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Observational Study
. 2025 Jan;34(1):e70082.
doi: 10.1002/pds.70082.

Safety Assessment of Influenza Vaccination for Neurological Outcomes Among Older Adults in Japan: A Self-Controlled Case Series Study

Mitsunori Ogawa  1 , Yoshinori Takeuchi  2   3 , Yukino Iida  4   5 , Masao Iwagami  6 , Kohei Uemura  1 , Sachiko Ono  7 , Nobuaki Michihata  8 , Daisuke Koide  9 , Yutaka Matsuyama  3 , Hideo Yasunaga  10
Affiliations
Observational Study

Safety Assessment of Influenza Vaccination for Neurological Outcomes Among Older Adults in Japan: A Self-Controlled Case Series Study

Mitsunori Ogawa et al. Pharmacoepidemiol Drug Saf. 2025 Jan.

Abstract

Purpose: To assess adverse neurological risks following influenza vaccination in older adults.

Methods: Using a linked database of healthcare administrative claims data and vaccination records from an urban city in Japan (April 1, 2014, to March 31, 2020), we conducted an observational study utilizing a self-controlled case series design. We identified individuals aged ≥ 65 years who experienced adverse neurological outcomes, defined as hospitalizations related to epilepsy, paralysis, facial paralysis, neuralgia, neuritis, optic neuritis, migraine, extrapyramidal disorders, Guillain-Barre syndrome, or narcolepsy. We used conditional Poisson regression to analyze within-subject incidence rate ratios, comparing the risk of these outcomes during risk periods following influenza vaccination (0-6 days and 7-29 days after each vaccination) with nonvaccination periods. Our analysis was adjusted for age and season groups as time-varying covariates.

Results: We enrolled 3283 eligible individuals (men: 1643; mean [standard deviation] age: 76 [7.3] years). The incidence rate ratio for the outcome during the risk periods was 0.93 (95% confidence interval, 0.66-1.30) in risk period 1 (0-6 days after vaccination) and 1.14 (0.96-1.35) in risk period 2 (7-29 days after vaccination), respectively.

Conclusions: We found no evidence that the risk of adverse neurological events was increased after influenza vaccination in older adults. These results may help reassure older adults who are hesitant to receive influenza vaccination because of concerns regarding adverse neurological outcomes.

Keywords: neurology; observational study; pharmacoepidemiology; self‐controlled study design; vaccine safety.

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Conflict of interest statement

Y.T. had received consultant fees from Pharmaceuticals and Medical Devices Agency, EPARK Inc. and EPS Corporation. Y.T. has been conducting a collaborative study with Pfizer Inc. which is not related to this study. The remaining authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Graphical representation of the study timeline.
FIGURE 2
FIGURE 2
Flow diagram of participant selection for outcomes based on all neurological diseases.
See this image and copyright information in PMC

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