Department of Clinical Medicine, Nephrology, and Health Sciences, University Hospital, Parma, Italy.
Lancet. 2011 Jul 23;378(9788):338-46. doi: 10.1016/S0140-6736(11)60934-3. Epub 2011 Jul 4.
Glucocorticoids are the mainstay of treatment of idiopathic retroperitoneal fibrosis, but they often have substantial toxic effects. Several reports have suggested tamoxifen as an alternative to glucocorticoids. We compared the efficacy of prednisone with that of tamoxifen in maintainance of remission in patients with idiopathic retroperitoneal fibrosis.
In this open-label, randomised controlled trial, we enrolled patients aged 18-85 years with newly diagnosed idiopathic retroperitoneal fibrosis at the Parma Hospital, Parma, Italy, between Oct 1, 2000, and June 30, 2006. After induction therapy with 1 mg/kg daily of prednisone for 1 month, the patients who achieved remission were randomly assigned to receive tapering prednisone (initial dose 0·5 mg/kg daily) for 8 months or tamoxifen (fixed dose 0·5 mg/kg daily) for 8 months. The sequence of randomisation (1:1), blocked in groups of two and four (with block size randomly selected), was generated by the trial statistician with a computer programme. After the end of treatment, the patients were followed up for an additional 18 months. Neither patients nor those giving interventions or analysing the data were masked to group assignment. The two radiologists who assessed CT and MRI scans were masked. The primary endpoint was the relapse rate by the end of treatment (month 8), which was analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00440349.
After induction therapy, 36 of the 40 enrolled patients achieved remission and were randomly assigned to treatment (18 per group). One patient (6%) in the prednisone group and seven patients (39%) in the tamoxifen group relapsed by the end of treatment (difference -33% [95% CI -58 to -8, p=0·0408]. The difference in relapse rate between the groups was sustained after the additional 18-month follow-up: the 26-month estimated cumulative relapse probability was 17% with prednisone and 50% with tamoxifen (difference -33% [-62 to -3, p=0·0372]). Cushingoid changes and grade 2 hypercholesterolaemia were more common in the prednisone group than in the tamoxifen group (p=0·0116 and p=0·0408, respectively).
Prednisone is more effective in prevention of relapses than is tamoxifen in patients with idiopathic retroperitoneal fibrosis. Therefore, prednisone should be considered as first-line treatment for patients with newly diagnosed idiopathic retroperitoneal fibrosis.
Parma University Hospital.
糖皮质激素是特发性腹膜后纤维化治疗的基础，但它们通常具有较大的毒性作用。一些报道提示他莫昔芬可作为糖皮质激素的替代药物。我们比较了泼尼松和他莫昔芬在维持特发性腹膜后纤维化患者缓解方面的疗效。
在这项开放标签、随机对照试验中，我们招募了意大利帕尔马医院在 2000 年 10 月 1 日至 2006 年 6 月 30 日期间新诊断为特发性腹膜后纤维化的年龄在 18-85 岁之间的患者。在接受 1 毫克/千克/天的泼尼松诱导治疗 1 个月后，达到缓解的患者被随机分配接受泼尼松逐渐减量（初始剂量为 0.5 毫克/千克/天）治疗 8 个月或他莫昔芬（固定剂量 0.5 毫克/千克/天）治疗 8 个月。随机化序列（1:1），按 2 人和 4 人的分组进行分组（块大小随机选择），由试验统计员使用计算机程序生成。治疗结束后，患者再进行额外的 18 个月随访。患者、进行干预的人员和分析数据的人员均不了解分组情况。评估 CT 和 MRI 扫描的两名放射科医生对分组情况进行了盲法评估。主要终点是治疗结束时（第 8 个月）的复发率，这通过意向治疗进行分析。该试验在 ClinicalTrials.gov 注册，编号为 NCT00440349。
在诱导治疗后，40 名入组患者中有 36 名达到缓解并被随机分配到治疗组（每组 18 名）。泼尼松组中有 1 名患者（6%）和他莫昔芬组中有 7 名患者（39%）在治疗结束时复发（差异-33%[95%CI-58 至-8，p=0.0408]）。在额外的 18 个月随访后，两组之间的复发率差异持续存在：泼尼松组 26 个月的累积复发概率为 17%，而他莫昔芬组为 50%（差异-33%[-62 至-3，p=0.0372]）。泼尼松组中库欣样改变和 2 级高胆固醇血症的发生率高于他莫昔芬组（p=0.0116 和 p=0.0408）。
泼尼松在预防特发性腹膜后纤维化患者复发方面比他莫昔芬更有效。因此，泼尼松应被视为新诊断的特发性腹膜后纤维化患者的一线治疗药物。
帕尔马大学医院。
