For many people, multiple sclerosis (MS) starts as relapsing-remitting MS (RRMS). Over time, RRMS may transition into secondary progressive MS (SPMS), a type of MS in which symptoms and disability gradually worsen. That transition can feel frustrating and uncertain, especially if treatments that once worked don’t seem to work as well anymore.

Doctors may recommend disease-modifying therapies (DMTs) for some people with SPMS, especially active SPMS, to help reduce relapses (periods when MS symptoms suddenly get worse or new symptoms appear) and slow disability progression.

Some DMTs are specifically approved for SPMS. Others are approved for relapsing forms of MS — sometimes called active forms of MS — which can include active SPMS in the United States.

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Active SPMS means there are signs of ongoing inflammation, such as relapses or new lesions (areas of damage) seen on MRI scans.

Here’s a closer look at which medications are approved for SPMS, how they’re taken, and why your doctor may recommend one option over another.

When Is SPMS Diagnosed?

Doctors diagnose SPMS when someone who previously had RRMS begins having gradual, steady worsening of symptoms or disability over time, with or without relapses. This change often happens gradually, which can make it hard to pinpoint exactly when RRMS becomes SPMS.

You may also hear these terms:

• Active SPMS — SPMS with signs of ongoing inflammation, such as relapses or new lesions (areas of damage) on MRI scans
• Inactive SPMS — SPMS without new relapses or new MRI activity

That distinction matters because many DMTs work best when inflammation is still active. Some people with SPMS still experience occasional relapses, while others notice a slow worsening of walking, balance, or fatigue over time without obvious flare-ups.

DMTs Approved for Active SPMS

The U.S. Food and Drug Administration (FDA) approves many DMTs for relapsing forms of MS, which include active SPMS. Some are injected under the skin, some are pills, and some are given by intravenous (IV) infusion.

Siponimod

Siponimod (Mayzent) is one of the DMTs with the most directly relevant clinical trial evidence for active SPMS. It was approved by the FDA in 2019 for relapsing forms of MS, including active SPMS.

A major study called EXPAND found siponimod lowered the risk of confirmed disability progression by 21 percent compared with a placebo (an inactive treatment).

However, it’s important to note that not all DMTs approved for active SPMS have been studied in SPMS populations in the same way. This makes it hard for health experts to say whether siponimod is more effective than other approved DMTs for active SPMS.

Siponimod is a once-daily pill. Doctors may recommend it when a person has active SPMS, especially if they have relapses or new lesions on MRI scans.

Highly Effective Biologic Treatments

Highly effective biologic DMTs — treatments made from living cells or proteins — may be recommended when doctors are trying to get better control of relapses and MRI activity in active SPMS.

Highly effective biologic DMTs include:

• Alemtuzumab (Lemtrada) — Usually reserved for people who haven’t responded well to at least two other DMTs because of its serious safety risks and monitoring requirements
• Natalizumab (Tysabri) — Given by IV infusion and may help reduce relapses and new MRI activity
• Ocrelizumab (Ocrevus) — Targets B cells (immune cells involved in MS inflammation) and is given by IV infusion every six months after the first two starting doses
• Ofatumumab (Kesimpta) — Also targets B cells, but is given as a monthly injection at home
• Ubilituximab-xiiy (Briumvi) — Also targets B cells and is given by IV infusion every six months after starting doses

Oral MS Therapies

Several oral medications (drugs taken by mouth) are approved for relapsing forms of MS, including active SPMS:

Cladribine

Cladribine (Mavenclad) is generally considered one of the higher-efficacy oral options. It’s taken in short treatment courses over two years instead of every day long term, though regular blood monitoring is needed.

S1P Receptor Modulators

Sphingosine-1-phosphate (S1P) receptor modulators help keep certain immune cells from reaching the brain and spinal cord. They’re generally considered highly effective oral therapies.

S1P receptor modulators include:

• Fingolimod (Gilenya)
• Ozanimod (Zeposia)
• Ponesimod (Ponvory)

Fumarate Therapies

Fumarates may help reduce relapses and new MRI activity.

This group of drugs includes:

• Dimethyl fumarate (Tecfidera)
• Diroximel fumarate (Vumerity)
• Monomethyl fumarate (Bafiertam)

Diroximel fumarate may cause fewer stomach-related side effects for some people than dimethyl fumarate.

Teriflunomide

Teriflunomide (Aubagio) is a once-daily medication that works by slowing the activity of certain immune cells involved in MS. It’s generally considered a moderate-efficacy option and requires liver monitoring.

Interferons

Interferons are older injectable therapies still used in some people with active SPMS. They may be recommended when disease activity is milder, or when someone has remained stable on interferon treatment for years.

FDA-approved interferon options for relapsing forms of MS, including active SPMS, are:

• Interferon beta-1a (Avonex, Rebif)
• Interferon beta-1b (Betaseron)
• Peginterferon beta-1a (Plegridy)

These medications are given by injection on different schedules, depending on the product.

While these older drugs are generally considered less effective than many newer therapies, some people continue to do well on interferons with stable symptoms and MRI results. They may also be an option for people who are cautious about medication risks or who haven’t tolerated newer treatments well.

Glatiramer Acetate

Glatiramer acetate (Copaxone, Glatopa) may help change how the immune system responds in MS, although its exact mechanism isn’t fully understood. It’s given by injection under the skin.

Glatiramer acetate has a long safety track record and is still used in some people with relapsing forms of MS, which can include active SPMS. It’s generally considered less effective than many newer therapies for preventing relapses and MRI activity.

Glatiramer acetate stands out from the other DMTs, however, because it does not require the same routine lab monitoring as many other MS treatments and has safety data for use during pregnancy and breastfeeding.

Mitoxantrone

Mitoxantrone is an older infusion therapy that’s still FDA-approved for SPMS, progressive-relapsing MS, and worsening relapsing-remitting MS. It’s given through an IV infusion four times a year.

Today, mitoxantrone is used much less often because it can cause serious side effects, including heart damage and certain blood cancers. Because of these risks, doctors usually reserve mitoxantrone for severe cases when other treatment options haven’t worked well enough.

Why Your Doctor Might Recommend One Drug Over Another

SPMS affects each person differently.

Someone whose MRI shows active inflammation may benefit from stronger immune therapy. Another person with inactive SPMS may focus more on symptom management, physical therapy, and quality of life.

Doctors also consider safety, infection risk, pregnancy plans, monitoring needs, and convenience. Someone who dislikes needles may prefer pills, while another person may prefer infusions every few months instead of remembering daily medication.

Insurance coverage, cost, and access can also play a role in treatment decisions.

Choosing a Treatment That Fits Your Life

SPMS treatment has improved significantly in recent years. People with active SPMS now have more options, including newer drugs like siponimod and B-cell therapies.

Still, treatment decisions are individualized. Your doctor may recommend a DMT based on your MRI results, relapse history, overall health, and treatment goals.

Your preferences matter, too. Whether your priority is fewer relapses, staying mobile longer, avoiding frequent clinic visits, or limiting side effects, those conversations can help guide your healthcare in the best direction for you.

Join the Conversation

On MyMSTeam, people share their experiences with secondary progressive MS, get advice, and find support from others who understand.

Have you talked with your neurologist about whether your SPMS is considered active or inactive and how that affects your treatment options? Let others know in the comments below.