MS Disability Risk May Be Changing Over Time

Year after year, patients diagnosed with multiple sclerosis (MS) had a smaller risk of being disabled, a retrospective cohort study in Sweden showed.

Relapsing onset MS patients took longer to reach disability milestones each year they were diagnosed from 1995 to 2010, reported Jan Hillert, MD, PhD, of the Karolinska Institutet in Stockholm, and colleagues, in JAMA Neurology.

“This change in the course of MS is dramatic,” Hillert told MedPage Today. “We cannot prove that it is due to MS treatments, but we have tried our best to correct for other factors and applied the best statistical tests we can and the change is very clear.”

“Such a change has not been described before, and the fact that data come from a registry with high population coverage make the results likely to be correct,” he added.

Randomized, controlled trials of relapsing onset MS have shown that in placebo groups, annualized relapse rates and disability have declined in the past 2 decades, but this may be a function of the short periods assessed in trials or the characteristics of patients selected. Two natural history studies have reported no change in MS disability profiles over time, but these were conducted on populations that largely were untreated. Several extension studies of disease-modifying therapies (DMTs) have suggested that glatiramer acetate (Copaxone) or interferon beta-1a (Rebif) use also may minimize disability.

For this study, Hillert and colleagues analyzed prospectively collected data from the Swedish MS Registry, a nationwide register that collects information from every MS clinic in Sweden, a country with a high prevalence and incidence of MS. They selected a retrospective cohort of 7,331 patients who were diagnosed from 1995 to 2010, following patients for at least 7 years, until April 2017.

Disability scores were measured by the Extended Disability Status Score Scale (EDSS), a measurement of disability on a 0 (no disability) to 10 (death due to MS) scale in 0.5-unit increments. To analyze disability trends, researchers used the following EDSS milestones:

• EDSS 3.0: moderate disability, but no impairment in walking
• EDSS 4.0: significant disability, but able to walk without aid or rest for 500 m (about 1,640 ft)
• EDSS 6.0: requires unilateral assistance to walk about 100 m (about 328 ft) with or without resting

Most patients in the cohort were women (71%) and 91.5% had relapsing onset MS. Their mean age at MS onset was about 34 years and mean age at diagnosis was 38. They had an average of 8.2 recorded EDSS scores.

The researchers excluded any relapse-related EDSS from their analyses. Adjusting for sex, number of clinic visits, diagnostic delays, and onset age, patients with relapsing-onset MS showed:

• A 3% decrease per calendar year of diagnosis for the risk of sustained EDSS 3.0 (HR 0.97, 95% CI 0.96-0.97)
• A 6% decrease for the risk of EDSS 4.0 (HR 0.94, 95% CI 0.93-0.95)
• A 7% decrease for the risk of EDSS 6.0 (HR 0.93, 95% CI 0.91-0.94)

Trends were not significant for patients with progressive-onset MS, which may be due to several reasons, the researchers noted, including the lack of effective DMTs for progressive-onset disease.

“This study contributes to the growing body of evidence that shows that the course of MS has been becoming milder over the last 2 decades,” observed Tomas Kalincik, MD, PhD, of the University of Melbourne in Australia, who was not involved in the study.

“This long-term shift probably results from a combination of two factors: access to more potent therapies early in the disease and a shift in the diagnostic criteria that allows clinicians to diagnose patients with increasingly milder MS forms,” Kalincik told MedPage Today.

“These studies mean good news for patients with MS and their neurologists,” he added. “In fact, specialists who have been treating patients with MS for a long time have seen the change in the waiting rooms of their clinics: their patients now live with less disability and more independently compared to how they lived 2 decades ago.”

The researchers noted several study limitations. An estimated 20% of cases of MS are not registered in Sweden, and it’s unknown whether the same pattern of disability exists in this subpopulation. The authors also could not explore changes in disease progression before 1995.

While the researchers accounted for interval censoring, it’s possible that the right-censoring of patients diagnosed recently (who may not have had time to reach disability milestones) and left-censoring of patients who entered the registry after they reached milestones may have influenced results.