Korswagen L A, Bartelds G M, Krieckaert C L M, Turkstra F, Nurmohamed M T, van Schaardenburg D, Wijbrandts C A, Tak P P, Lems W F, Dijkmans B A C, van Vugt R M, Wolbink G J
VU University Medical Center, Amsterdam, The Netherlands.
Arthritis Rheum. 2011 Apr;63(4):877-83. doi: 10.1002/art.30209.
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.
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.
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).
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.
我们观察了3例在使用阿达木单抗治疗期间发生严重静脉和动脉血栓栓塞事件的患者，其中2例患有类风湿关节炎（RA），1例患有银屑病关节炎。所有3例患者均检测到抗阿达木单抗抗体。我们进行这项研究以确定抗阿达木单抗抗体的产生是否与阿达木单抗治疗期间的血栓栓塞事件相关。
对272例连续纳入的接受阿达木单抗治疗的RA患者的前瞻性队列进行回顾性搜索（对抗阿达木单抗抗体状态进行盲法处理）以查找血栓栓塞事件。计算发病率并使用Cox回归估计风险比（HR）。所有索引患者均不是该队列的一部分。
272例患者中有76例（28%）检测到抗阿达木单抗抗体。发现8例血栓栓塞事件，其中4例发生在有抗阿达木单抗抗体的患者中。有抗阿达木单抗抗体的患者发病率为26.9/1000人年，无这些抗体的患者发病率为8.4/1000人年（HR 3.8 [95%置信区间0.9 - 15.3]，P = 0.064）。在对随访时间、年龄、体重指数、红细胞沉降率和既往血栓栓塞事件进行调整后，HR为7.6（95%置信区间1.3 - 45.1）（P = 0.025）。
这些发现表明，在阿达木单抗治疗期间，有抗阿达木单抗抗体的患者发生静脉和动脉血栓栓塞事件的几率高于无抗阿达木单抗抗体的患者。患者数量相对较少；因此，必须在其他队列中进行验证。
