Pace of Multiple Sclerosis Progression May Be Slowing

The progression of relapsing-onset multiple sclerosis (MS) and its associated disability may be slowing, results from a large population-based study suggest.

In an evaluation of more than 7000 patients from Sweden, the risk for reaching a sustained score of 6.0 on the Expanded Disability Status Scale (EDSS) dropped a significant 7% per year for the participants diagnosed with relapsing MS between 1995 and 2010.

The score of 6.0 on the EDSS scale reflects patients who need unilateral assistance to walk about 100 meters, with or without resting.

Although there were also significant decreases in risk for reaching other disability milestones, this only applied to the relapsing-onset form of MS. The same positive trends were not observed in patients with progressive-onset MS.

"In my mind, the most likely factor behind this positive development are disease modifying treatments" (DMTs), study coauthor Jan Hillert, MD, PhD, professor and senior physician, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, told Medscape Medical News.

"So my take-home message to fellow MS-treating neurologists would be: Keep up the good work — the treatment we offer is likely to be of major importance for our patients' future!" Hillert said.

The findings were published online March 18 in JAMA Neurology.

Countering Previous Research

Although multiple prior studies have evaluated the natural history of MS, "there are little data on whether the trajectory of the disease has changed over time, as new diagnostic and therapeutics for MS have come into clinical use," the researchers note.

For example, two natural history studies revealed no changes in disability profile among patients with MS over time, which stand in contrast to the current findings.

However, the current investigators note that these studies were "conducted on an essentially untreated population."

To get a more "real-world" sense as to whether the risk for reaching disability milestones has changed over time, the researchers assessed a cohort from the Swedish MS Registry.

Among the 7331 patients with two or more EDSS scores in their records, 71% were women and 92% had relapsing-onset disease. Mean age at MS onset was 34 years, mean age at diagnosis was 38 years, and participants had a mean of 8.2 EDSS scores in the registry. The investigators excluded any EDSS scores taken during relapse.

The mean follow-up time was 8.5 years.

Decreasing Trend

The population-based cohort had a significant 3% decrease in risk per calendar year of diagnosis for reaching an EDSS score of 3.0. Neurologists assign this score to patients with MS who experience moderate disability and who can walk without impairment.

Results also showed a significant 6% decrease per year in risk for attaining an EDSS of 4.0. Patients with this score have significant disability but can walk 500 meters without assistance or rest.

Compared with the patients who reached the EDSS 3.0 and 4.0 score levels, those who reached the more disabled 6.0 score were older at disease onset and at diagnosis, and were more likely to have progressive-onset MS.

In addition, patients who attended more clinic visits, those who were older at onset of relapsing-onset MS, and men had higher risk for attaining any of the disability outcomes in the study.

Interestingly, the participants diagnosed more recently (2005–2010) experienced more average annual relapses during the first 2 and 5 years from MS onset. This group also had a lower rate of recovery from the presenting attack compared with those who were diagnosed earlier (1995–2000).

The investigators adjusted their calculations for sex, age at MS onset, and total number of clinic visits. They also controlled for any confounding associated with newer diagnostic criteria or greater availability of MRI scans in recent years.

Unanswered Questions

The mechanisms behind the positive trend toward slower progression remain unknown, Hillert noted.

"We only studied the trend of risk for reaching disability milestones and can only speculate on the reasons," he said.

The researchers theorize that several factors may be contributors in addition to an increase in availability and effectiveness of DMTs in recent years. Earlier diagnosis and treatment, as well as changes in health behaviors or environmental exposures, could also contribute to the study findings.

"As always, you need to be careful in drawing conclusions from observational data, but the change we see is dramatic and in the expected direction, given the massive investment in MS treatment from society and the healthcare sector," Hillert said.

"Because significant societal resources are presently being invested in MS treatments, our findings suggesting that these medications may affect the long-term course of disease are encouraging," the researchers write.

They add that future studies should seek to identify the underlying reasons for their observations.

More Research Needed

Commenting on the findings for Medscape Medical News, Bruce Bebo, executive vice president of research programs at the National MS Society in New York City, said that this was "a well-done, population-based study by a highly regarded group" who addressed the question of whether the course of MS disability progression has changed over time.

"We are excited about the possibility that the increased availability and use of disease-modifying treatments may be an important contributor to the decrease in risk of disability progression," said Bebo, who was not affiliated with the current study.

"However, other reports have found little to no effects of disease-modifying therapy on the long-term accumulation of disability," he added.

Although the new research "adds to our growing knowledge of the potential benefits" of this type of therapy for MS, "more work remains to be done before we have a definitive answer," Bebo said.

The study was funded by the Swedish Research Council and the Swedish Brain Foundation. Hillert has received honoraria for serving on advisory boards for Biogen, Sanofi Genzyme, and Novartis; has received speaker's fees from Biogen, Novartis, Merck Serono, Bayer Schering, Teva Pharmaceutical Industries, and Sanofi Genzyme; and has served as principal investigator for projects for or has received unrestricted research support from Biogen Idec, Merck Serono, Teva Pharmaceutical Industries, Sanofi Genzyme, and Bayer Schering. Bebo has disclosed no relevant financial relationships.

JAMA Neurol. Published online March 18, 2019. Abstract

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