Lin, Shih-YingShih-YingLinHUNG-YING LINSun, Jui-ShengJui-ShengSunJENNY ZWEI-CHIENG CHANG2025-09-232025-09-232025-12https://scholars.lib.ntu.edu.tw/handle/123456789/732276This study evaluates the effectiveness of adjunctive therapies combined with non-surgical periodontal treatment for Stage III/IV Grade C periodontitis, focusing on pocket depth (PD) reduction, clinical attachment level (CAL) gain, and adverse events. A systematic review and network meta-analysis were conducted, including randomized controlled trials up to September 2024. Inconsistencies and publication bias were detected, prompting sensitivity analyses and effectiveness rankings of adjunctive therapies. Data from 50 studies were included, with 45 entered into network meta-analysis, covering 24 interventions and 1431 patients. Compared to scaling and root planing (SRP) alone, adjunctive systemic lincosamides with nitroimidazole (Mac/Linc+Nitro-S) demonstrated the greatest PD reduction, followed by local statins (Statins-L) in the short term (≤3 months). Statins-L also provided the highest CAL gain. In the medium term (4-6 months), Statins-L remained the most effective, followed by bisphosphonates. For long-term (>6 months) follow-up, where fewer treatment approaches were available, Nitro-S achieved the most significant PD reduction and CAL gain, followed by Mac/Linc-S. Adverse effects were mild and self-limiting. Despite promising findings, inconsistencies in CAL outcomes and potential publication bias highlight the need for further research to confirm long-term safety and efficacy.enAdjunctive periodontal treatmentAggressive periodontitisMeta-analysisNon-surgical periodontal therapyStage III/IV Grade Cjournal article10.1016/j.jdsr.2025.07.00140697931