Supplementary file 1_Evaluating calcineurin inhibitors as alternatives to steroids in treating Oral Lichen Planus: a systematic review and meta-analysis.docx

IntroductionOral Lichen Planus is a chronic inflammatory disease and a potentially malignant disorder of the oral mucosa. We aimed to investigate the possibility of replacing the gold-standard steroids (ST) due to their propensity for drug tolerance and numerous associated side effects. Recently, calcineurin inhibitors (CNI) have emerged as a promising alternative to ST. The main objective of the recent study was to compare the therapeutic effects of CNI and ST on OLP through pain severity, lesion morphology, and adverse effects.
Materials and methodsA systematic search was conducted in 4 databases (Pubmed, Embase, Central, and Web of Science) on November 26th, 2023. Randomized controlled trials (RCTs) were selected for the analysis, which compared topically used CNIs, STs, or placebo. The outcomes were pain severity, oral mucosa morphology, and safety (adverse effects, especially transient burning). Odds ratios (ORs) and mean differences (MDs) with the random-effects model were calculated in the quantitative synthesis and interpreted with 95% confidence intervals (CIs).
ResultsA total of eleven RCTs were selected for quantitative analysis. Topically applied ST tended to decrease pain after four weeks of treatment (MD: −0.06, 95%CI: −0.55; 0.44) and promoted healing better (MD: −0.08, 95%CI: −0.74; 0.57) than measured in CNI therapy. Transient burning occurred more often in the CNI group (OR: 2.45, 95%CI: 0.55; 10.85).
DiscussionTopical STs and topically used CNIs have a similar effect. However, data show a higher rate of side effects with CNI, particularly transient burning during the first two days of treatment.
Clinical relevanceTopical STs and topically used CNIs have a similar effect. However, data show a higher rate of side effects with CNI, particularly transient burning during the first two days of treatment. Topically applied STs may remain the gold standard for symptomatic OLP. The evidence is currently insufficient to support replacing ST with CNI in OLP treatment in routine clinical practice.
Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023486435, PROSPERO CRD42023486435.

引言
口腔扁平苔藓（Oral Lichen Planus，OLP）是一种慢性炎症性疾病，同时属于口腔黏膜潜在恶性病变范畴。本研究旨在探究由于糖皮质激素（steroids，ST）存在药物耐受倾向及诸多相关不良反应，是否可将其作为OLP一线治疗方案替代的可行性。近年来，钙调磷酸酶抑制剂（calcineurin inhibitors，CNI）已成为ST颇具前景的替代方案。本系统综述的核心目标为通过疼痛严重程度、病损形态及不良反应三个维度，比较CNI与ST治疗OLP的疗效差异。

材料与方法
本研究于2023年11月26日在4个数据库（PubMed、Embase、Cochrane中央对照试验注册库（CENTRAL）及Web of Science）中开展系统检索。纳入分析的随机对照试验（randomized controlled trials，RCTs）需比较局部应用CNI、ST或安慰剂的疗效。本研究的结局指标包括疼痛严重程度、口腔黏膜病损形态及安全性（不良反应，尤其是一过性烧灼感）。定量合成阶段采用随机效应模型计算比值比（odds ratios，ORs）与均数差（mean differences，MDs），并以95%置信区间（confidence intervals，CIs）进行结果解读。

结果
最终共纳入11项RCTs开展定量分析。治疗4周后，局部应用ST的疼痛缓解效果优于CNI治疗（均数差：-0.06，95%置信区间：-0.55~0.44），且病损愈合效果更优（均数差：-0.08，95%置信区间：-0.74~0.57）。CNI组一过性烧灼感的发生率更高（比值比：2.45，95%置信区间：0.55~10.85）。

讨论
局部应用ST与CNI的疗效相近，但现有数据显示CNI的不良反应发生率更高，尤以治疗前两日出现的一过性烧灼感为著。

临床意义
局部应用ST与CNI的疗效相近，但现有数据显示CNI的不良反应发生率更高，尤以治疗前两日出现的一过性烧灼感为著。局部应用ST或仍是症状性OLP的金标准治疗方案，当前证据尚不支持在临床常规OLP治疗中以CNI替代ST。

系统综述注册信息
https://www.crd.york.ac.uk/PROSPERO/view/CRD42023486435，注册编号为PROSPERO CRD42023486435。