPMS

The prognosis of SPMS varies substantially from person to person, depending on factors like whether or not the patient experiences relapses and, if so, how frequently they occur. In general, a faster progression from RRMS to SPMS is associated with a poorer long-term prognosis.

Once patients are confirmed to have progressed to SPMS, it’s recommended they talk to their healthcare providers about whether it makes sense to adjust their care plan to help manage the new disease course. This may include changes in treatment, lifestyle adjustments like quitting smoking and adhering to healthy diets, and physical or occupational therapy to make managing symptoms easier in daily life.

Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.