Secondary progressive MS (SPMS) explained: how it starts, how it is diagnosed, and what can be done today

September 5, 2026

SPMS is not a new disease — it is the phase where damage accumulates even without relapses. Here is how the transition from relapsing-remitting MS actually looks, why the diagnosis is always made in hindsight, what PIRA and "smouldering" MS mean, and which drugs genuinely slow progression.

A man in our group spent two years repeating the same sentence: "No relapses, everything is fine." Then he started using a cane. Not after an attack — his leg was simply a little worse each month than the month before. When he finally asked his neurologist what was going on, the answer floored him: "You have probably been in the secondary progressive phase for a couple of years."

That is the hardest part of the SPMS story. The transition has no date, no test that confirms it and no symptom that announces it. You only see it looking backwards.

What secondary progressive MS is

Secondary progressive multiple sclerosis (SPMS) is the phase that follows relapsing-remitting MS (RRMS). "Secondary" means exactly that — nobody is diagnosed with SPMS from the start; it always follows RRMS. Instead of the attack-and-recovery pattern, disability begins to accumulate slowly and steadily, with or without relapses on top.

The classification used today describes SPMS along two separate axes: whether the disease is active (relapses or new MRI lesions) and whether there is progression (measurable worsening over the past year). That is where "active SPMS" and "non-active SPMS" come from — and those labels decide which drugs are even on the table.

How many people transition, and when

Older studies, from before modern treatment, suggested that roughly half of people with RRMS moved into the secondary progressive phase within about ten years and around 90 percent within twenty-five. The average age at transition was about forty.

Those numbers are still quoted everywhere, and they should be read with a lot of caution. They describe cohorts who had no therapy at all, or interferons at best. Newer cohorts, treated early with effective drugs, show noticeably lower and slower transition rates. I do not trust anyone who claims to know the exact figure today — the honest answer is "fewer people, and later, than twenty years ago".

Why the diagnosis is always late

There is no blood test, MRI finding or scan that says: as of today you have SPMS. The diagnosis is retrospective — your neurologist looks at EDSS scores over time and looks for worsening that lasted at least six to twelve months and did not follow a relapse.

In practice that means the diagnosis is often confirmed about three years after progression actually began. Those three years are not harmless, because treatment decisions during them are made against the wrong picture of the disease.

The practical consequence: your own record is worth more than you think. If once every three months you write down how far you can walk without stopping, how long you can stand in the kitchen, whether you now use a cane in situations where you did not before — you have handed your neurologist data he otherwise does not have. I wrote about the early signs in more detail here: [signs MS may be progressing](/blog/signs-ms-may-be-progressing-worry).

> If you have had no relapses for two years but your walking, balance or thinking is clearly worse than it was — that is a conversation to open yourself, not one to wait for.

PIRA and "smouldering" MS — what changed in our understanding

For years the assumption was that disability in MS came entirely from relapses that did not fully recover. Over the past decade that turned out to be wrong. A large share of worsening happens independently of relapses — the literature calls it PIRA (progression independent of relapse activity), and everyone else calls it smouldering MS.

The mechanism differs from a classic relapse. In a relapse, immune cells break through the blood-brain barrier and create a new, active lesion. In PIRA the inflammation is trapped inside the central nervous system: chronic active lesions that slowly expand at the rim, activated microglia, and B cells collecting in the meninges. On MRI these show up as paramagnetic rim lesions, and people who have more of them progress faster.

This also explains the frustration I hear constantly: "I am on treatment, my MRI is stable, and I keep getting worse." Classic DMTs work brilliantly on the peripheral immune system and on relapses, and poorly on inflammation already sealed behind the barrier. If you want to understand what is actually visible on the scans: [what doctors look for on MRI](/blog/what-doctors-look-mri-scans-multiple-sclerosis-detailed-guide).

What daily life looks like in SPMS

There are fewer relapses, sometimes none for years. But what remains slowly intensifies: walking and balance problems, spasticity and spasms, fatigue that has nothing to do with sleep, bladder and bowel trouble, cognitive slowing, pain and numbness.

If recovery after an attack used to bring you back to ninety percent, now it brings you back to seventy — and stays there. That is the psychologically brutal part, because there is no clear enemy to fight. No attack, no hospital admission, no story to tell. Just quiet sliding.

Which is why in this phase symptom management and rehabilitation stop being an add-on and become the main job: [spasticity](/blog/ms-spasticity-muscle-spasms-complete-guide-causes-medication-exercises), [fatigue](/blog/what-ms-fatigue-feels-like-invisible-exhaustion-healthy-people-not) and [cognitive fog](/blog/cognitive-impairment-ms-ms-fog) all have concrete options worth exhausting.

Drugs: what is approved and what actually works

Siponimod (Mayzent) was the first drug licensed specifically for secondary progressive MS. In the EXPAND trial it cut the risk of confirmed disability progression by about 21 percent versus placebo. The benefit was clearest in people with active SPMS — those still having relapses or new lesions. In fully non-active disease the effect was weaker. Patient experiences are collected here: [siponimod in real life](/blog/siponimod-mayzent-ms-patients-say-their-experience).

Tolebrutinib (Cenrifki) is the biggest change in this field in a decade. On 23 June 2026 the European Commission approved it for SPMS without relapses in the previous two years — precisely the group that until now had no option at all. It is a BTK inhibitor that crosses into the central nervous system and acts on microglia, which is to say on the inflammation behind the barrier described above.

The data come from HERCULES: 1,131 people with non-relapsing SPMS, EDSS between 3.0 and 6.5, no relapses for two years, and documented worsening over the preceding twelve months. Six-month confirmed disability progression was reduced by roughly 31 percent (hazard ratio 0.69), and the share of people whose disability confirmedly improved was about double that on placebo (around 10 versus 5 percent). The price is the liver: significant enzyme elevations occurred in about 4 percent, so regular liver monitoring is mandatory, especially in the first months. In the US the drug is not approved for this indication yet. More on the recent approvals: [the newest MS drugs](/blog/latest-ms-drugs-approved-2025-2026-cenrifki-tolebrutinib-pediatric).

The rest of the list is older and narrower: beta interferons and glatiramer acetate carry an active-SPMS indication and only make sense while relapses continue; cladribine and ozanimod are used in active disease; mitoxantrone has been all but abandoned because of cardiotoxicity and leukaemia risk and survives only for exceptional cases. A full overview with dosing and risks: [all MS DMTs in 2026](/blog/all-ms-dmt-drugs-2026-complete-guide).

One rule is worth carrying into the appointment: everything approved today slows progression. No drug stops it and no drug gives back what is already lost. Expectations set to that hurt less than expectations set to the marketing.

The things that are not drugs, and may matter as much

In the progressive phase, exercise stops being a fitness recommendation and becomes therapy. Resistance training in progressive MS has slowed brain atrophy in controlled trials — the detail is here: [strength training and brain atrophy](/blog/resistance-training-slows-brain-atrophy-ms). Alongside it: continuous physiotherapy rather than occasional cycles, control of blood pressure, cholesterol and blood sugar, quitting smoking (of everything you personally control, smoking accelerates progression the most), and treating depression, which here is closer to the rule than the exception.

What to ask your neurologist

- In your judgement, am I in the secondary progressive phase, and since when? - Is my disease currently active (relapses, new or gadolinium-enhancing lesions)? - Does my current drug still make sense, or should it be switched? - Am I a candidate for siponimod or tolebrutinib, and how would I access it here? - How often will we measure EDSS and walking so we can tell whether anything is working?

An SPMS diagnosis is not a sentence and not a switch that flips one morning. It is a name for something already happening, and the only real difference the name makes is that it changes the treatment plan. It took me a long time to accept that the job is no longer "prevent the next attack" but "protect what I can still do today". It sounds like a smaller ambition. It is not.

This article is educational and does not replace examination and advice from your doctor.