Schotte H, Schorat M A, Willeke P, Domschke W, Gaubitz M
Medizinische Klinik und Poliklinik B, Universitätsklinikum Münster, Albert-Schweitzer-Str. 33, 48129, Münster, Germany.
Z Rheumatol. 2005 May;64(4):265-73. doi: 10.1007/s00393-005-0675-y.
The tumor necrosis factor blocking agent etanercept is effective in the treatment of chronic inflammatory diseases. Previously published studies provided no evidence for an elevated frequency of severe adverse events under therapy. The present work documents efficacy and safety of long-term treatment with etanercept up to four years in 29 patients with rheumatoid arthritis in single German study center. Follow-up examinations were conducted at monthly intervals. The response was assessed in an intention-to-treat analysis (last observation carried forward) according to the ACR and EULAR criteria. The evaluation is based on 95 patient years, the median observation period was 50 (4-52) months. After four years, 21 patients were still in the study. Reasons for study dropouts were inefficacy (n=3), severe adverse events (n=1), long distance to study center (n=2), scheduled surgery (n=1), and desire for pregnancy (n=1). Morning stiffness, the number of painful and swollen joints, C-reactive protein, erythrocyte sedimentation rate, and DAS28 significantly decreased within 6 months. At their most recent visit, 26 patients (90%) had achieved the ACR20, 17 patients (59%) the ACR50, and 6 patients (21%) the ACR70 criteria. Subject to the EULAR criteria, 14 patients (48%) responded well and another 12 patients (41%) moderately well. Severe adverse events occurred in the form of a sigma perforation with subsequent sepsis (week 17), suture insufficiency (twice) following rupture of an Achilles tendon (weeks 3 and 9), pneumonia (week 121), and breast cancer (week 197). In our patients, long-term treatment with etanercept continued to be effective and safe up to four years. Severe adverse events were rare and not more frequent than expected. For the detection of uncommon or late occurring severe adverse events under the treatment with biologic agents, documentation in central registers should be encouraged.
肿瘤坏死因子阻断剂依那西普在慢性炎症性疾病的治疗中有效。先前发表的研究未提供治疗期间严重不良事件发生率升高的证据。本研究记录了德国单个研究中心29例类风湿关节炎患者接受依那西普长达四年的长期治疗的疗效和安全性。每月进行随访检查。根据美国风湿病学会（ACR）和欧洲抗风湿病联盟（EULAR）标准，在意向性治疗分析（末次观察结转）中评估反应。评估基于95患者年，中位观察期为50（4 - 52）个月。四年后，21例患者仍在研究中。退出研究的原因包括无效（n = 3）、严重不良事件（n = 1）、距离研究中心路途遥远（n = 2）、计划手术（n = 1）和怀孕意愿（n = 1）。晨僵、疼痛和肿胀关节数量、C反应蛋白、红细胞沉降率和疾病活动度评分（DAS28）在6个月内显著下降。在最近一次就诊时，26例患者（90%）达到ACR20标准，17例患者（59%）达到ACR50标准, 6例患者（21%）达到ACR70标准。根据EULAR标准，14例患者（48%）反应良好，另外12例患者（41%）反应中等。严重不良事件包括乙状结肠穿孔继发败血症（第17周）、跟腱断裂后缝线不充分（两次，分别在第3周和第9周）、肺炎（第121周）和乳腺癌（第197周）。在我们的患者中，依那西普长达四年的长期治疗持续有效且安全。严重不良事件罕见，且不比预期更频繁。为了检测生物制剂治疗下不常见或迟发性严重不良事件，应鼓励在中央登记处进行记录。
