Assessing disability – the great disconnect
A major focus of MS clinic visits is now the evaluation of what is called ‘progression independent of relapse activity’ (PIRA). This reflects the growing recognition that only a small proportion of a person’s accumulating disability (called progression) is due to relapses – the recurring episodes of feeling worse that have always been the hallmark of multiple sclerosis. These relapses – however miserable they can make a person feel – are not the primary cause of the significant impairments that can occur while living with MS. Instead, there is a more subtle type of inflammation in the brain and spinal cord that damages nerve fibres and causes most of the disability that may develop.
The notion of PIRA dates back to an analysis of Ocrevus studies that showed that about 1 in 5 people developed worsening disability despite taking an MS medication that was potently suppressing relapses and MRI lesions (Kappos and colleagues. JAMA Neurol 2020;77:1132-1140). In 80% of cases when people experienced an episode of worsening disability, it was at a time when they were not having relapses. So disability was reimagined as either being due to relapses (called relapse-associated worsening, or RAW), or not being associated with relapses (or PIRA). This binary view is somewhat arbitrary since it presupposes that PIRA does not occur during relapses. But what the RAW/PIRA distinction did achieve was to unmask the signal of slow neurodegeneration when the static of relapses was filtered out.
PIRA also upended the idea that the accumulating damage caused by relapses is what eventually results in disability. Rather, PIRA can occur at the very beginning of the MS disease process in some people (Lublin and colleagues. Brain 2022;145:3147-3161). This has prompted researchers to investigate how PIRA starts, how it develops and how medications might slow down this process. Many MS medications have little impact on PIRA. However, recent studies have suggested that higher-potency MS drugs (e.g. Tysabri, Ocrevus, Kesimpta) may reduce the risk of a person developing PIRA (Spelman and colleagues. ECTRIMS 2024;P842). And several new medications are now being investigated that may directly target PIRA.
Since it is important to determine if there is evidence of PIRA, is it being adequately investigated? The answer to that question depends on who you ask. A recent survey asked neurologists and people with MS about how disability is assessed in the clinic. The results were presented at the recent Americas Committee for Treatment and Research in MS (ACTRIMS) Forum meeting (Greenberg and colleagues. ACTRIMS Forum 2025;V067).
The survey found a disconnect between what neurologists and people with MS think about the clinic visit. To evaluate PIRA, 40% of doctors said they are being more thorough in their neurological assessment, 52% said they were spending more time with each patient, and 46% said they were seeing people more often. These percentages did not match up with the views of people with MS. Overall, only 19% said their neuro exam was more thorough, 12% said their doctor was taking more time, and 15% said they were seeing their doctor more often. These results suggest that people are not aware of what is being assessed, or doctors are overestimating how thoroughly they are evaluating people.
One thing that both groups agreed on. The typical disability assessment is conducted in less than half an hour: 76% of doctors and 67% of people with MS agreed with this statement. While a majority of doctors said it was important to evaluate PIRA, many said there was not enough time, their methods for detecting PIRA were inadequate, and they lacked treatments to fully address the problem of worsening disability. This situation may change once PIRA is more widely understood and new medications become available.
Share this article
Facebook Twitter pin it! Email
Related Posts
Back
