Active vs. Non-Active: Categorizing Your SPMS

Once you have transitioned to Secondary Progressive Multiple Sclerosis (SPMS), your medical team will use specific “labels” to describe how your disease is behaving. These labels are not just for your medical records; they are critical tools that help guide which treatments are most likely to work for you ^[1][2].

Doctors evaluate SPMS along two independent dimensions: Activity and Progression. These are not mutually exclusive; you can have one, both, or neither at any given time, and your status can change ^[3][1].

Dimension 1: Activity (Inflammation)

The first dimension tracks whether there is still active, “visible” inflammation occurring in your central nervous system. This is measured by looking at your recent history and your MRI scans over a defined time window—often the last 12 to 24 months, though the exact interval depends on your clinician and specific guidelines ^[4].

• Active SPMS: You are considered “active” if you have had a clinical relapse (an attack) or if your MRI shows new or enlarging T2 lesions or gadolinium-enhancing lesions (spots that light up with contrast dye, indicating a breach in the blood-brain barrier) within that specific window ^[3][2].
• Non-Active SPMS: You are considered “non-active” if you have not had any relapses and your MRI shows no new or enlarging lesions during that same window ^[3]. Note: “Non-active” does not mean all microscopic inflammation has stopped, only that no major new inflammatory events were visible on the scan or in your recent clinical history.

Dimension 2: Progression (Disability Worsening)

The second dimension tracks whether your physical or cognitive disability is increasing over time, regardless of whether you are having relapses or new MRI spots. This is often called Progression Independent of Relapse Activity (PIRA) ^[5][6].

• With Progression: This means your disability is steadily worsening. Your doctor evaluates this by seeing a sustained increase in your EDSS score (usually by 0.5 to 1.0 point) or a 20% decline in tests like the Timed 25-Foot Walk that lasts for at least 3 to 6 months ^[7][8].
• Without Progression: This means that while you still have MS, your level of disability has remained relatively stable over the observation period ^[3].

The Four “States” of SPMS

By combining these dimensions, your doctor can place your disease into one of four categories. These categories can change over time as the disease evolves ^[1].

Why These Labels Matter for Treatment

The distinction between these categories is a major factor in choosing a Disease-Modifying Therapy (DMT).

For Active SPMS (with or without progression), there is still a clear inflammatory component to the disease. Because of this, certain anti-inflammatory DMTs—such as siponimod—have specific indications for active SPMS in many jurisdictions and have been shown in trials to reduce relapses and slow disability progression ^[2][9]. In the major trial for siponimod, the drug reduced the relative risk of confirmed disability progression for those in the “active” subgroup ^[10][9]. Other therapies like cladribine or ozanimod are approved for relapsing forms of MS, which can include active SPMS depending on local regulations ^[11].

For Non-Active SPMS with Progression, the disease involves overlapping processes like neurodegeneration and inflammation behind a closed blood-brain barrier ^[12]. Currently, anti-inflammatory DMTs have shown limited or inconsistent benefits for stopping progression in this group ^[13][14]. If you fall into this group, never stop your current DMT on your own. The decision to stop, switch, or continue a medication is complex and involves your prior response to the drug, your age, comorbidities, and pregnancy plans ^[15][11]. Knowing your category empowers you to have a more specific conversation with your neurologist. Instead of asking “Is my MS getting worse?”, you can ask, “Am I currently active or non-active?” and “What are our specific goals for my treatment plan?” ^{[1] [3]}.