Multiple Sclerosis (MS) is a disorder of the immune system in which the myelin sheaths of the nerves break and peel off causing the spinal cord.The brain and optic nerve function is impaired, and the patient's neurological disability gradually worsens after the onset of the disease for a decade or two, and the patient will lose the ability to take care of themselves.Blindness and even loss of life.MS is a rare disease, mostly in the young and middle-aged group of 20-40 years old, and because about three-quarters of MS patients worldwide are female, they are also called "beauty disease" by some media.
Well-known MS sufferers, such as the famous cellist Jacqueline Du Pree of the last century, who suffered from MS at the age of 28 and died young at the age of 42, were later filmed as "She is Lonelier than Fireworks."Alice Sara Ott, a 30-year-old German-Japanese pianist, also made public earlier this year.
Left: Alice Sara Ott Right: Du Pree
The Global Burden of Disease (GBD) research team at the University of Washington's Institute for Health Metrology and Assessment published a new article in March in Lancet Neurol that systematically analyzed the world between 1990 and 2016.Region.The burden of MS disease among countries, and statistics of the prevalence and incidence in various regions of the world.In 2016, there were about 2.3 million MS cases worldwide, and the corresponding age-standardized prevalence increased by 10.4% since 1990.Globally, age-standardized mortality rates declined by 11.5%, age-standardized disability-adjusted life years (DALYs) changed little (– 4.2%, – 16 · 4 to 0 · 8), and years of life lost due to premature death (YLLs) reached their maximum in the sixth decade of life.The GBD report notes that MS prevalence has increased substantially in many regions over the last 20 years, in part because of the substantial increase in survival rates.The highest burden of MS disease worldwide is in areas with high prevalence of MS, that is, some developed countries in Europe and America, which is also due to the lack of capacity to diagnose and treat MS in underdeveloped areas (1).
Before the publication of the latest GBD report, the only worldwide epidemiological statistics of MS were derived from the MS International Federation (MSIF) (2).The Institute included MS Global Epidemiology Atlas in 2008 and 2013, but the MSIF data did not use a systematic modeling approach to estimate disease incidence.Mortality and risk factors.Another big problem is that only a handful of countries have completed MS epidemiological surveys and lack ethnically disaggregated epidemiological data.The systematic analysis method of GBD quantifies health loss in detail according to demographic variables and geographical location.Incidence.Response and mortality rates.但唯一问题是由于使用的人群数据分散庞大，统计建模出的数据不确定性区间往往很大.
Among all regions, the age-standardized prevalence of MS increased the most in East Asia and Canada between 1990 and 2016, with growth rates of 44.8% and 81.9%, respectively.The greatest change in prevalence growth between 1990 and 2016 occurred in the SDI (which includes per capita income.For the middle quintile of years of schooling and fertility, or countries with moderate levels of development, the model estimates a 41.3 percent growth rate for this segment of the country.Mortality was reduced by 11.5% worldwide, with the United States having the highest MS mortality rate of any country: 30.7% .
The sex ratio of global prevalence of MS showed differences with age (above).Among children in their teens, the prevalence of multiple sclerosis was similar in boys and girls.The curve diverges from puberty, with a higher prevalence in girls than in boys, and this pattern persists until the sixth decade, when the sex ratio (female: male) is 2:1.In the elderly, the prevalence in women continues to climb, but in men it gradually declines.
Major environmental risk factors include geographic latitude (higher incidence in milder climates), which may reflect the extent of sunlight exposure affecting vitamin D levels or also affecting pathogens prevalent in this area, although genetics may also play a role (3).A second latitude-related risk factor was also validated in models of GBD: each degree increase in latitude was associated with a 1.03-fold increase in MS prevalence (1).
MS prevalence map : It can be seen that as latitude increases, MS prevalence also tends to increase
The analysis results of GBD showed that the prevalence in mainland China and Taiwan increased by 45.6% and 49.5%, respectively, between 1990 and 2016, which were the two regions with the highest increase in prevalence throughout East Asia .
In 2016, the MS Research Center of Tehran University in Iran published a systematic review of MS epidemiology across Asia, which included MS epidemiology data from all Asian regions through 2016 and included 6 studies in China up to 2016 (see figure below) .
The results of this study are notable for some differences in sex ratios, which are concentrated in Beijing.Shanghai.The results of studies in specific cities in China, such as Suzhou, showed that the male-to-female sex ratio (female: male) of Chinese cases spanned a wide range, from a minimum of 1.2:1 to a maximum of 9:1, and the overall estimated male-to-female sex ratio (female: male) of Chinese cases was 1.5:1.Meanwhile, the sex ratio of East Asian cases was 3.4:1, and that of other East Asian cases (female: male) was 3.4:1 in Taiwan, 2.1:1 in Japan, 3.2:1 in Hong Kong, and 1.6:1 in Korea.The average age at onset of MS disease over the past 20 years ranged from 46.4 years in 1993 to 32.6 years in 2016, according to a Chinese study.
According to the investigators of one of the studies, among patients with MS, optic-spinal form of multiple sclerosis (OSMS) is more numerous in northern China compared to western countries, and limb weakness at onset is the most common medical symptom in all patients with OSMS and CMS (classic multiple sclerosis) (5).
Although this meta-analysis systematically includes all MS epidemiological studies in Asia, there are still a large number of studies in the region that have not yet begun, so the epidemiological statistics of MS in countries in the pan-Asian region are still very scarce.Another problem with this study is that the quality of the data used in the different studies included was variable, only a small number of cases were identified, diagnostic criteria and methods of publication were not uniform, and was limited by literature published in English only.
In recent years, there have been new advances in MS epidemiological studies in other countries.An ethnic-epidemiological cohort study of MS in Southern California, published in Neurology in 2013, found that African Americans had the highest incidence among all ethnicities (10.2, 95% confidence interval [CI] 8.4 – 12.4.The incidence in African-American women is as high as 14.72 per 100,000 people, much higher than the 9.25 per 100,000 in white women.3.92/100,000 Latinos and 1.77/100,000 Asians (6).Analysis of data from the Danish MS health insurance system found that the incidence of MS in Danish women doubled between 1950 and 2009, whereas the incidence of MS in men did not increase much during this period.Changes in the environment including elevated rates of obesity, an increase in the number of people who smoke, and changes in the frequency of breastfeeding have the potential to cause a rapid increase in the incidence of MS women (1).
Currently FDA-approved drugs for MS are: Ocrevus ® (ocrelizumab).ZINBRYTA ® (daclizumab).Tecfidera ® (dimethyl fumarate).Tysabri ® (natalizumab).Gilenya ® (fingolimod).LEMTRADA ® (alemtuzumab).REBIF ® (interferon beta-1a).Aubagio ® (teriflunomide).In March 2018, Biogen and AbbVie withdrew Zinbryta ® from the global market due to inflammatory encephalitis and other side effects in MS patients in Europe, less than two years after Zinbryta ® was approved by the FDA for the treatment of relapsing MS in the United States.In February 2018, the FDA approved the strength of Glatopa (glatiramer acetate injection) 40 mg, administered three times a week, as a second dose option for relapsing forms of MS.In May of the same year, the FDA approved Gilenya ® (fingolimod) as the first treatment specifically indicated for the treatment of pediatric MS.Two major ongoing Phase III trials include the Novartis Phase III EXPAND trial to evaluate the receptor modulator siponimod in secondary progressive multiple sclerosis (SPMS) and the oral therapy ibudilast (MN-166) developed by MediciNova, both of which published valid results in 2018 [7-8].
In July 2018, the CFDA approved Sanofi's Obazel (teriflunomide tablets) in China in only 58 days, which is the first oral drug approved in China for the treatment of relapsing MS.Sanofi is assisting patients who meet the indications for its treatment, Obarget.After eligible MS patients receive drug assistance, the annual cost of drug treatment can be reduced by more than 40%, and patients with subsistence allowances can even receive free assistance.In March 2019, Merck Serono's Recombinant Human Interferon Beta-1a Injection (Rebif ®) was included in the first batch of 21 rare disease tax relief drugs.
Currently, data from epidemiological studies of MS in China are lacking.In 2018, Chinese Society of Neurology has led the first large-scale investigation on the survival status of MS patients, involving 50 hospitals in 28 provinces and 1362 patients. The report is expected to be released soon.GBD reports the results to the physician.Researchers.The important enlightenment of policy-makers is that the increasing number of MS patients must be taken into account when investigating the demand for medical services. Developing drugs for MS and ensuring the care of rehabilitation and other departments are all important components of comprehensive MS treatment.More accurate for the future.There is a strong need for epidemiological data from more countries with strong estimates of MS disease treatment.
 Wallin MT, Culpepper WJ, Nichols E, et al.Global, Regional, and National Burden of Multiple Sclerosis 1990 – 2016: a systematic analysis for the Global Burden of Disease Study 2016.The Lancet Neurology.2019.18:269-285.
2] MS International Atlas
3] Reich DS, Lucchinetti CF, Calabresi PA.Multiple Sclerosis.The New England Journal of Medicine.2018.378:169-180.
4] Eskandarieh S, Heydarpour P, Minagar A, Pourmand S, Sahraian MA.Multiple Sclerosis Epidemiology in East Asia, South East Asia and South Asia: A Systematic Review.Neuroepidemiology.2016.46:209.
5] Li T, Xiao H, Li S, Du X, Zhou J: Multiple sclerosis: clinical features and MRI findings in northern China.Eur J Med Res 2014.19:20.
6] Langer-Gould A, Brara SM, Beaber BE, Zhang JL.Incidence of multiple sclerosis in multiple racial and ethnic groups.Neurology.2013.80:1734-1739.
7] Kappos L, Bar-Or A, et al.Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomized, phase 3 study.The Lancet.2018.391:1263-1273.
8] MediciNova Announces MN-166 (ibudilast) Demonstrated a 26% Reduction inConfirmed Disability Progress in the SPRINT-MS Phase 2b Trial in ProgressiveMS: Potential Best-in-Disease Drug