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Safety of Toll-like receptor 9 agonists: a systematic review and meta-analysis.
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- Author(s): Qin, Mei; Li, Yong; Yang, Xu; Wu, HongQuan
- Source:
Immunopharmacology & Immunotoxicology; Aug2014, Vol. 36 Issue 4, p251-260, 10p- Subject Terms:
- Source:
- Additional Information
- Abstract: Context: 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: 1.11-1.21), leukopenia (RR 1.16, 95% CI: 1.11-1.22), lymphopenia (RR 1.17, 95% CI: 1.10-1.25), thrombocytopenia (RR 1.20, 95% CI: 1.14-1.27), flu-like symptoms (RR 10.59, 95% CI: 3.66-30.66), diarrhea (RR 1.40, 95% CI: 1.18-1.67) and headache (RR 1.61, 95% CI: 1.26-2.06). Injection-site reactions, such as erythema, pain, pruritus and swelling, were mild to moderate. TLR9 agonist therapies have not been associated with clinically significant autoimmune diseases, and few deaths potentially attributable to TLR9 agonists have been reported. Conclusion: The toxicity of TLR9 agonists is generally acceptable, except when the agonist is combined with immunosuppressive agents in patients with advanced non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Immunopharmacology & Immunotoxicology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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