November 14, 2019 | News | Living with MS

What is “progression”?

Part 1

When talking about multiple sclerosis, doctors often mention “progression” – a confusing term that refers to different things and whose meaning has changed in recent years.

“Disease progression” implies that an underlying disease process is getting worse. It’s a term used in other areas of medicine such as oncology, where a person with progression knows that their cancer is getting worse. Since no one truly understands how the disease process begins and evolves in MS, “disease progression” is really an appraisal of a person’s level of physical disability. The “progression” is an accumulation of impairments over time rather than an indication that the MS disease process itself is getting worse. It’s akin to aging – a person may become increasingly disabled as they get older, but they wouldn’t be said to be “progressing”.

The term “disability progression” appears more straight-forward. It is more or less synonymous with “disease progression” but without making a claim about the disease process. It means that disability is slowly getting worse, either in the severity of an impairment or in the number of impairments. But even that concept has changed over the past few years into two related but distinct ideas.

A doctor evaluates a person’s level of function during the neurological exam and uses tools, such as the EDSS (for Expanded Disability Status Scale), to assign a disability score (from 0 to 10 in the case of the EDSS). A person’s level of disability can worsen during a relapse (the score increases usually by at least 1 point) then gradually improve over the next few weeks or months.

An oft-cited study reported that about 1 in 4 people will have residual disability two months after a relapse (Lublin and colleagues. Neurology 2003;1:1528-1532). This meant that their EDSS score increased and did not subsequently go down. However, this didn’t take into account that some relapses may take longer to heal. So the idea of “sustained progression” emerged – if an initial worsening EDSS score hadn’t improved in three months’ time, it was called “3-month confirmed disability progression” (CDP). This measure was first used in a Copaxone trial in 1995 and is still commonly used today, even though it’s known to overestimate true “progression”. Clinical trials are now using 6-month CDP as a more rigorous benchmark, although this can also be misleading. For example, a Harvard study found that 30% of people had sustained progression at 6 months, but over a longer observation period, the number who actually sustained their progression dropped to 13% (Healy and colleagues. Mult Scler Int 2013;2013:189624).

A better term for these short-term changes in function is “short-term disability worsening”, which reflects the fluctuating nature of relapsing-remitting MS. A person may be worse off, but that doesn’t necessarily mean their MS has “progressed” in the sense of more irreversible tissue damage in the brain. This is shown by the fact that people with no disability early in the disease process are more likely to show disability worsening (according to the measures used) than older people with greater levels of disability, although it is the older person who is more “progressed”. What is more important is that the older person with disability in this scenario is less likely to improve. So all “worsening” shouldn’t be considered the same in terms of its impact on a person’s life.

Short-term disability worsening is only half of the MS story. While some tissue damage appears to be attributable to inflammatory flare-ups (relapses and MRI lesions), much of it is due to a somewhat different neurodegenerative process. This distinction between inflammation and neurodegeneration is reflected in a new term – PIRA (for progression independent of relapse activity), first coined last year. We’ll look at what PIRA means to progression in part 2 of this article.

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