Late 30s Could Be 'Critical Time' for Starting MS Therapy

Damian McNamara

October 02, 2019

STOCKHOLM ― Until their mid to late 30s, some people with multiple sclerosis (MS) can better compensate for damage to their central nervous system, new evidence suggests. Thereafter, at about age 40, the risk for disability progression ramps up considerably.

These two findings, which emerged from a study of more than 5000 people with MS in Switzerland, carry implications for research as well as for the timing of initiation of disease modifying therapy (DMT), investigators note.

"The age between 37 and 40 seems critical with regard to the compensation of the central nervous system damage caused by MS," Viktor von Wyl, PhD, of the Department of Epidemiology, Institute for Epidemiologie, Biostatistics and Prevention at the University of Zurich, said here at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019.

After controlling for important clinical disease characteristics, von Wyl and colleagues observed a higher risk for first-event disability progression after the fourth decade. "It's not that DMTs are ineffective but that the risk [for progression of disability] drastically increases," he said.

The Bigger Picture

Previous researchers tended to study either pediatric populations with MS ― for whom the risk for relapse is higher despite an overall slower rate of worsening disability ― or adults.

"Most studies have looked at primarily two age groups, but we know it is probably more complicated," von Wyl said. Instead, he and fellow investigators studied a continuous course of MS with respect to age at onset and initiation of immunomodulator therapy.

To do this, they assessed anonymized data from the Swiss Association for the Joint Tasks of Health Insurers database. From this database, the investigatars used data for 14,718 patients who started their first DMT between 1995 and 2017. Of the cohort, 69% were women, the mean age was 39 years, and the mean disease duration was almost 7 years. A total of 85% had relapsing-remitting MS, and the remainder had clinically isolated syndrome.

In an analysis of a subgroup of 9705 people with MS, the median age at the time of disease onset was 32 years, and the median age at the time of initiation of DMT was 37 years. Median follow-up was 6.5 years.

The researchers defined disability according to Expanded Disability Status Scale (EDSS) values. Disability progression was defined as a 1-point increase in EDSS from baseline since initiation of DMT.

Progression and Relapse

With regard to EDSS progression by age of MS onset, a sigmoid-shaped curve emerged from the data: progression hazards remained stable from early childhood to about age 32 years, increased sharply around age 45 years, and then leveled off.

In contrast, when the investigators assessed risk for relapse by age at onset of MS, an almost linear relationship emerged. They found the risk for relapse was highest among younger people with MS and decreased continuously to about age 35 years.

As an example, in an adjusted analysis, the investigators found that a patient who experienced his or her first MS symptoms at age 20 years had a 1.5 times higher risk for relapse while undergoing DMT compared to a 38-year-old. After age 45, the relapse hazard continued to decrease in a linear fashion.

"Ultimately, this is the most relevant clinical question," von Wyl said: "Can we shift the high-risk phase for progression later through the use of highly efficacious treatment?"

To investigate this, the researchers compared outcomes between platform therapies and newer DMTs. The platform therapies included interferon-beta and glatiramer acetate, which 80% of participants were taking. The highly efficacious DMTs included fingolimod, teriflunomide, dimethyl fumarate, and natalizumab.

The question may remain unanswered for now, however. The hazard curve for confirmed disability progression "goes up higher for highly efficacious DMTs," von Wyl said, "probably due to outliers." Therefore, their secondary analysis was "not entirely conclusive." He added, "I wouldn't close the door ― we are limited by sample size."

The investigators also found no statistical difference in relapse risk between therapy types.

The study findings carry implications for future clinical trials, von Wyl said. He suggested that researchers consider the life course of patients with MS and not just pediatric or adult populations.

Interesting and Important

"It is an interesting study," session co-chair Tjalf Ziemssen, MD, PhD, director of the Center of Clinical Neuroscience at the Carl Gustav Carus University Hospital in Dresden, Germany, told Medscape Medical News when asked to comment.

"It's important to collect these data," he added. He said he wished to reserve further comment because he wanted to get a better understanding of the methods.

von Wyl has disclosed no relevant financial relationships. Ziemssen has received personal compensation from Almirall, Biogen, Bayer, Celgene, Novartis, Roche, Sanofi, and Teva for consulting and speaking services, is a section editor for BMC Neurology, and received financial support for research activities from BAT, Biogen Novartis, Teva, and Sanofi.

35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019: Abstract 302, Presented September 13, 2019.

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