Table 3. Logistic regression modeling the relationship between drug-related and patient-related characteristics and the reporting of late-onset immune-related adverse event(s) with immune checkpoint inhibitors in VigiBase.
| Characteristics (independent variables) | Reporting of late-onset irAE(s) with ICIs (dependent variable) | |||
| Forward stepwise modelROR (95% CI) | P value* | Multivariable modelROR (95% CI) | P value | |
| Sex (female vs male)† | 1.00 (0.66 to 1.04) | 0.105 | 0.94 (0.72 to 1.22) | 0.644 |
| Age (continuous) | 1.00 (0.99 to 1.02) | 0.434 | – | – |
| CTLA4 monotherapy (yes vs no) | 1.60 (0.99 to 2.60) | 0.057 | – | – |
| PD-1/PD-L1 monotherapy (yes vs no) | 1.34 (1.03 to 1.74) | 0.031 | 1.40 (0.74 to 2.62) | 0.300 |
| Combination therapy (yes vs no) | 0.51 (0.38 to 0.69) | <0.0001 | 2.33 (1.19 to 4.57) | 0.014 |
| Duration of ICI treatment (continuous) | 1.001 (1.000 to 1.002) | 0.023 | 0.992 (0.990 to 0.993) | <0.0001 |
| Multiple irAEs (yes vs no) | 0.41 (0.32 to 0.53) | <0.0001 | 3.96 (2.85 to 5.52) | <0.0001 |
| Blood toxicity (yes vs no) | 0.85 (0.34 to 2.12) | 0.725 | – | – |
| Cardiac toxicity (yes vs no) | 1.88 (0.96 to 3.68) | 0.066 | – | – |
| Endocrine toxicity (yes vs no) | 0.70 (0.54 to 0.89) | 0.004 | 1.26 (0.92 to 1.71) | 0.145 |
| Eye toxicity (yes vs no) | 0.57 (0.28 to 1.14) | 0.110 | – | – |
| Gastrointestinal toxicity (yes vs no) | 0.83 (0.64 to 1.07) | 0.154 | – | – |
| Hepatic toxicity (yes vs no) | 1.11 (0.75 to 1.63) | 0.602 | – | – |
| Immune toxicity (yes vs no) | 1.14 (0.42 to 3.14) | 0.798 | – | – |
| Musculoskeletal toxicity (yes vs no) | 1.06 (0.67 to 1.69) | 0.793 | – | – |
| Neurologic toxicity (yes vs no) | 0.87 (0.58 to 1.29) | 0.476 | – | – |
| Renal toxicity (yes vs no) | 1.00 (0.53 to 1.92) | 0.994 | – | – |
| Respiratory toxicity (yes vs no) | 1.25 (0.96 to 1.63) | 0.093 | – | – |
| Skin toxicity (yes vs no) | 0.57 (0.42 to 0.79) | 0.0007 | 1.83 (1.24 to 2.71) | 0.002 |
| Vascular toxicity (yes vs no) | 0.47 (0.20 to 1.11) | 0.085 | – | – |
| Lung cancer (yes vs no) | 1.61 (1.27 to 2.05) | <0.0001 | 0.85 (0.60 to 1.21) | 0.360 |
| Melanoma (yes vs no) | 0.57 (0.46 to 0.71) | <0.0001 | 1.47 (1.04 to 2.06) | 0.027 |
| Reporting of early irAEs (yes vs no) | 15.14 (10.76 to 21.30) | <0.0001 | 0.02 (0.01 to 0.03) | <0.0001 |
*
Variables with a p value <0.05 from the forward stepwise regression approach were included in the multivariable logistic regression analysis.
†
Patient’s sex was included as covariate in the multivariable regression model to assess its interaction with specific ICI organ toxicities.
CTLA4, cytotoxic T-lymphocyte-associated protein 4; ICI, immune checkpoint inhibitor; irAEs, immune-related adverse events; PD-1/PD-L1, programmed cell death protein 1/programmed cell death ligand 1ROR, reporting OR