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. 2024 Nov 28;15(1):10317.
doi: 10.1038/s41467-024-54097-1.

Myasthenia gravis following statin therapy: evidence from target trial emulation and self-controlled case series study

Wanchun Xu  1 , Vincent Ka Chun Yan  2 , Zhijuan Zhang  1 , Kwun Kei Fung  1 , Koon Ho Chan  3   4 , Kui Kai Lau  3   4 , Celine Sze Ling Chui  5   6   7 , Francisco Tsz Tsun Lai  1   2 , Xue Li  2   3   7 , Esther Wai Yin Chan  2   7   8   9 , Ian Chi Kei Wong  2   7   10   11 , Eric Yuk Fai Wan  12   13   14
Affiliations

Myasthenia gravis following statin therapy: evidence from target trial emulation and self-controlled case series study

Wanchun Xu et al. Nat Commun. .

Abstract

Several international pharmacovigilance agencies have issued warnings regarding the potential risk of myasthenia gravis (MG) following statin therapy. Our study investigated this association using population-based electronic health records in Hong Kong. We conducted a sequence of target trial emulation (TTE) for interpersonal comparison and a self-controlled case series (SCCS) study for intrapersonal comparison. In the TTE for MG onset, the incidence rates (per 100,000 person-years) and adjusted HRs were 51.91(31.80, 84.74)[HR:6.11 (3.73, 10.01)] in month 1, 16.27(9.81, 26.99)[HR:1.92(1.15, 3.19) in months 2-4, and 15.27(9.05, 25.79)[HR:1.80(1.06, 3.04)] in months 5-7. For risk of exacerbation, the adjusted HRs were 10.69(5.48, 20.84) in month 1, 1.50(0.55, 4.06) in months 2-4, and 2.79(1.33, 5.84) in months 5-7. No increased risks were found during the subsequent 18 months. A similar pattern was observed in SCCS analysis. Our findings recommend a minimum monitoring period of approximately six months for MG symptoms for patients starting using statin.

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Conflict of interest statement

Competing interests: E.Y.F.W. has received research grants from the Health Bureau of the Government of the Hong Kong SAR, the Hong Kong Research Grant Council, National Natural Science Foundation of China, outside the submitted work. I.C.K.W. reports research funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, the National Institute for Health Research in England, the European Commission, and the National Health and Medical Research Council in Australia, consulting fees from IQVIA and World Health Organisation, payment for expert testimony for Appeal Court of Hong Kong, outside the submitted work; and is a non-executive director of Jacobson Medical in Hong Kong, Advance Data Analytics for Medical Science (ADAMS) Limited (HK), Asia Medicine Regulatory Affairs (AMERA) Services Limited and OCUS Innovation Limited (HK, Ireland and UK) a former director of Therakind in England, outside of the submitted work; I.C.K.W. reports role as member of Pharmacy and Poisons Board in Hong Kong, the Expert Committee on Clinical Events Assessment Following COVID-19 Immunisation, and the Advisory Panel on COVID-19 Vaccines of the Hong Kong Government, outside the submitted work. C.S.L.C. has received grants from the Health Bureau of the Hong Kong Government, the Hong Kong Research Grants Council, the Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen, and personal fees from Prime Vigilance, outside the submitted work. E.W.Y.C. reports honoraria from the Hospital Authority and grants from the Hong Kong Research Grants Council, the Research Fund Secretariat of the Food and Health Bureau, the National Natural Science Fund of China, the Wellcome Trust, Bayer, Bristol Myers Squibb, Pfizer, Janssen, Amgen, Takeda, RGA Reinsurance Company, AstraZeneca, the Narcotics Division of the Security Bureau of Hong Kong Special Administrative Region, Innovation and Technology Commission of the Government of the Hong Kong Special Administrative Region, Novartis, National Health and Medical Research Council Australia, outside the submitted work. Francisco Tsz Tsun Lai are partially supported by the Laboratory of Data Discovery for Health (D24H) funded by AIR@InnoHK administered by the Innovation and Technology Commission, outside the submitted work. X.L. received research grants from the Research Fund Secretariat of the Health Bureau, Health and Medical Research Fund (HMRF, HKSAR), Health and Medical Research Fund Fellowship Scheme (HMRF Fellowship, HKSAR), Research Grants Council Early Career Scheme (RGC/ECS, HKSAR), Research Grants Council Research Impact Fund (RGC/RIF, HKSAR), Commission grants from Hospital Authority of Hong Kong; educational and investigator initiate research fund from Janssen and Pfizer; internal funding from the University of Hong Kong; consultancy fee from Pfizer, Merck Sharp & Dohme, Open Health; she is also the former non-executive director of ADAMS Limited Hong Kong; all outside the submitted work. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Flowchart of eligible person-trials.
The number of individuals (in the parentheses) do not sum to the total number of unique individuals because some eligible individuals contributed to different arms in different emulated trials.
Fig. 2
Fig. 2. Estimated Hazard ratio (95% CI) of Myasthenia Gravis onset and exacerbation between statin initiators and non-initiators in Intention-to-treat (ITT) analysis and Per-protocol (PP) analysis in subgroup analysis.
The analysis was adjusted for demographic characteristics (sex and age), low-density lipoprotein cholesterol (LDL-C) level, Charlson comorbidity index (CCI), hypertension, diabetes, and Rheumatic/connective tissue disease, and drug history within 1 year before baseline (β-blocker, calcium channel blockers, Aminoglycosides, and Fluoroquinolones). Statistical significance was defined as a two-tailed p-value.
See this image and copyright information in PMC

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