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. 2026 Jan;40(1):e70072.
doi: 10.1111/fcp.70072.

JAK Inhibitors and Memory Impairment: Disproportionality Analyses in the WHO Global Pharmacovigilance Database, VigiBase

Marilou Duboëlle  1 , Adriano Lercara  2 , Yves-Marie Pers  2 , Céline Michel  3 , Marion Lepelley  4 , Marie-Blanche Valnet-Rabier  5 , Jean-Luc Faillie  6 , Virginie Bres  1 , Pascale Palassin  1
Affiliations

JAK Inhibitors and Memory Impairment: Disproportionality Analyses in the WHO Global Pharmacovigilance Database, VigiBase

Marilou Duboëlle et al. Fundam Clin Pharmacol. 2026 Jan.

Abstract

Background: Chronic inflammation is involved in various mechanisms of memory impairment (MI). Although Janus kinase inhibitors (JAKi), which inhibit cytokine-induced JAK-STAT pathway, could theoretically protect against MI, we faced an unexpected case of MI in a non-elderly patient treated with JAKi.

Objective: Our study aims to investigate the association between JAKi and MI.

Methods: We searched VigiBase, the global pharmacovigilance database, for MI cases reported with JAKi from January 2011 to December 2023 and reviewed the literature for additional cases. The potential association was further explored through disproportionality analyses by calculating Reporting Odds Ratios (ROR), with statistical significance defined as a ROR and its 95% confidence interval exceeding 1.

Results: A total of 3788 MI cases associated with JAKi were included, 36.3% of which were serious. Over half involved non-elderly patients, and co-reported confounding drugs were rare. According to disproportionality analyses, MI was reported nearly three times more frequently with JAKi than with all other drugs (ROR 2.92; 95% CI: 2.83-3.01). To illustrate, a 54-year-old woman with rheumatoid arthritis treated with tofacitinib for 6 months experienced MI with word-finding difficulties (e.g., reduced categorical fluency: 25 animals named in 2 min; norm 30-47) and short-term memory loss, fully resolved 6 weeks post-discontinuation.

Conclusion: Our data support the positive association between MI and JAKi, potentially mediated through hippocampal JAK/STAT pathway inhibition, impairing cholinergic neurotransmission and synaptic plasticity. While further investigations are warranted to confirm or refute this pharmacovigilance signal, clinicians should remain vigilant given this potentially serious adverse effect.

Keywords: JAK inhibitor; adverse drug reaction; memory impairment; pharmacovigilance.

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Conflict of interest statement

Yves‐Marie Pers received speaking fees and/or honoraria for advisory board (less than $10 000 each) from Abbvie, Medac, UCB and Novartis. All remaining authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram of the selection of outcome terms. aOne ICSR corresponds to one patient. A patient may have experienced one or more adverse events. bTable S1 details of the excluded co‐reported PTs. HLT: High Level Term of the MedDRA classification; MedDRA: Medical Dictionary for Regulatory Activities; PT: Preferred Term of the MedDRA classification.
FIGURE 2
FIGURE 2
Disproportionality analyses of MI reports (reporting odds ratios) based on VigiBase data. Forest‐plot illustrating disproportionality analyses of MI cases. *DMARDs excluding tofacitinib, the only JAKi classified as a DMARD. JAKi for rheumatologic indications: tofacitinib, upadacitinib, baricitinib and filgotinib. BZD: benzodiazepines; DMARDs: disease‐modifying antirheumatic drugs; HP: healthcare professional; JAKi: JAK inhibitors; MTX: methotrexate; TNFαi: TNFα inhibitors.
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References

    1. Philips R. L., Wang Y., Cheon H., et al., “The JAK‐STAT Pathway at 30: Much Learned, Much More to Do,” Cell 185, no. 21 (2022): 3857–3876, 10.1016/j.cell.2022.09.023. - DOI - PMC - PubMed
    1. Xin P., Xu X., Deng C., et al., “The Role of JAK/STAT Signaling Pathway and Its Inhibitors in Diseases,” International Immunopharmacology 80 (2020): 106210, 10.1016/j.intimp.2020.106210. - DOI - PubMed
    1. Schindler C., Shuai K., Prezioso V. R., and Darnell J. E., “Interferon‐Dependent Tyrosine Phosphorylation of a Latent Cytoplasmic Transcription Factor,” Science 257, no. 5071 (1992): 809–813, 10.1126/science.1496401. - DOI - PubMed
    1. Horvath C. M. and Darnell J. E., “The State of the STATs: Recent Developments in the Study of Signal Transduction to the Nucleus,” Current Opinion in Cell Biology 9, no. 2 (1997): 233–239, 10.1016/S0955-0674(97)80067-1. - DOI - PubMed
    1. Nicolas C. S., Peineau S., Amici M., et al., “The Jak/STAT Pathway Is Involved in Synaptic Plasticity,” Neuron 73, no. 2 (2012): 374–390, 10.1016/j.neuron.2011.11.024. - DOI - PMC - PubMed

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