Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep 21:17:17562864241276204.
doi: 10.1177/17562864241276204. eCollection 2024.

Exploring the association of disease-modifying therapies for multiple sclerosis and BTK inhibitors with epilepsy

Afsaneh Shirani  1 , Nil Saez-Calveras  2   3 , Jack P Antel  4 , Moein Yaqubi  5 , Wayne Moore  6 , Amy L Brewster  7 , Olaf Stuve  8   9   10
Affiliations

Exploring the association of disease-modifying therapies for multiple sclerosis and BTK inhibitors with epilepsy

Afsaneh Shirani et al. Ther Adv Neurol Disord. .

Abstract

Background: Multiple lines of evidence suggest a role of inflammation in epilepsy. Seizure incidence in patients with multiple sclerosis (MS) is twofold to threefold higher than the age-matched general population.

Objectives: To explore the association of MS disease-modifying therapies (DMTs) and FDA-approved Bruton tyrosine kinase inhibitors (for lymphocytic malignancies) with the occurrence of epilepsy using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Design: Secondary analysis of the FAERS database.

Methods: We conducted a disproportionality analysis of FAERS between 2003-Q4 and 2023-Q3. MS DMTs and the Bruton tyrosine kinase inhibitor, ibrutinib, were included in the analysis. An inverse association was defined by a 95% confidence interval (CI) upper limit of reporting odds ratio (ROR) <1.

Results: We found an inverse association of ibrutinib, ocrelizumab, ofatumumab, rituximab, and teriflunomide with epilepsy. The strongest inverse association was seen with ibrutinib (ROR: 0.338; 95% CI: 0.218-0.524).

Conclusion: Our findings suggest the possibility of considering these medications for repurposing opportunities in epilepsy and support a potential pathogenic role of leukocyte subsets in seizure perpetuation.

Keywords: BTK inhibitors; FAERS database; disease-modifying therapies; epilepsy; multiple sclerosis.

Plain language summary

How multiple sclerosis treatments and Bruton tyrosine kinase inhibitors may be linked to epilepsy The research presented in this manuscript attempts to elucidate the potential relationship between inflammation and epilepsy. Multiple sclerosis (MS) is the most common inflammatory disorder of the brain and spinal cord in humans. There are over 20 FDA-approved disease-modifying therapies (DMTs) for MS. Other anti-inflammatory agents called Bruton tyrosine kinase (BTK) inhibitors are in clinical development. We show that the use of some DMTs and a BTK inhibitor appear to be associated with a lower chance of epilepsy.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Disproportionality analysis demonstrating the association between epilepsy and various immunotherapies based on the data from the FDA Adverse Event Reporting System database. The reporting odds ratio indicates the odds of a certain adverse event (in this case, “epilepsy”) occurring with the drug of interest, compared to the odds of the same adverse event occurring with all other drugs in the database. Drugs associated with fewer than five drug-event (drug–epilepsy) pairs, including acalabrutinib, zanubrutinib, and ublituximab, as well as those with no existing reports in the database, including pirtobrutinib, were excluded from the disproportionality analysis.
See this image and copyright information in PMC

References

    1. Thijs RD, Surges R, O’Brien TJ, et al.. Epilepsy in adults. Lancet 2019; 393(10172): 689–701. - PubMed
    1. Wyatt SK, Witt T, Barbaro NM, et al.. Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy. Exp Neurol 2017; 295: 184–193. - PubMed
    1. Sun FJ, Zhang CQ, Chen X, et al.. Downregulation of CD47 and CD200 in patients with focal cortical dysplasia type IIb and tuberous sclerosis complex. J Neuroinflamm 2016; 13(1): 85. - PMC - PubMed
    1. Vezzani A, Balosso S, Ravizza T. Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy. Nat Rev Neurol 2019; 15(8): 459–472. - PubMed
    1. Varvel NH, Neher JJ, Bosch A, et al.. Infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus. Proc Natl Acad Sci U S A 2016; 113(38): E5665–E5674. - PMC - PubMed

LinkOut - more resources