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比较类风湿关节炎患者在先前 TNF 拮抗剂治疗失败后转换为替代 TNF 拮抗剂与转换为利妥昔单抗的疗效:MIRAR 研究。

Comparative effectiveness of switching to alternative tumour necrosis factor (TNF) antagonists versus switching to rituximab in patients with rheumatoid arthritis who failed previous TNF antagonists: the MIRAR Study.

机构信息

Department of Rheumatology Unit, Hospital Clinico Universitario, Santiago de Compostela, Santiago, Spain.

出版信息

Ann Rheum Dis. 2012 Nov;71(11):1861-4. doi: 10.1136/annrheumdis-2012-201324. Epub 2012 Jun 26.

Abstract

OBJECTIVE

To compare the effectiveness of switching to rituximab (RTX) with switching to alternative tumour necrosis factor (TNF) antagonists in patients with rheumatoid arthritis (RA) failing on TNF antagonists.

METHODS

A multicentre prospective 3-year observational study was performed in patients with RA treated with RTX or an alternative TNF antagonist. The baseline 28-joint disease activity score (DAS28) and Health Assessment Questionnaire (HAQ) score were compared with 6, 9 and 12 month values, adjusting for propensity score quintiles. Propensity scores were estimated for each patient using logistic regression with treatment as the dependent variable and baseline prior number of TNFs >1, years from diagnosis >5, extra-articular manifestations, previous toxicity, use of ≥2 disease-modifying antirheumatic drugs, age and sex as independent variables.

RESULTS

1124 patients were treated with either RTX (n=591, 52.6%) or alternative TNF antagonists (n=533, 47.4%). RTX-treated patients had longer disease duration (p=0.0001), larger numbers of previous TNF antagonists (p<0.0001) and tender and swollen joints (p<0.0001). There was no significant difference in the reduction in DAS28 at 6, 9 and 12 months between RTX-treated patients and those treated with TNF antagonists. However, the reduction in DAS28 was significantly different between RTX-treated patients and adalimumab/infliximab-treated patients (p=0.001 and p=0.05, respectively). There was a marginally significant difference at any time period in the proportion of patients achieving an improvement in the HAQ score of >0.22 (p=0.06).

CONCLUSIONS

Optimal treatment for patients with RA failing on treatment with TNF antagonists may include RTX. This study suggests that the improvement in DAS28 is larger in patients treated with RTX than in those treated with monoclonal anti-TNF agents.

摘要

目的

比较在肿瘤坏死因子(TNF)拮抗剂治疗失败的类风湿关节炎(RA)患者中,转换为利妥昔单抗(RTX)与转换为其他 TNF 拮抗剂的疗效。

方法

对接受 RTX 或其他 TNF 拮抗剂治疗的 RA 患者进行了一项多中心前瞻性 3 年观察性研究。比较了基线 28 关节疾病活动度评分(DAS28)和健康评估问卷(HAQ)评分与 6、9 和 12 个月时的值,调整了倾向评分五分位数。使用逻辑回归对每位患者的倾向评分进行了估计,将治疗作为因变量,将基线时 TNF 治疗次数>1、诊断后时间>5 年、关节外表现、既往毒性、使用≥2 种疾病修饰抗风湿药物、年龄和性别作为自变量。

结果

1124 例患者接受了 RTX(n=591,52.6%)或其他 TNF 拮抗剂(n=533,47.4%)治疗。RTX 治疗组患者的疾病持续时间更长(p=0.0001),使用 TNF 拮抗剂的次数更多(p<0.0001),且压痛关节和肿胀关节更多(p<0.0001)。RTX 治疗组与 TNF 拮抗剂治疗组在 6、9 和 12 个月时 DAS28 的降低无显著差异。然而,RTX 治疗组与阿达木单抗/英夫利昔单抗治疗组之间 DAS28 的降低存在显著差异(p=0.001 和 p=0.05)。在任何时间段,HAQ 评分改善>0.22 的患者比例均存在显著差异(p=0.06)。

结论

对于 TNF 拮抗剂治疗失败的 RA 患者,最佳治疗方法可能包括 RTX。本研究表明,与使用单克隆抗 TNF 药物治疗的患者相比,RTX 治疗的患者 DAS28 改善更大。

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