McMaster University, Hamilton, Ontario, Canada.
Arthritis Care Res (Hoboken). 2013 Sep;65(9):1460-71. doi: 10.1002/acr.22018.
To assess the efficacy of therapies in healing and preventing digital ulcers (DUs) in systemic sclerosis (SSc; scleroderma).
Medline and EMBASE databases, and American College of Rheumatology and European League Against Rheumatism abstracts, were searched. Randomized controlled trials (RCTs) with outcomes investigating healing or prevention of DUs in SSc and comparing a pharmacologic therapy with placebo or an active agent were included. The pooled risk ratios (RRs) using the fixed-effects model were calculated and heterogeneity was tested using the I(2) statistic.
Sixty studies were found; 19 were not randomized, and 10 did not give DU quantitative data or no comparison of a different drug, leaving 31 RCTs with a total of 1,989 patients. Quality was 3 of 5 or less for 11 trials. DUs were not the primary outcome in many RCTs. Phosphodiesterase type 5 (PDE-5) inhibitors were significant for DU healing (RR 3.28 [95% confidence interval (95% CI) 1.32, 8.13], P = 0.01). Two large bosentan trials were significant for mean number of new DUs (standardized mean difference [SMD] -0.34 [95% CI -0.57, -0.11], P = 0.004). Oral prostacyclins were not statistically different from placebo, but intravenous (IV) iloprost prevented new DUs (SMD 0.77 [95% CI -1.46, -0.08], P = 0.03). Single trials for atorvastatin and vitamin E were positive in the prevention and healing of DU, respectively. There were many negative trials: antiplatelet therapy, oral N-acetylcysteine, heparin, dimethyl sulfoxide, ketanserin, prazosin, prostaglandin E1, cyclofenil, quinapril, and topical nitroglycerin formulation.
Small sample sizes, few comparative trials, and heterogeneity limits the conclusions. The results suggest a role for PDE-5 inhibitors in the healing of DUs; bosentan and IV iloprost may prevent new DUs.
评估治疗系统性硬化症（SSc；硬皮病）患者手指溃疡（DU）愈合和预防 DU 的疗效。
检索 Medline 和 EMBASE 数据库以及美国风湿病学会和欧洲抗风湿病联盟摘要，纳入比较药物治疗与安慰剂或活性药物治疗 SSc 患者 DU 愈合或预防的随机对照试验（RCT）。使用固定效应模型计算汇总风险比（RR），并用 I(2) 统计量检验异质性。
共发现 60 项研究，其中 19 项非随机，10 项未提供 DU 定量数据或未比较不同药物，仅 31 项 RCT 共 1989 例患者符合纳入标准。11 项试验质量评分为 3 分或以下。许多 RCT 中 DU 并非主要结局。磷酸二酯酶 5（PDE-5）抑制剂对 DU 愈合有显著效果（RR 3.28 [95%可信区间 95%CI 1.32，8.13]，P = 0.01）。2 项大型波生坦试验对新发 DU 数量有显著影响（标准化均数差 SMD -0.34 [95%CI -0.57，-0.11]，P = 0.004）。口服前列环素与安慰剂相比无统计学差异，但静脉注射（IV）依前列醇可预防新发 DU（SMD 0.77 [95%CI -1.46，-0.08]，P = 0.03）。阿托伐他汀和维生素 E 的单药治疗试验在 DU 预防和愈合方面分别为阳性。也有许多阴性试验：抗血小板治疗、口服 N-乙酰半胱氨酸、肝素、二甲基亚砜、酮色林、哌唑嗪、前列腺素 E1、环芬尼、喹那普利和硝酸甘油制剂。
样本量小、比较试验少和异质性限制了结论。结果提示 PDE-5 抑制剂在 DU 愈合中可能有作用；波生坦和 IV 依前列醇可能预防新发 DU。
