Region in Japan sees steady increase in MS prevalence over 20 years

Tokachi, a region in northern Japan, has seen a steady increase in the prevalence or proportion of people in the population living with multiple sclerosis (MS) over the past two decades, a recent study found.

Data show the disease has also become more common in women in northern Japan. In 2021, for every four women with MS in the region, there was one man with the disease — a ratio that grew from 2.6 women to 1 man in 2001.

“Our results demonstrated a consistent increase in the prevalence of MS among the northern Japanese over 20 years, particularly in females,” the researchers wrote, noting that “the female–to–male ratio of MS in the Tokachi area has also been increasing.”

Moreover, over the course of the past 40 years, the incidence of MS, or the number of new cases each year, jumped by nearly eight times, the study found.

The study, “The prevalence and incidence of multiple sclerosis over the past 20 years in northern Japan,” was published in Multiple Sclerosis and Related Disorders.

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MS, a disease that affects the brain and the spinal cord, is unevenly distributed worldwide, with prevalence lower in regions closer to the equator. It also appears to be more common in Western countries than in Asia, though not many studies have been done in that part of the world.

There are many risk factors for MS, and people who move from one place to another may see their risk of developing the disease increase or decrease depending on where they’re from and how long they’re staying in their host country.

Located in Hokkaido, the northernmost of Japan’s main islands, the Tokachi province has a population of about 350,000 people, which has been stable for the past 60 years due to low rates of emigration and immigration.

Given these characteristics, “the Tokachi area is a relatively noise-free locale for conducting epidemiologic” studies examining changes in the frequency of certain diseases over time, the researchers wrote.

Thus, a team in Japan has been conducting surveys in the region since 2001 to examine how MS prevalence and the clinical characteristics of patients with the neurodegenerative disease changed over the years. Surveys were conducted in 2001, 2006, 2011, 2016, and more recently in 2021.

At the time of the last survey, there were 75 MS patients in Tokachi, representing a prevalence of 22.4 patients per 100,000 people.

Their mean age was 47, and they had been living with the disease for a mean of 17.2 years. Most — 62 people or 82% — had relapsing-remitting MS. Less common disease types were secondary progressive MS (15%) and primary progressive MS (3%), which affected two of the patients.

A the time of the survey, seven disease-modifying therapies had been approved in Japan, including interferon-based therapies, Copaxone (glatiramer acetate), Tecfidera (dimethyl fumarate), Gilenya (fingolimod), Mayzent (siponimod), and Tysabri (natalizumab). Most patients (71%) were or had been receiving one of these therapies, and 40% of them had made at least one treatment switch.

The prevalence of MS was higher in women than in men (34.4 vs. 9.3 per 100,000 people), and the female-to-male ratio had grown over the years. For each man with the condition, there were 2.6 women in 2001, 2.8 women in 2006, 3.4 women in 2016, and four women in 2021.

The total number of MS patients in the region also has been increasing. The prevalence of the disease, standardized by the Japanese national population, increased from 6.9 cases per 100,000 people in 2001, to 15.3 cases per 100,000 people in 2011, to 23.3 cases per 100,000 people in 2021.

There was “a steady increase of prevalence of MS in the Tokachi area from 2001 to 2021, and the consistent increase was predominantly among females,” the researchers wrote.

The Tokachi area is a relatively noise-free locale for conducting epidemiologic [studies].

When the researchers looked at how many new cases of MS were diagnosed each year, a measure called incidence, they found that diagnoses increased steadily from 0.09 cases per 100,000 in the period between 1980 and 1984 to 0.99 diagnoses per 100,000 people between 2005 and 2009. Then, incidence rates remained stable until 2019.

Importantly, incidence rates remained fairly stable among men over the past four decades, but increased by nearly eight times in women over the same period of time, the researchers said.

Many people with relapsing-remitting MS go on to develop secondary progressive MS. Among the 75 people in the 2021 survey, 11 had already transitioned to SPMS, which occurred about 17 years after their initial RRMS diagnosis.

“The time course to SPMS here is similar to that in Western countries but it occurs more rarely in Japan,” the team wrote.

Further research is needed to understand why the prevalence and incidence of MS is increasing, particularly among women, they said.

“Although our studies documented increases of the incidence and the prevalence of MS in the Tokachi area, the reasons for the increase have not been clear,” the team wrote.