Table 4. Ranking of the Probability of Being the Best Treatment Regimen, by System or Organ Immune-Related Adverse Eventsa.
| System or Organ Immune-Related Adverse Event | Treatment regimen, median rank (95% CrI)b | |||||||
|---|---|---|---|---|---|---|---|---|
| Chemotherapyc | Ipilimumab | Pembrolizumab, 10 mg/kg, every 2 wk | Nivolumab, 1 mg/kg, every 3 wk and ipilimumab, 3 mg/kg, every 3 wk | Nivolumab, 3 mg/kg, every 2 wk | Pembrolizumab | |||
| 3 mg/kg every 3 wk | 10 mg/kg every 3 wk | 10 mg/kg every 3 wk | 2 mg/kg every 3 wk | |||||
| Dermatologic irAEs | ||||||||
| Pruritus | 1 (1-2) | 5 (3-8) | 6 (2-8) | 5 (1-8) | 6 (2-8) | 2 (2-6) | 6 (2-8) | 6 (2-8) |
| Rash | 1 (1-3) | 6 (3-7) | 4 (2-8) | 6 (1-8) | 8 (2-8) | 4 (2-8) | 4 (2-8) | 4 (1-8) |
| Vitiligo | 1 (1-4) | 3 (1-6) | 3 (1-8) | 7 (2-8) | 4 (1-8) | 5 (2-8) | 7 (3-8) | 6 (1-8) |
| Gastrointestinal irAEs | ||||||||
| Diarrhea | 2 (1-5) | 6 (4-7) | 7 (5-8) | 5 (1-7) | 8 (6-8) | 2 (1-5) | 4 (1-6) | 3 (1-7) |
| Colitis | 1 (1-6) | 6 (4-7) | 5 (3-7) | 3 (1-6) | 7 (4-7) | 2 (1-6) | 4 (1-7) | NAd |
| Endocrine irAEs | ||||||||
| Hypothyroidism | 1 (1-3) | 2 (1-5) | 3 (2-7) | 7 (3-8) | 5 (2-8) | 4 (2-8) | 7 (3-8) | 7 (2-8) |
| Hypophysis | NAd | 4 (3-6) | 4 (2-6) | 2 (1-5) | 6 (3-6) | 2 (1-4) | 3 (1-6) | NAd |
| Liver irAEs | ||||||||
| Increased ALT level | 1 (1-4) | 2 (1-3) | 4 (3-5) | NAd | 5 (2-5) | 3 (1-4) | NAd | NAd |
| Increased AST level | 1 (1-4) | 2 (1-3) | 4 (3-5) | NAd | 4 (2-5) | 3 (1-4) | NAd | NAd |
| Hepatitis | NAd | 2 (1-4) | 4 (1-4) | 2 (1-4) | NAd | NAd | 3 (1-4) | NAd |
| Pulmonary irAEs | ||||||||
| Pneumonitis | 1 (1-6) | 3 (1-5) | 7 (2-7) | 3 (1-7) | 5 (2-7) | 3 (1-6) | 6 (2-7) | NAd |
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CrI, credible interval; irAE, immune-related adverse event; NA, not applicable.
We ranked this probability by estimating the median (95% CrIs) of the posterior distribution for the rank of each treatment regimen. Some median ranks across different treatment regimens were the same because rank was an integer. The best treatment regimen was the one with the lowest risk of any irAE.
Median rank refers to the median and the 95% CrI refers to the 95% CrI of the posterior distribution for the rank of each treatment regimen.
Immune-related AEs were the outcomes associated with immune checkpoint inhibitors, not chemotherapy drugs (ie, carboplatin, dacarbazine, and paclitaxel). For chemotherapy users, the adverse events identified were associated with chemotherapy.
No specific individual irAE was reported in that treatment regimen in the included studies, so the indirect evidence could not be generated. For example, pneumonitis was not reported in any included studies comparing pembrolizumab, 2 mg/kg, every 3 weeks with other treatments, so the indirect evidence of pneumonitis from pembrolizumab, 2 mg/kg, every 3 weeks could not be generated by linking that regimen with other treatments.