榴莲视频

PARIS -- The debate over what exactly constitutes "benign" multiple sclerosis still rages, with several presentations here -- each with different methodologies -- coming to markedly different conclusions.

Using a popular definition of an Expanded Disability Status Scale (EDSS) score of 3.5 or lower at 15 years, a prospective British cohort found a prevalence of about 42%, and a Swedish registry study using a similar cutoff found a prevalence of 22% -- both involving mostly untreated patients.

But a Welsh registry study that took into account more than just the EDSS -- including fatigue, depression, and cognition -- put the prevalence far lower, at around 1%. Meanwhile, a U.S. retrospective chart review that included patients treated with disease-modifying therapies counted 31% to still be "benign" at 20 years.

The variance reflects the current wide range reported in the literature, cited across all presentations to be from 6% to 64%.

One thing all the presenters at the joint agreed on, however, is that there does appear to be a certain subset of MS patients who will have much slower and less debilitating disease progression.

"We shouldn't put a label on it," Ali Manouchehrinia, PhD, of the Karolinska Institute, who reported the Swedish data, told 榴莲视频. "The conclusion is that there are a group of patients who progress at a much lower rate. They still progress. They are getting worse. MS has an impact. But it's not as much as it is for the rest."

By the 'Standard' Definition

His study evaluated 11,222 relapsing MS patients in the Swedish National MS Registry, and using a cutoff of an EDSS of 3 or lower found a prevalence of 22% at 15 years that fell to 6% at 25 years.

In further analyses, they found that those without benign MS accumulated an extra 0.2 points on the EDSS per year compared with those with so-called benign MS. By the age of 40, for instance, mean EDSS score in those with benign disease at year 15 was two points lower than in those with non-benign MS.

Cognitive impairment worsened by an extra 0.4 points on the Symbol Digit Modalities Test (SDMT) per year in those without benign disease, so that 10 years into their disease their SDMT scores were 7 points lower than those with benign disease.

Finally, non-benign MS patients had more missed workdays per year than benign MS patients; they also had a 7-fold higher risk of all-cause mortality.

Manouchehrinia said the patients with benign disease were younger at disease onset (age 28 versus 32), slightly more likely to be female (75% versus 70%), had a lower relapse rate within 2 and 5 years of onset, their first relapse was often a sensory relapse, and they were more likely to show complete recovery from their first relapse.

Though benign disease is a "retrospective" diagnosis, he said, further study of these risk factors can help determine which patients will have a less aggressive disease course -- an important consideration in the age of more expensive and more potent medications that come with side effects.

Karen Chung, MBBS, of University College London, who presented the prospective British cohort data, said her results support "the idea a very stable 'benign' MS does exist."

Her team recruited 132 patients who had clinically isolated syndrome (CIS) in 1984-1987 and followed them for a mean of 30 years, for both clinical and MRI outcomes. They excluded CIS patients who never developed MS.

After also excluding those lost to follow-up, they ended up with about 80 patients with known MS; 35 had relapsing MS, 25 had secondary progressive MS, and 16 patients had died with an EDSS of 10, indicating their death had to do with their disease.

Chung and colleagues found that over the 30-year study, 32 people had an EDSS of 3.5 or lower, putting the prevalence at 42%. Only three of these patients used a disease-modifying drug, and they were all first-line injectables, Chung said.

Counting Other Factors

Emma Tallantyre, PhD, of Cardiff University in Wales, said the EDSS is a "blunt tool" for assessing the full impact of MS, and proposed a far more stringent definition of truly benign MS. In addition to an EDSS of 3 or less at 15 years, "benign" patients should have no clinically significant fatigue, depression, bladder symptoms, or cognitive impairment; no impact of MS on occupation; and no exposure to disease-modifying drugs.

By that definition, she found a prevalence of 1% in a Welsh cohort of 222 patients with unlimited walking ability, 56 of whom were assessed and included in the study.

Despite the low numbers, she said researchers and clinicians "shouldn't use the term 'benign MS' readily because it could be dismissive and it isn't representative of what's really going on. EDSS is a blunt tool; cognition and fatigue aren't being detected, but they could cause significant disability."

Andrew Bouley, MD, of Beth Israel Deaconess Medical Center in Boston, and colleagues found that 31% of patients had benign disease defined as EDSS of 3 or less at 20 years -- but about half of their patients were on disease-modifying therapy.

Those with more benign disease, he said, were less likely to be on the more aggressive therapies such as natalizumab, rituximab, and the other chemotherapeutic agents.

"The idea that not all MS is the same isn't new," Bouley said.