Table 2.
Reports of cardiovascular adverse events from ICIs in a pharmacovigilance study
| Reported drug-related adverse effect | Among immunotherapy reports (IMU; n: 31, 321) |
Among FULL database reports (n: 12, 455, 401) | PD1 vs. CTLA4 ROR and 95% CI | COMB vs. MONO ROR and 95% CI | IMU vs. FULL database ROR and 95% CI | ||
|---|---|---|---|---|---|---|---|
| MONO (n: 28, 909) |
COMB (n: 2, 412) | ||||||
| MONO-PD1 (n: 20, 643) | MONO-CTLA4 (n: 8, 266) | ||||||
| Myocarditis | 84 (0.41%) | 6 (0.07%) | 32 (1.3%) | 4, 454 (0.04%) | 5.62 [2.46-12.88] | 4.31 [2.86-6.38] | 11.21 [9.36-13.43] |
| Pericardial diseases | 74 (0.36%) | 13 (0.16%) | 8 (0.33%) | 10, 009 (0.08%) | 2.28 [1.27-4.12] | 1.1 [0.53-2.24] | 3.8 [3.08-4.62] |
| Vasculitis | 56 (0.27%) | 18 (0.22%) | 8 (0.33%) | 20, 987 (0.2%) | 1.25 [0.73-2.12] | 1.3 [0.62-2.67] | 1.56 [1.25-1.94] |
| Reports within vasculitis | |||||||
| Temporal arteritis | 7 (0.03%) | 10 (0.12%) | 1 (0.04%) | 568 (<0.01%) | 0.28 [0.11-0.74] | 0.71 [0.07-3.94] | 12.99 [8.12-20.77] |
| Polymyalgia rheumatica | 14 (0.07%) | 1 (0.01%) | 1 (0.04%) | 1254 (0.01%) | 5.61 [0.74-42.66] | 0.8 [0.08-4.62] | 5.13 [3.13-8.40] |
A recent study of 12 455 401 individual drug case safety reports (ICSRs) in the World Health Organization’s (WHO) VigiBase pharmacovigilance database found higher reporting of cardiovascular adverse events in users of ICIs compared with the full database. This table displays the reporting odds ratios (ROR) and 95% confidence intervals (CI), comparing selected cardiovascular adverse events in overall immunotherapy (IMU) vs. full database (FULL); combined immunotherapy (COMB) vs. mono-immunotherapy (MONO); mono-immunotherapy with anti-PD-1/PD-L1 (PD1) vs. mono-immunotherapy with anti-CTLA-4 (CTLA4) from VigiBase (time period: January 2008 to January 2018). Significant over-reporting is in marked in bold font, after Bonferroni adjustment for multiple tests within immunotherapy subgroups (p≤0.05/10 tests), which is P≤0.005). First reports of ICSRs associated with ICI started in 2008. Note that the database is a database of reports of adverse events from any system from any drug, not limited to ICIs. As this is a drug case safety report database, the database is not reflective of the general population. Modified with permission (Data from Salem, 2018).
Overall immunotherapy (IMU): Any individual case safety report related to nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, ipilimumab or tremelimumab.
Mono-immunotherapy (MONO): Any individual case safety report related to any of the following seven drugs only when used alone (monotherapy): • Anti-PD-1/PD-L1 monotherapy: any of nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab used alone (MONO-PD1) • Anti-CTLA-4 monotherapy: ipilimumab or tremelimumab alone (MONO-CTLA4) • Combination immunotherapy (COMB): Any individual case safety report related to at least one drug from anti-PD-1/PD-L1 inhibitors combined to an anti-CTLA-4. ICSRs, individual case safety reports.