丁泓帆 徐潇 李仕一 王一晨 吴倩 白瑞琪 周桂文 付强 刘悦 陈敏亮

本文来源：《中华整形外科杂志》2023年12月 第39卷 第12期

DOI:10. 3760 / cma.j.cn114453-20230323-00063

作者单位：解放军总医院第四医学中心烧伤整形医学部， 北京100048

通信作者：陈敏亮，Email：chenml@sohu.com

【摘要】 

目的 利用网状meta分析的方法比较不同药物注射治疗瘢痕疙瘩的有效性和安全性。

方法在PubMed、Embase、Web of Science中以"triamcinolone acetonide，5-fluorouracil，verapamil，botulinum toxin，platelet rich plasma，drug injection，scar，keloid"为检索词，在中国知网、万方数据库中以"曲安奈德，5-氟尿嘧啶，维拉帕米，肉毒毒素，富血小板血浆，瘢痕，药物注射"为检索词，检索自2010年1月至2023年2月公开发表的比较单一或者联合药物注射治疗瘢痕疙瘩的随机对照试验研究。结局指标为治疗有效率、复发率和不良反应情况。利用NoteExpress、RevMan 5.4和Stata 16.0统计软件对符合纳入、排除标准的研究进行网状meta分析。

结果 共纳入21篇文献，1 679例患者，包括9项治疗措施：曲安奈德(TAC)，5-氟尿嘧啶(5-FU)，A型肉毒毒素(BTA)，富血小板血浆(PRP)，维拉帕米(Verapamil)，BTA＋5-FU，TAC＋5-FU，TAC＋BTA，TAC＋PRP。网络图显示，9项治疗措施可形成36个不同的两两比较，其中13个有直接证据比较。漏斗图显示各效应量点基本对称，Beggs检验及Eggers检验 P值均大于0.05，说明存在发表偏倚的可能性较小。9项治疗措施直接形成5个闭环，各闭环一致性较好。网状meta分析结果显示：9项治疗措施两两之间比较，BTA＋5-FU的治疗有效率高于单独TAC或5-FU或PRP，TAC＋5-FU的治疗有效率高于单独TAC或5-FU或PRP，TAC＋BTA的治疗有效率高于单独TAC或5-FU或BTA或PRP，Verapamil的治疗有效率高于5-FU，BTA的治疗有效率高于5-FU，以上比较差异均有统计学意义( P<0.05)。累积排序概率曲线下面积(SUCRA)图显示各治疗措施治疗有效率排序及SUCRA值为：BTA＋5-FU(85.6%)>TAC＋5-FU(84.8%)>BTA＋TAC(76.7%)>Verapamil (48.9%)>BTA(45.0%)>TAC＋PRP(43.8%)>PRP(32.1%)> TAC(24.7%)>5-FU(8.3%)。在复发率方面，5-FU复发率高于单独BTA或TAC＋5-FU，TAC复发率高于TAC＋5-FU，以上比较差异均有统计学意义( P<0.05)。SUCRA图显示各治疗措施复发率排序及SUCRA值为：5-FU(80.4%)>TAC(73.5%)>Verapamil(65.7%)>TAC＋BTA(52.5%)>PRP(34.8%)>BTA＋5-FU(33.7%)>TAC＋5-FU(30.2%)>BTA(29.3%)。定性分析不良反应提示联合药物注射的全身和局部不良反应发生比例均明显低于单一药物注射。

结论 在瘢痕疙瘩药物注射治疗中，药物联合注射治疗较单一注射治疗往往能取得更优的疗效、更低的复发率及更少的不良反应，其中，BAT、5-FU及TAC之间的联合治疗可能会取得最佳效力。

Comparisons of the efficacy of drug injections for the treatment of keloid: a network meta-analysis

Ding  Hongfan, Xu  Xiao, Li  Shiyi, Wang  Yichen, Wu  Qian, Bai  Ruiqi, Zhou  Guiwen, Fu  Qiang, Liu  Yue, Chen  Minliang

Senior Department of Burns and Plastic Surgery, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China

Corresponding author:  Chen Minliang, Email: chenml@sohu.com

  【Abstract】

Objective To conduct a network meta-analysis comparing the efficacy and safety of various drug injections for treating keloids.

Methods The search terms of "triamcinolone acetonide, 5-fluorouracil, verapamil, botulinum toxin, platelet rich plasma, keloid, scar, drug injection" were retrieved in PubMed, Embase, Web of Science, CNKI and Wanfang database to obtain the publicly published randomized controlled trials comparing single or combined drug injection for treating keloid from January 2010 to February 2023. The outcome index was the effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion. NoteExpress, RevMan 5.4, and Stata 16.0 statistical software were utilized to perform a network meta-analysis of eligible studies that met the inclusion and exclusion criteria.

Results A total of 1 679 patients were enrolled in 21 studies that evaluated nine treatment modalities: triamcinolone (TAC), 5-fluorouracil (5-FU), botulinum toxin type A (BTA), platelet-rich plasma (PRP), Verapamil, BTA+ 5-FU, TAC+ 5-FU, TAC+ BTA, and TAC+ PRP. The network diagram revealed that there were 36 pairwise comparisons among the 9 treatment measures, with direct comparisons in 13 of them. The funnel plot demonstrated a symmetrical distribution of effect size points, and both Beggs test and Eggers test yielded P values greater than 0.05, indicating a low likelihood of publication bias. Nine treatment measures formed five closed loops with good consistency. The result of the network meta-analysis indicated that BTA+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ BTA was more effective than TAC, 5-FU, BTA, or PRP alone; Verapamil was more effective than 5-FU and BTA was more effective than 5-FU. All result were found to be statistically significant ( P<0.05). A surface under the cumulative ranking area (SUCRA) map was generated, displaying the efficacy ranking and corresponding SUCRA values for each treatment: BTA+ 5-FU (85.6%)>TAC+ 5-FU (84.8%)>BTA+ TAC (76.7%)>Verapamil (48.9%)>BTA (45.0%)>TAC+ PRP (43.8%)>PRP (32.1%)>TAC (24.7%)>5-FU(8.3%). In terms of recurrence rate, the incidence of recurrence was higher with 5-FU compared to BTA or TAC+ 5-FU, and the incidence of recurrence was higher with TAC compared to TAC+ 5-FU; these differences were statistically significant ( P<0.05). A SUCRA map was generated with the ranking and SUCRA value for each treatment as follows: 5-FU (80.4%)>TAC (73.5%)>Verapamil (65.7%)>TAC+ BTA (52.5%)>PRP (34.8%)>BTA+ 5-FU (33.7%)>TAC+ 5-FU (30.2%)>BTA (29.3%). The qualitative analysis revealed a significantly lower incidence of systemic and local adverse reactions following combined drug injection compared to single drug injection.

Conclusion In the treatment of keloids using drug injection, combination therapy utilizing multiple drugs has demonstrated superior efficacy, lower recurrence rates, and fewer adverse reactions in comparison to single-drug therapy. Notably, the utilization of BAT, 5-FU, and TAC in combination may yield the most favorable outcomes.

Disclosure of Conflicts of Interest: The authors have no financial interest to declare in relation to the content of this article.