长期 TNF-α 阻断治疗伴发于风湿性疾病的淀粉样 A 淀粉样变患者。

Long-term TNF-alpha blockade in patients with amyloid A amyloidosis complicating rheumatic diseases.

机构信息

Servicio de Reumatología y Departamento de Medicina de la Facultad de Medicina, Hospital Regional Universitario Carlos Haya, Málaga, Spain.

出版信息

Am J Med. 2010 May;123(5):454-61. doi: 10.1016/j.amjmed.2009.11.010.

DOI:10.1016/j.amjmed.2009.11.010

PMID:20399323

Abstract

OBJECTIVE

To evaluate the effectiveness and safety of anti-tumor necrosis factor therapy in patients with amyloid A amyloidosis.

METHODS

Multicenter, controlled, dynamic prospective cohort study of 36 patients with amyloid A amyloidosis (94% kidney involvement) treated with anti-tumor necrosis factor agents (drug exposure of 102.97 patient-years). As an external control group, 35 propensity score-matched non-amyloid patients were chosen from the Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología registry. The end points were kidney response and progression, anti-tumor necrosis factor continuation rate, patient survival, and adverse events.

RESULTS

At the end of follow-up, a kidney response was observed in 12 of 22 patients (54.5%) and a kidney progression was observed in 6 of 36 patients (17%). The kidney amyloidosis remained stable in 16 of 36 patients (44%). The level of acute phase reactants diminished but did not reach the normal level. The continuation rates of anti-tumor necrosis factor drugs among patients with amyloid A amyloidosis after 1, 2, 3, and 4 or more years were 80%, 80%, 61%, and 52%, respectively, comparable to controls. The 5-year cumulative survival of amyloid A amyloidosis cases was 90.6%, and the 10-year survival was 78.5%. In a multivariate Cox regression analysis, the duration of amyloidosis and the level of proteinuria at the onset of anti-tumor necrosis factor treatment were independent predictors of treatment failure, whereas the level of proteinuria was the only factor that predicts mortality. Most adverse events were similar in both groups, although the number of infections was 3 times higher in amyloid A amyloidosis cases.

CONCLUSION

Anti-tumor necrosis factor drugs are effective in treating amyloid A amyloidosis, although they might increase the risk of infection.

摘要

目的

评估抗肿瘤坏死因子治疗在淀粉样 A 淀粉样变性患者中的疗效和安全性。

方法

对 36 例淀粉样 A 淀粉样变性（94%肾脏受累）患者进行多中心、对照、动态前瞻性队列研究，采用抗肿瘤坏死因子药物治疗（药物暴露 102.97 患者年）。作为外部对照组，从西班牙风湿病学会生物制品数据库中选择 35 例匹配倾向评分的非淀粉样患者。终点为肾脏反应和进展、抗肿瘤坏死因子持续率、患者生存和不良事件。

结果

在随访结束时，22 例患者中有 12 例（54.5%）观察到肾脏反应，36 例患者中有 6 例（17%）观察到肾脏进展。36 例患者中有 16 例（44%）肾脏淀粉样变性保持稳定。急性期反应物水平降低，但未达到正常水平。在经过 1、2、3 年和 4 年或以上后，淀粉样 A 淀粉样变性患者的抗肿瘤坏死因子药物持续率分别为 80%、80%、61%和 52%，与对照组相当。淀粉样 A 淀粉样变性病例的 5 年累积生存率为 90.6%，10 年生存率为 78.5%。在多变量 Cox 回归分析中，淀粉样变性的持续时间和抗肿瘤坏死因子治疗开始时蛋白尿的水平是治疗失败的独立预测因素，而蛋白尿水平是唯一预测死亡率的因素。两组的大多数不良事件相似，尽管淀粉样 A 淀粉样变性病例的感染次数是对照组的 3 倍。