Safety of Toll-like receptor 9 agonists: a systematic review and meta-analysis.

AbstractContext: The promising efficacy of Toll-like receptor 9 (TLR9) agonists for use against pathogenic infections, allergies, malignant neoplasms and autoimmunity have been demonstrated well in clinical studies, but the safety of TLR9 agonists is controversial.Objective: In light of the safety concerns, we conducted a systematic review and meta-analysis of clinical studies of TLR9 agonists.Methods: A systematic literature search was conducted. We selected studies in which the subjects were treated with a TLR9 agonist and in which the safety of the TLR9 agonist was monitored. We extracted data on adverse events (AEs) when available. A meta-analysis was performed to determine the commonest and clinical significant AEs observed in the controlled studies.Results: Nine single-arm studies and 12 controlled studies met our selection criteria. Subjects treated with TLR9 agonists were at a higher risk of anemia (risk ratio [RR] 1.04, 95% confidence interval [CI]: 1.02–1.06), neutropenia (RR 1.16, 95% CI: 1.11–...