非手術性牙周治療中宿主調節劑的輔助應用：系統性回顧與網絡統合分析

Abstract

背景 本系統性回顧與網絡統合分析（NMA）旨在評估現有口服系統性宿主調節劑作為非手術性牙周治療（NSPT）輔助用藥，在非合併全身疾病之牙周炎患者中對臨床牙周指標（探測深度（PPD）及臨床附連水平（CAL））改善之療效。 材料與方法 我們於 2025 年 2 月前，系統性搜尋電子資料庫並手動篩查相關文獻，以納入符合條件之隨機對照試驗，研究對象為年滿 18 歲、無全身性疾病的牙周炎成人患者，接受全口非手術性牙周治療（NSPT），單獨進行或合併口服系統性宿主調節劑。研究設計依 PICO 架構制定：受試者為接受 NSPT 之牙周炎成人患者；介入措施為 NSPT 合併系統性宿主調節劑；比較對象為單純 SRP 或 SRP 合併安慰劑；主要結果為全口平均探測深度（PPD）減少，次要結果為全口平均臨床附連水平（CAL）增加。我們計算各比較組間的平均差值及 95%信賴區間，並進行隨機效應網絡統合分析，以整合直接與間接證據，並產出各輔助療法的綜合療效排名。 結果 本分析共納入 49 篇隨機對照試驗，涵蓋 1125 位系統性健康的牙周病成人患者，並以對比式隨機效應網絡統合分析加以整合。與單純 SRP 或 SRP 加安慰劑相比，輔助使用系統性宿主調節劑，在短期（≤ 3 個月）追蹤中，PPD 減少以褪黑激素（melatonin）最顯著，達 0.69 mm，其 SUCRA 值為 86.2%；中期（4-6 個月）亦以褪黑激素效果最佳，達 1.08 mm，SUCRA 值為 96.1%；長期（≥ 7 個月）則由益生菌（probiotics）表現最優，達 0.82 mm，SUCRA 值為 90.0%。在 CAL 增加方面，短期以褪黑激素最為顯著，達 0.98 mm，SUCRA 值為 94.5%；中期仍以褪黑激素表現最佳，達 1.22 mm，SUCRA 值為 92.5%；長期則由非類固醇抗發炎藥（NSAID）效果最佳，達 0.79 mm，SUCRA 值為 69.2%。所有納入試驗中皆未報告嚴重不良反應，且71%的研究被評為低偏倚風險，支持本研究結果的可信度。 結論 系統性宿主調節劑作為非手術治療的輔助方式，可能僅具有限但潛在有益的效果，其中褪黑激素在短期與中期的 PPD 與 CAL 改善最為顯著，益生菌在 PPD 的長期療效中表現最佳，而 CAL 的長期改善則以 NSAID 效果最優。

Background: The aim of this systematic review and NMA was to evaluate the efficacy of the currently available host-modulating agents as adjuncts to NSPT in non-medically compromised periodontitis patients, focusing on improved clinical periodontal outcomes, including changes in PPD and CAL. Materials and Methods: A systematic search of electronic databases and manual reference screening was performed through February 2025 to identify randomized controlled trials enrolling medically uncompromised adults (≥18 years) with periodontitis who underwent full-mouth NSPT alone or in combination with oral systemic host-modulating agents. Following a PICO framework—Population: adults with periodontitis receiving NSPT; Intervention: adjunctive systemic host modulators plus NSPT; Comparison: SRP alone or SRP + placebo; Outcomes: full mouth mean PPD reduction (primary) and full mouth mean CAL gain (secondary)—we calculated mean differences with 95 % CI for each comparison. A random-effects network meta-analysis was then conducted to integrate direct and indirect evidence, generating a comprehensive efficacy ranking of the adjunctive therapies. Results: This analysis included 49 randomized controlled trials involving 1,125 systemically healthy adults with periodontitis and was synthesized using a contrast-based random-effects network meta-analysis. Compared with SRP alone or SRP with placebo, adjunctive use of systemic host modulators showed the most pronounced PPD reduction in the short term (≤ 3 months) with melatonin (0.69 mm, SUCRA = 86.2%), followed by melatonin again in the medium term (4–6 months) (1.08 mm, SUCRA = 96.1%), and probiotics in the long term (≥ 7 months) (0.82 mm, SUCRA = 90.0%). For CAL gain, melatonin also demonstrated the greatest effect in the short term (0.98 mm, SUCRA = 94.5%) and remained the most effective in the medium term (1.22 mm, SUCRA = 92.5%), while NSAIDs ranked highest in the long term (0.79 mm, SUCRA = 69.2%). No serious adverse events were reported in any included trials, and 71% of studies were rated as having a low risk of bias, supporting the credibility of the findings. Conclusions: Adjunctive systemic host modulators may provide limited yet potentially favorable effects following non-surgical therapy, with melatonin most effective for short- and medium-term PPD and CAL improvement, probiotics showing long-term benefit for PPD, and NSAIDs for long-term CAL.