Can disability ever improve?

Three decades ago, a first generation of MS medications was introduced that provided modest benefits in preventing relapses and disability worsening. So modest, in fact, that one treatment (Copaxone or glatiramer acetate) could not demonstrate an impact on disability. Those treatments led to string of more potent medications that were better at preventing disability worsening. Their efficacy begged the question: can disability actually improve with treatment?

And what does disability improvement mean? This requires a bit of explanation.

Neurologists typically assess disability with a tool called the EDSS (for Expanded Disability Status Scale) ( The scale evaluates the type and severity of neurological impairments and is scored from 0 (normal) to 10 (death). The score is not linear, which means that a person with a score of 4 does not have twice the disability of someone with a score of 2. Instead, the scores are descriptive and indicate key milestones, such as requiring a walking aid (EDSS 6) or requiring a wheelchair (EDSS 7). With a score of EDSS 5 or higher, people have some degree of walking impairment. Below EDSS 5, people are fully ambulatory but can have a wide variety of issues (e.g. numbness, muscle weakness, vision problems, etc.).

Disability scores can mean different things. After a relapse, a person will often have disability worsening (e.g. an EDSS score that goes from 2 to 3), meaning that they are more impaired compared to before the relapse. But in many cases, that worsening is temporary – the symptoms improve and the person’s function can fully return. Doctors consider this to be an episode of disability worsening, which is often caused by an inflammatory flare-up. Disability progression is more permanent and is typically caused by tissue damage in the brain and spinal cord. To help differentiate worsening from progression, doctors use a three- or six-month cut-off: if a person’s function worsens and stays at that level for three or six months, it is considered to be true disability progression. So if a person’s EDSS score goes from 2 to 3, and the score is still 3 when the person is examined three months later, that person has (in the language of clinical trials) “three-month confirmed disability progression” (CDP). This isn’t entirely accurate because some people may longer – perhaps a year or more – to recover from a relapse.

In trials of disease-modifying therapies, the proportion of people with three-month CDP on treatment will be somewhere in the neighbourhood of 10-20% (depending on the drug, the study and when it was done). This means that during the two-year study, about 10-20% on treatment experienced at least a 1-point worsening on their EDSS score – which is perhaps 30-40% fewer people when compared to those taking no treatment.

This 10-20% represents people who got worse. A recent trend has been to look at people who got better, i.e. their EDSS score improved (e.g. from 2 to 1). One of the earliest studies that looked at this issue examined people switching from an injectable therapy to Tysabri. It found that 44% showed an improvement in their disability level about 44 weeks after starting Tysabri (Belachew and colleagues. Eur J Neurol 2011;18:240-245). This probably overestimated the benefit since some of the progression was likely to be disability worsening due to relapses.

A better guide has been the Tysabri Observational Program (TOP), which tracks people on Tysabri. TOP has reported that 23.9% of people in the program (about 1 in 4) showed an improvement in their disability level (Wiendl and colleagues. Mult Scler 2021;27:719-728). People in the program were typically taking Tysabri for about three years. About one-half continued to show this improvement eight years later. Other studies have found that individual symptoms, such as hand tremor, can also become less severe after taking Tysabri (Rinker and colleagues. Mult Scler Relat Disord 2014;3:505-512).

Disability has also been shown to improve in some people taking Lemtrada. Over a nine-year period, about 43% had a period of disability improvement at some point – although many lost that gain later on (Hunter and colleagues. Neurol Ther 2021;10:803-818). But early improvement appeared to be a good sign. For most people in this group, their disability level was unchanged at the end of the nine-year period.

Some people taking other high-potency medications, such as Gilenya, Mavenclad, Ocrevus and Kesimpta, have also shown improvement in their level of disability (Cree and colleagues. Mult Scler 2021;27:2219-2231. Giovannoni and colleagues. Adv Ther 2021;38:4975-4985. Hauser and colleagues. N Engl J Med 2017;376:221-234. Hauser and colleagues. N Engl J Med 2020;383:546-557).

These results suggest that controlling inflammation with a high-potency medication may limit the damage caused by a relapse, providing a relapse-free respite during which the body can heal. That may buy some time, slowing the process of nerve damage and enabling people to enjoy more years with less disability.

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