Combination tools may be the answer for tracking MS disability


Better clinical tools than the Expanded Disability Status Scale (EDSS) are needed to classify multiple sclerosis (MS) severity and monitor disease progression, according to leading experts.

In a recent narrative review, Bianca Weinstock-Guttman, MD, of the State University of New York at Buffalo and colleagues discussed the shortcomings of the EDSS and explored how emerging approaches could fill these practice gaps.

Dr. Bianca Weinstock-Guttman
“The goal of this review is not a systematic assessment but rather a targeted review of recent literature that focuses on specific endpoints related to MS progression,” the investigators wrote in the International Journal of MS Care. “We highlight general viewpoints from a panel of four experts in MS research ... that convened at the 2019 European Committee for Treatment and Research in Multiple Sclerosis meeting in Stockholm. ... At this meeting, the panel discussed the utility of clinical methods currently used to predict and monitor MS progression and suggested general directions for future studies that may help clinicians effectively monitor MS disease worsening.”

The goal of this review is not a systematic assessment but rather a targeted review of recent literature that focuses on specific endpoints related to MS progression.

Shortcomings of EDSS

Dr. Weinstock-Guttman and colleagues first summarized the limitations of the EDSS, including “lack of accuracy, limited sensitivity to change at certain disability levels of the disease, focus on physical ability, and nonstandardized interpretability,” all of which are supported by “an ample body of evidence.”

“Foremost, the EDSS is meant to function as a measure of irreversible disability in MS; however, the literature shows that it fails to serve this basic purpose,” the investigators wrote.

In support of this statement, they cited a review of 31 randomized clinical trials that showed significant improvements in EDSS among placebo arms. The EDSS may also overestimate accumulation of permanent disability by as much as 30%, and findings can be inconsistent across levels of disease severity, particularly with EDSS scores of 6 and above.

Beyond these issues with inconsistency, the EDSS may skew or fail to detect various elements of disease progression.

“While lower-scale values are influenced by impairments detected by a neurologic examination, values above 4 are mainly based on walking ability, and values above 6 are based on patient handicaps,” the investigators wrote. “The EDSS does not adequately capture the dimensions of cognition, upper extremity function, or fatigue, which are believed to be relevant predictors of long-term disease progression in MS.”

Based on these limitations, Dr. Weinstock-Guttman and colleagues called for improved clinical tools.

“[I]t is the panel’s opinion that alternative measures are needed to better classify disease severity in patients with MS and to assess disease progression,” they wrote.

Image credit: Frédérik Astier/Science Source

Emerging clinical tools

According to the investigators, fatigue and lower limb function should both be considered when evaluating MS. They cited a variety of supportive studies, including one involving older patients, which found a link between these parameters and progression to secondary MS within 5 years. Compared with patients that did not progress, patients that progressed were four times more likely to have fatigue and three times more likely to have reduced lower limb function.

Simple physical tests may also offer insight into disease progression, the investigators suggested, referring to the timed 25-foot-walk test, the low-contrast letter acuity test, and the nine-hole peg test (NHPT). The NHPT is a “gold-standard measure of manual dexterity,” the investigators noted, with the benefit of high interrater and test-retest reliability.

Image credit: Frédérik Astier/Science Source

Ultimately, clinicians may need to combine more than one approach to gain the most clarity, Dr. Weinstein-Guttman and colleagues suggested.

For example, clinicians may consider adding a cognitive assessment, such as the symbol digit modalities test or the brief international cognitive assessment for multiple sclerosis, to one of the above physical tests. MRI findings may also provide insight, as demonstrated by the Rio scoring system, which incorporates MRI lesions, EDSS scores, and presence of relapse.

“Although our current understanding of MS disease progression does not allow for a single most-promising measure to be identified, research should continue to explore promising themes and measures to improve clinical and real-world assessments of MS treatments in the near term,” the investigators wrote.

Image credit: Frédérik Astier/Science Source

Simpler tools may promote usage

Robert Fox, MD, staff neurologist at the Mellen Center for Multiple Sclerosis and vice chair for research at the neurological institute, Cleveland Clinic, agreed with the investigators that the EDSS is a suboptimal clinical tool, when it’s used at all.

“EDSS is a very cumbersome measure,” Dr. Fox said in an interview. “It’s a very time-intensive assessment, and it can only be done by a trained clinician, meaning a neurologist or an advanced practice provider. And that makes it rather cumbersome to implement on a day-to-day basis when managing patients.”

Dr. Robert Fox
EDSS is a very cumbersome measure.

In contrast, newer tests “can be administered by anyone,” Dr. Fox said, making them more attractive for routine use. Beyond the tools described by Dr. Weinstock-Guttman and colleagues, Dr. Fox highlighted ongoing development of self-directed assessments taken on an electronic device.

“Patients can sit in front of an iPad and just administer these tests to themselves with very little input from the provider staff,” Dr. Fox said. “The office staff that provide the supervision can be much more affordable office staff than the neurologist or advanced practice providers. So what we’re doing is we’re making these [tests] more accessible, making it more able for community-based providers to measure these outcomes. And if you make it easier to measure, you’re more likely to implement it in routine clinical care.”

Although the emerging tools have distinct advantages, they still have their own drawbacks and unanswered questions, Dr. Fox said. For example, he noted that a 20% change in NHPT score is considered clinically meaningful, despite a lack of thorough validation. And so, for now, newer tools are more likely to supplement EDSS, instead of replacing it entirely.

“We’re probably not going to abandon the EDSS,” Dr. Fox said. “We have great experience with it. We understand what it means. We have a great historical context. Combination measures are likely going to be an important component of our future measurement of disability.”

The review was supported by Celgene. The investigators disclosed additional relationships with AbbVie, Sanofi, Biogen, and others. Dr. Fox reported no relevant conflicts of interest.