Objective:

To evaluate whether antibiotics increase the risk of immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs) and to examine the timing of irAEs onset in relation to antibiotic administration.

Key Findings:

• Patients receiving antibiotics had a higher reported frequency of irAEs (OR = 1.17; 95%CI: 1.12–1.23; FDR<0.001), indicating a significant association.
• Strongest associations were found with fluoroquinolones, sulfonamides, penicillin, macrolides, cephalosporins, and monobactams, highlighting the need for careful antibiotic selection.
• Co-reporting of antibiotics was linked to a higher frequency of irAEs in patients on PD-L1 inhibitors (OR = 1.51; 95% CI: 1.39–1.65; FDR<0.001), suggesting a potential interaction.
• Median time to first reported irAE was shorter in the antibiotic group (31 days vs. 42 days, P < 0.001), indicating that antibiotic use may accelerate irAE onset.

Interpretation:

Antibiotic use during ICI therapy is associated with an increased risk and earlier onset of irAEs, particularly in patients receiving PD-1 inhibitors, which may have significant implications for clinical management.

Limitations:

• Inability to determine the temporal sequence of antibiotic and ICI exposure limits causal inference.
• Unmeasured confounding factors may skew results, necessitating cautious interpretation.
• Potential reporting artifacts could affect the reliability of the data.
• Spontaneous reporting data is unsuitable for formal time-to-event analysis, which may obscure true relationships.

Conclusion:

Antibiotic co-reporting during ICI therapy correlates with higher irAE frequency and shorter onset time, warranting further prospective studies to validate these findings and explore the mechanisms involved.