原文

译文

Arthritis & Rheumatism DOI: 10.1002/art.30209

Venous and arterial thromboembolic events in adalimumab-treated patients with antiadalimumab antibodies: A case series and cohort study

1.       L. A. Korswagen^1,†,

2.       G. M. Bartelds^2,†,

3.       C. L. M. Krieckaert²,

4.       F. Turkstra²,

5.       M. T. Nurmohamed²,

6.       D. van Schaardenburg²,

7.       C. A. Wijbrandts³,

8.       P. P. Tak³,

9.       W. F. Lems⁴,

10.   B. A. C. Dijkmans^4,‡,

11.   R. M. van Vugt¹,

12.   G. J. Wolbink^5,*,§

Abstract

Objective

We observed 3 patients who developed severe venous and arterial thromboembolic events during treatment with adalimumab, 2 of whom had rheumatoid arthritis (RA) and 1 of whom had psoriatic arthritis. Antiadalimumab antibodies were detected in all 3 patients. We undertook this study to determine whether the development of antiadalimumab antibodies was associated with thromboembolic events during adalimumab treatment.

Methods

A retrospective search (with blinding with regard to antiadalimumab antibody status) for thromboembolic events was performed in a prospective cohort of 272 consecutively included adalimumab-treated RA patients. Incidence rates were calculated and hazard ratios (HRs) were estimated using Cox regression. None of the index patients were part of the cohort.

Results

Antiadalimumab antibodies were detected in 76 of 272 patients (28%). Eight thromboembolic events were found, 4 of which had occurred in patients with antiadalimumab antibodies. The incidence rate was 26.9/1,000 person-years for patients with antiadalimumab antibodies and 8.4/1,000 person-years for patients without those antibodies (HR 3.8 [95% confidence interval 0.9–15.3], P = 0.064). After adjustment for duration of followup, age, body mass index, erythrocyte sedimentation rate, and prior thromboembolic events, the HR was 7.6 (95% confidence interval 1.3–45.1) (P = 0.025).

Conclusion

These findings suggest that the occurrence of venous and arterial thromboembolic events during adalimumab treatment is higher in patients with antiadalimumab antibodies than in those without antiadalimumab antibodies. Patient numbers were relatively small; therefore, validation in other cohorts is mandatory.

抗阿达木单抗的抗体可能与阿达木单抗治疗过程中静脉和动脉血栓事件相关

Korswagen LA, et al. Arthritis Rheum. 2011;63:877-83.

目的: 我们观察到3例接受阿达木单抗治疗的患者发生严重静脉和动脉血栓事件，其中有2例RA和1例银屑病关节炎(PsA)。检测发现这3例患者均已出现抗阿达木的抗体。本研究旨在探究抗阿达木的抗体是否与治疗过程中的血栓事件有关联。

方法: 在顺序收治的、接受阿达木单抗治疗的272例RA患者中，回顾性筛查血栓事件(临床评估者不知晓病人的抗抗体状态)。计算不良事件发生率，并用Cox回顾分析得出风险比值(HR)。前述索引病人并不包括在这个队列中。

结果: 272例病人中抗阿达木抗体阳性者有76例(28%)。发现8起血栓事件，其中4起发生于抗抗体阳性者。抗阿达木抗体阳性者的血栓事件发生率为26.9/1000病人年，而抗抗体阴性者的血栓发生率为8.4/1000病人年(HR: 3.8, 95%CI: 0.9～15.3, P = 0.064)。在校正了随访时长、年龄、体质指数(BMI)、血沉和之前已发生血栓事件之后，相应的HR为7.6(95%CI: 1.3–45.1; P = 0.025)。

结论: 这些发现提示，在接受阿达木单抗治疗过程中，出现抗阿达木抗体的RA病人发生血栓的风险高于那些抗抗体阴性者。本研究的病例数相对较小，故需在未来进行验证。