Reporting of atrial fibrillation with bispecific T-cell engagers in the Food and Drug Administration Adverse Event Reporting System

Objective Bispecific T-cell engager (BiTE) therapies activate cytotoxic T cells and promote cytokine release, potentially increasing the risk of atrial fibrillation (AF). The atrial arrhythmic risk associated with BiTE therapy remains unclear. Methods We analyzed individual case safety reports (ICSRs) from the US Food and Drug Administration Adverse Event Reporting System (FAERS) from the second quarter of 2014 to December 31, 2024. Reporting odds ratios (RORs) with 95% CIs and information components (ICs) with 95% credible intervals (CrIs) were used to assess whether AF was disproportionally reported with BiTE therapy as compared to all other drugs in the FAERS. We also evaluated positive (chimeric antigen receptor T-cell [CAR-T] therapy) and negative (paracetamol) control therapies. Results Analysis of 11,129,381 deduplicated ICSRs identified 14,337 cases involving BiTE therapy as a suspect drug, with 97 (0.68%) reporting AF. A signal for disproportional reporting (SDR) of AF with BiTE therapies was observed (ROR, 1.28 [95% CI, 1.04-1.57]; IC, 0.35 [95% CrI, 0.02-0.60]). Individually, epcoritamab (ROR, 2.95 [95% CI, 2.01-4.18]; IC, 1.50 [95% CrI, 0.91-1.92]) and mosunetuzumab (ROR, 3.88 [95% CI, 1.92-7.01]; IC, 1.76 [95% CrI, 0.74-2.46]) were associated with SDRs. No other BiTE therapy showed an SDR. CAR-T therapy, the positive control, showed an SDR for AF (ROR, 2.40 [95% CI, 2.05-2.79]; IC, 1.24 [95% CrI, 0.99-1.42]). In contrast, the negative control, paracetamol, did not. Conclusion AF appears to be disproportionally reported with BiTE therapy in the FAERS. This association warrants further investigation.