Efficacy of integrative medicine using Yinhua-based herbal granules on herpangina: A Bayesian network meta-analysis of randomized controlled trials

Different Traditional Chinese Medicine (TCM) in the format of granules, such as Kanggan Granules (KangGs), Kouyanqing Granules (KouGs), Lianhua Qingwen Granules (LQGs), Qingkailing Granules (QGs) and Xiao'er Qingjie Granules (XQJGs), collectively named Yinhua-based herbal granules (YH-HGs) have been widely used in the management of pediatric outpatients with herpangina. Few head-to-head randomized controlled trials (RCTs) have compared the efficacy of these agents. This network meta-analysis (NMA) was conducted to indirectly compare the efficacy of YH-HGs. This systematic review and fixed-effect NMA was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) extension statement for NMA. RCTs assessing the efficacy and safety of YH-HGs in children that were also receiving ribavirin as the conventional therapy were searched from eight databases and two trial registers up to Jan 13, 2022. The primary outcome was total effectiveness rate (TER). The secondary outcomes were total adverse events (TAEs) and the time to symptom improvement of fever, vesicles, pain and salivation. Relative risk (RR) and weighted mean difference with 95% confidence intervals (CIs) were estimated by direct pairwise meta-analysis (MA) and NMA. A total of 10 RCTs, enrolling 1 017 pediatric patients, were included. YH-HGs were better than no medication (NM) in TER (RR = 1.22, 95%CIs, 1.16 – 1.28) by direct pairwise MA, in which KangGs (RR = 1.24, 95%CIs, 1.05 – 1.47), KouGs (RR = 1.17, 95%CIs, 1.08 – 1.27), LQGs (RR = 1.24, 95%CIs, 1.14 – 1.35), QGs (RR = 1.33, 95%CIs, 1.11 – 1.58) and XQJGs (RR = 1.18, 95%CIs, 1.00 – 1.40) were also more efficient than NM. As for secondary outcomes, YH-HGs was associated with a 103% increased risk of TAEs compared to NM, but no significant differences were found. YH-HGs has a more positive symptom improvement effect than NM in fever, vesicles, pain and salivation. The ranking results showed that QGs (79.2%) had the highest probability ranking first in TER and KangGs (63.6%) ranked as the second, followed by LQGs (52.4%), XQJGs (50.3%), KouGs (49.7%), and NM (4.9%) at last. Our findings support the better efficacy of YH-HGs than NM as regards TER. QGs, KangGs, LQGs, XQJGs, KouGs remain superior to NM and their clinical choice should depend on the patient's conditions to improve symptoms better for the different effects. Given the limitations of NMA, head-to-head RCTs with high-quality are needed.