Meta-Analysis of the Risk of Immune-Related Adverse Events With Anticytotoxic T-Lymphocyte-Associated Antigen 4 and Antiprogrammed Death 1 Therapies

Clin Pharmacol Ther. 2018 Feb;103(2):318-331. doi: 10.1002/cpt.633. Epub 2017 Oct 10.

Abstract

We assessed the risks of immune-related adverse events with anticytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and antiprogrammed death 1 (PD1) therapies by meta-analysis. Twenty-one studies including 11,144 patients were found. Anti-CTLA4 therapy was associated with a significantly higher risk of overall immune-related adverse events: diarrhea, immune-related colitis, pruritus, and rash compared to control therapies (relative risk (RR) = 2.43, 2.10, 11.39, 3.88, 3.87, 95% confidence interval (CI) = 1.77-3.34, 1.52-2.45, 6.30-20.59, 2.37-6.37, 2.39-6.27, P < 0.001 for all outcomes). Anti-PD1 therapy was associated with a significantly higher risk of pruritus (RR = 4.01, 95% CI = 1.97 to 8.17, P < 0.001); however, it did not increase the risks of other adverse events. Anti-CTLA4 and anti-PD1 therapies have distinct features of immune-related adverse events. The results of our study would aid the surveillance and management of immune-related adverse events in patients receiving these therapies.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / adverse effects*
  • CTLA-4 Antigen / antagonists & inhibitors*
  • CTLA-4 Antigen / immunology
  • Data Mining / methods
  • Drug-Related Side Effects and Adverse Reactions / diagnosis
  • Drug-Related Side Effects and Adverse Reactions / immunology*
  • Evidence-Based Medicine / methods
  • Female
  • Humans
  • Immunotherapy / adverse effects*
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Patient Safety
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Immunological
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor