Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement
Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement
复制标题
DOI：
10.1164/rccm.200603-402oc
复制
发表时间：
2006-10-01
影响因子：
24.7
通讯作者：
Barnathan, Elliot S.
中科院分区：
文献类型：
--
作者：
Baughman, Robert P.;Drent, Marjolein;Barnathan, Elliot S.
理由：有证据表明肿瘤坏死因子(TNF)- α在结节病的病理生理中起重要作用。目的：评价英夫利昔单抗治疗结节病的疗效。方法：对138例慢性肺结节病患者进行2期、多中心、随机、双盲、安慰剂对照研究。患者在第0、2、6、12、18和24周随机接受静脉输注英夫利昔单抗（3或5 mg/kg）或安慰剂，并随访至第52周。测量和主要结果：主要终点是从基线到第24周预测FVC的百分比变化。主要次要疗效参数包括圣乔治呼吸问卷、6分钟步行距离、Borg的CR10呼吸困难评分、面部皮肤受累的狼疮医师全球评估应答者比例。联合英夫利昔单抗组（3和5 mg/kg）的患者预测FVC的百分比从基线到第24周平均增加2.5%，而安慰剂治疗的患者没有变化（p = 0.038）。在第24周时，在任何主要次要终点上，治疗组之间没有观察到显著差异。事后探索性分析的结果表明，患有更严重疾病的患者往往从英夫利昔单抗治疗中获益更多。结论：英夫利昔单抗治疗导致第24周预测FVC %有统计学意义的改善。这一发现的临床重要性尚不清楚。这项2期临床研究的结果支持进一步评估抗tnf - α治疗严重、慢性、症状性结节病的疗效。
Rationale: Evidence suggests that tumor necrosis factor (TNF)-alpha plays an important role in the pathophysiology of sarcoidosis.Objectives: To assess the efficacy of infliximab in sarcoidosis.Methods: A phase 2, multicenter, randomized, double-blind, placebo-controlled study was conducted in 138 patients with chronic pulmonary sarcoidosis. Patients were randomized to receive intravenous infusions of infliximab (3 or 5 mg/kg) or placebo at Weeks 0, 2, 6, 12, 18, and 24 and were followed through Week 52.Measurements and Main Results: The primary endpoint was the change from baseline to Week 24 in percent of predicted FVC. Major secondary efficacy parameters included Saint George's Respiratory Questionnaire, 6-min walk distance, Borg's CR10 dyspnea score, and the proportion of Lupus Pernio Physician's Global Assessment responders for patients with facial skin involvement. Patients in the combined infliximab groups (3 and 5 mg/kg) had a mean increase of 2.5% from baseline to Week 24 in the percent of predicted FVC, compared with no change in placebo-treated patients (p = 0.038). No significant differences between the treatment groups were observed for any of the major secondary endpoints at Week 24. Results of post hoc exploratory analyses suggested that patients with more severe disease tended to benefit more from infliximab treatment.Conclusions: Infliximab therapy resulted in a statistically significant improvement in % predicted FVC at Week 24. The clinical importance of this finding is not clear. The results of this Phase 2 clinical study support further evaluation of anti-TNF-alpha therapy in severe, chronic, symptomatic sarcoidosis.