Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis - A randomized trial
Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis - A randomized trial
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DOI：
10.7326/0003-4819-146-9-200705010-00004
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发表时间：
2007-05-01
影响因子：
39.2
通讯作者：
Rahman, Mahboob U.
中科院分区：
文献类型：
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作者：
Hoffman, Gary S.;Cid, Maria C.;Rahman, Mahboob U.
背景：肿瘤坏死因子-α存在于巨细胞动脉炎的动脉中。目的：评价抗肿瘤坏死因子-α药物英夫利昔单抗治疗巨细胞动脉炎的疗效。设计：随机对照试验。地点：美国、英国、比利时、意大利和西班牙的22个地点。患者：44名新诊断的巨细胞大动脉炎患者在糖皮质激素诱导的缓解中。干预：参与者按2：1的比例随机分配接受英夫利昔单抗(5 mg/kg体重)或安慰剂。16名患者被分配给糖皮质激素加安慰剂，28名患者被分配给糖皮质激素加英夫利昔布。测量：终点测量一直持续到第22周，当时的中期分析导致计划的54周试验提前停止。主要终点是指在22周内没有复发和不良事件的患者数量。次要终点是首次复发时间、生物标志物、累积糖皮质激素剂量，以及在糖皮质激素剂量逐渐减少到10 mg/d时保持无复发的患者数量。结果：与安慰剂相比，英夫利昔单抗治疗在第22周没有增加无复发患者的比例(分别为43%和50%；差异，-7个百分点[95%CI，-38到23个百分点；P=0.65]，也没有增加糖皮质激素剂量减少到10 mg/d无复发患者的比例(分别为61%和75%；差异-14个百分点[CI，-42至14个百分点]；P=0.31)。英夫利昔单抗的感染率为71%，安慰剂为56%(差异15个百分点[CI，-14至45个百分点])。限制：样本太小，不能排除英夫利昔单抗的轻微影响，而且只包括新诊断的患者。只评估了一剂英夫利昔单抗，研究提前结束。结论：这项试验规模太小，不能得出明确的结论，但它提供了证据，证明在糖皮质激素诱导的新诊断巨细胞动脉炎缓解的患者中，使用英夫利昔单抗作为维持治疗是没有好处的，可能是有害的。如果英夫利昔单抗有好处，它不太可能是很好的。
Background: Tumor necrosis factor-alpha is present in arteries in giant cell arteritis.Objective: To evaluate the efficacy of infliximab, an anti-tumor necrosis factor-alpha agent, in giant cell arteritis.Design: Randomized, controlled trial.Setting: 22 sites in the United States, the United Kingdom, Belgium, Italy, and Spain.Patients: 44 patients with newly diagnosed giant cell arteritis that was in glucocorticosteroid-induced remission.Intervention: Participants were randomly assigned in a 2:1 ratio to receive infliximab (5 mg/kg of body weight) or placebo. Sixteen patients were assigned to glucocorticosteroid plus placebo, and 28 patients to glucocorticosteroid plus infliximab.Measurements: End points were measured through week 22, when an interim analysis resulted in early stopping of the planned 54-week trial. Primary end points were the number of patients who remained free of relapse through week 22 and adverse events. Secondary end points were time to first relapse, biomarkers, cumulative glucocorticosteroid dose, and the number of patients who remained relapse-free while the glucocorticosteroid dosage was tapered to 10 mg/d.Results: Infliximab therapy did not increase the proportion of patients without relapse at week 22 compared with placebo (43% vs. 50%, respectively; difference, -7 percentage points [95% CI, -38 to 23 percentage points; P = 0.65), nor did it increase the proportion of patients whose glucocorticosteroid dosages were tapered to 10 mg/d without relapse (61% vs. 75%, respectively; difference, -14 percentage points [CI, -42 to 14 percentage points]; P = 0.31). The incidence of infection was 71% with infliximab and 56% with placebo (difference, 15 percentage points [CI, -14 to 45 percentage points]).Limitations: The sample was too small to rule out modest effects of infliximab and included only patients with a new diagnosis. Only one dose of infliximab was evaluated, and the study was terminated early.Conclusions: This trial is too small to draw definitive conclusions, but it provides evidence that using infliximab as maintenance therapy in patients in glucocorticoid-induced remission of newly diagnosed giant cell arteritis is of no benefit and may be harmful. If infliximab has benefit, it is unlikely to be great.