甲氧苄啶-磺胺甲恶唑（复方新诺明）预防韦格纳肉芽肿复发。荷兰复方新诺明韦格纳研究组。

Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co-Trimoxazole Wegener Study Group.

作者信息

Stegeman C A, Tervaert J W, de Jong P E, Kallenberg C G

机构信息

Department of Medicine, University Hospital, Groningen, The Netherlands.

出版信息

N Engl J Med. 1996 Jul 4;335(1):16-20. doi: 10.1056/NEJM199607043350103.

DOI:10.1056/NEJM199607043350103

PMID:8637536

Abstract

BACKGROUND

Respiratory tract infections may trigger relapses in patients with Wegener's granulomatosis in remission. Uncontrolled data have suggested that treatment with trimethoprim-sulfamethoxazole (co-trimoxazole) may be beneficial.

METHODS

We conducted a prospective, randomized, placebo-controlled study of the efficacy of co-trimoxazole (800 mg of sulfamethoxazole and 160 mg of trimethoprim) given twice daily for 24 months in preventing relapses in patients with Wegener's granulomatosis in remission during or after treatment with cyclophosphamide and prednisolone. Relapses and infections were assessed with predefined criteria based on clinical, laboratory, and histopathological findings. Patients were evaluated at least once every three months for signs of disease activity, compliance with the treatment regimen, side effects of the therapy, and evidence of infections. Titers of serum antineutrophil cytoplasmic antibodies were measured serially.

RESULTS

Forty-one patients were assigned to receive co-trimoxazole, and 40 to receive placebo. In 8 of the 41 patients in the co-trimoxazole group (20 percent), the drug had to be stopped because of side effects. According to life-table analysis, 82 percent of the patients remained in remission at 24 months, as compared with 60 percent of the patients in the placebo group (relative risk of relapse, 0.40; 95 percent confidence interval, 0.17 to 0.98). There were fewer respiratory tract infections (P = 0.005) and non-respiratory tract infections (P = 0.05) in the co-trimoxazole group than in the placebo group. There were no significant differences in antineutrophil cytoplasmic antibody titers at any time. Proportional-hazards regression analysis identified treatment with co-trimoxazole as an independent factor associated with prolonged disease-free survival and a positive antineutrophil cytoplasmic antibody test at the start of treatment as a risk factor for relapse.

CONCLUSIONS

Treatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener's granulomatosis in remission.

摘要

背景

呼吸道感染可能会引发处于缓解期的韦格纳肉芽肿病患者病情复发。未经对照的数据提示，甲氧苄啶-磺胺甲恶唑（复方新诺明）治疗可能有益。

方法

我们开展了一项前瞻性、随机、安慰剂对照研究，以评估复方新诺明（800毫克磺胺甲恶唑和160毫克甲氧苄啶）每日两次给药共24个月，对接受环磷酰胺和泼尼松龙治疗期间或之后处于缓解期的韦格纳肉芽肿病患者预防复发的疗效。根据基于临床、实验室和组织病理学检查结果预先确定的标准评估复发和感染情况。每三个月至少对患者评估一次疾病活动迹象、治疗方案依从性、治疗副作用及感染证据。连续检测血清抗中性粒细胞胞浆抗体滴度。

结果

41例患者被分配接受复方新诺明治疗，40例接受安慰剂治疗。复方新诺明组41例患者中有8例（20%）因副作用而停药。根据生存表分析，24个月时82%的患者仍处于缓解期，而安慰剂组为60%（复发相对风险为0.40；95%置信区间为0.17至0.98）。复方新诺明组的呼吸道感染（P = 0.005）和非呼吸道感染（P = 0.05）少于安慰剂组。在任何时间点，抗中性粒细胞胞浆抗体滴度均无显著差异。比例风险回归分析确定，复方新诺明治疗是与无病生存期延长相关的独立因素，治疗开始时抗中性粒细胞胞浆抗体检测呈阳性是复发的危险因素。