Prospective study of TNFα blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis
Prospective study of TNFα blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis
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DOI：
10.1097/01.asn.0000114554.67106.28
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发表时间：
2004-03-01
影响因子：
13.6
通讯作者：
Jayne, D
中科院分区：
文献类型：
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作者：
Booth, A;Harper, L;Jayne, D
肿瘤坏死因子α在抗中性粒细胞胞浆抗体相关性系统性小血管炎的发病机制中起重要作用。TNFa阻断是治疗这些疾病的一种潜在疗法。方法：采用开放、多中心、前瞻性临床试验，分两组进行。研究一检查急性疾病，无论是首次出现还是复发(伯明翰血管炎活动评分[BVAS]大于或等于10；n=16)；研究II检查持续性疾病(BVAS>4；n=16)。患者在0、2、6和10wk时给予英夫利昔单抗(5 mg/kg)。研究I的同期治疗包括强的松龙和环磷酰胺。研究II患者继续他们现有的治疗方案，根据临床情况逐渐减少强的松龙。结果：平均年龄52.4岁，女性占53%，随访16.8个月。28名患者(88%)获得缓解(每个研究组14名)。BVAS从入院时的12.3(可信区间[CI]=10.5降至14.0)降至第14周(P<；0.001)的0.3%(CI=0.2至0.9)。C反应蛋白(mg/L)在第14周时由入院时的29.4(CI=16.8~42.0)降至7.0(CI=3.3~10.9)(P=0.001)。研究II的平均强的松龙剂量(mg/d)从入院时的23·8(CI=15·0~32·5)下降到wk 14的8·8(CI=5·9~11·7)(P=0.002)。有两人死亡，七人严重感染。平均27wk后，5名患者(3名患者II)复发。结论：用英夫利昔单抗阻断肿瘤坏死因子α能有效地缓解88%的抗体相关性系统性小血管炎患者，并允许减少类固醇的剂量。21%的患者出现了严重感染，尽管英夫利昔单抗持续存在，但20%的初始应答者经历了疾病爆发。英夫利昔单抗是一种很有前途的治疗血管炎的新疗法，无论是作为初始治疗的组成部分还是在治疗难治性疾病方面都是如此。这些结果需要在更大规模的随机试验中得到证实。
Tumor necrosis factor alpha (TNFalpha) plays an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. TNFa blockade is a potential therapy for these disorders. Methods: An open-label, multi-center, prospective clinical trial in two subgroups was performed. Study I examined acute disease, either first presentation or relapse (Birmingham Vasculitis Activity Score [BVAS] greater than or equal to 10; n = 16); study II examined persistent disease (BVAS greater than or equal to 4; n = 16). Patients received infliximab (5 mg/kg) at 0, 2, 6, and 10 wk. Concomitant therapy in study I included prednisolone and cyclophosphamide. Study II patients continued their existing treatment regimens, with prednisolone tapered according to clinical status. Results: Mean age was 52.4 yr, 53% of the patients were female, and follow-up wads 16.8 mo. Twenty-eight patients (88%) achieved remission (14 per study group). BVAS decreased from 12.3 (confidence interval [CI] = 10.5 to 14.0) at entry to 0.3 (CI = 0.2 to 0.9) at wk 14 (P < 0.001). C-reactive protein (mg/L) decreased from 29.4 (CI = 16.8 to 42.0) Lit entry to 7.0 (CI = 3.3 to 10.9) by wk 14 (P = 0.001). Mean prednisolone dose (mg/d) in study II decreased from 23.8 (CI = 15.0 to 32.5) at entry to 8.8 (CI = 5.9 to 11.7) at wk 14 (P = 0.002). There were two deaths and seven serious infections. Relapse occurred in five patients (three ill study II) after a mean of 27 wk. Conclusion: TNFalpha blockade with infliximab was effective at inducing remission in 88% of patients with antibody-associated systemic vasculitis and permitted reduction in steroid doses. Severe infections were seen in 21% of patients, and despite continued infliximab, 20% of initial responders experienced disease flares. Infliximab is a promising new therapy for vasculitis both as a component of initial therapy and in the management of refractory disease. These results need confirmation in larger randomized trials.