Early disability increases risk for secondary progressive multiple sclerosis

Having disability early on in multiple sclerosis (MS) increases the risk of the condition progressing to secondary progressive MS (SPMS), even without relapses, a new study has found.

Researchers also found that beginning a disease-modifying therapy early may decrease the risk of developing SPMS, particularly if an incomplete recovery from a relapse was the cause of the worsened disability.

SPMS is characterised by a worsening of symptoms over time, unconnected to relapses. If incomplete recovery from relapses causes disability to worsen in a person with MS, this is known as relapse-associated worsening (RAW). If the disability worsens independent of relapses, this is known as progression independent of relapse activity (PIRA).

Researchers reviewed data from 10,692 people with RRMS with a mean age of 32 at disease onset. There were 2,059 episodes which contributed to disability recorded in the five years after MS diagnosis. Of these, 60% (1,232) were PIRA and 40% (827) were RAW.

Of the 18% patients who had one or more early episodes, 1,143 (60%) had only PIRA and 697 (37%) had only RAW events. Fifty-six (3%) had both. Most had only one episode of PIRA (97%) or RAW (91%).

Over a mean follow-up of 9.72 years, 1,056 (10%) patients developed SPMS.

Early RAW or PIRA episodes were associated with a greater risk of SPMS. The risk went up by 50% for each episode of early PIRA and by 153% for each episode of early RAW.

Older age at disease onset and being male also increased the risk of SPMS. Use if a high-efficacy DMT lowered that risk by 5% for every 10% of time using a DMT.

People that had both early RAW and PIRA were 6.28 times more likely to go on to develop SPMS than those without early disability. The risk was 3.06 times higher for people with early RAW.  For PIRA, it was 1.4 times greater. While DMTs reduced the effect of early RAW leading to SPMS, this wasn’t the case in early PIRA.

The researchers concluded that early RAW and PIRA are potential determinants and important risk factors for SPMS, and suggested treating these early episodes might delay or even prevent the progression of MS to a more severe form.