Myasthenia Gravis Prevalence Increasing, Linked to Hepatitis B Virus in Taiwan

The changing epidemiology of generalized myasthenia gravis (gMG) in Taiwan, especially the increasing prevalence, purported links to older age, and resultant high disease burden and health care costs, have experts calling for ongoing risk assessment and investigation of risk-mitigation strategies.¹

Study authors also highlight the high hepatitis B virus (HBV) infection rates in some Asian countries and its resultant impact on patient outcomes, chronic immunosuppression and increased risk of virus reactivation—which collectively represent “a previously underappreciated risk for patients with gMG receiving immunosuppressants.”

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Data for their population-based retrospective cohort study came from the Taiwan National Healthcare Insurance Research Database (NHIRD), a claims database of population-level data meant to support clinical decisions and health care policy-making,² and the Taiwan National Death Registry.

“The epidemiology of MG in Asian countries/regions is not well understood,” the study investigators wrote in Frontiers in Neurology. “New treatments for gMG will need health technology assessments supported by reference population-based information about the disease burden.”

Their patient population received an MG diagnosis—ocular or general—between January 1, 2009, and December 31, 2019, as identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes through 2016 and ICD-10-CM codes for later years. For inclusion, patients also had to have evidence of at least 3 outpatient visits or 1 hospital admission claim with an MG diagnosis code in the past year and been treated for MG at all patient visits.

During the 10-year study period, there was a 73% increase in the patient population living with MG (ocular or generalized): from 3647 to 6293, representing a jump in the annual infection rate from 15.80 to 26.67 per 100,000 population and a 1.7-fold increase overall (P < .001). the most common comorbidities reported were hypertension (31.6%-33.78%), type 1 or 2 diabetes (16.62%-21.77%), and malignancies (12.18%-16.66%).

Looking specifically at gMG, this patient population expanded by 67.4% during the study period—from 1576 to 2638—despite this group consistently representing 40% to 43% of patients each year living with MG.

Overall mean (SD) patient age rose each year, starting at 51.63 (17.32) years in 2009 and ending at 55.38 (16.29) in 2019. The older patient population living with gMG also grew. Patients 80 years and older jumped 130% between 2009 (n = 76) and 2019 (n = 175).

“No more than 10% of patients with gMG were < 30 years of age in any study year,” the study authors wrote. “Females exceeded males by approximately 1.3:1.”

When prevalence, incidence, and all-cause fatality were investigated, the following results were seen:

• 64% increase in prevalence of gMG cases
• All-cause fatality consistently ranged between 2.76 and 3.79 per 100 patients in each study year
• gMG incidence rates were consistent, ranging from 2.4 to 3.16 per 100,000 population each year
• gMG incidence
• Prevalence rates among women remained stable until age 30, and among men, age 40
• Prevalence rates were more similar between the sexes until age 60, after which rates were higher in men
• All-cause fatality varied widely throughout the study

The authors’ findings on treatment show that the most common treatment prescribed each year was pyridostigmine (90%)—also the most common first- and second-line treatment, in 82% and 96%, respectively—azathioprine use rose from 44% to 56%, and plasmapheresis was used in approximately 10% of patients each year. Least common treatments administered included methotrexate, rituximab, and intravenous immunoglobulins (< 0.7% each).

Temporal trends were not seen incidence of hepatitis C infection, but for HBV, 147 new cases arose over the course of the study, with 22% of these patients receiving at least 4 weeks of antiviral therapy. Among those who had a history of HBV infection at study initiation (n = 334), 7.2% developed HBV reactivation, defined by the authors as “recommencing antiviral treatment for a diagnosis of HBV infection after discontinuation of treatment for at least 6 months.”

“The increasing prevalence of gMG alongside stable incidence and all-cause fatality is likely to be a function of the aging population and the availability of improved treatments, with more patients with gMG surviving into older age,” the study authors concluded. “HBV infection or reactivation may pose a previously underappreciated risk for patients with gMG receiving immunosuppressants, particularly in countries such as Taiwan where HBV is prevalent. Further assessment of this risk and consideration of measures to reduce the risk of HBV infection/reactivation in patients with gMG is needed.”

Reference

1. Herr KJ, Shen SP, Liu Y, Yang CC, Tang CH. The growing burden of generalized myasthenia gravis: a population-based retrospective cohort study in Taiwan. Front Neurol. Published online June 23, 2023. doi:10.3389/fneur.2023.1203679

2. Hsieh CY, Su CC, Shao SC, et al. Taiwan’s National Healthcare Insurance Research Database: past and future. Clin Epidemiol. 2019;11:349-358. doi:10.2147/CLEP.S196293