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英夫利昔单抗剂量升级治疗难治性多发性大动脉炎的疗效和安全性:来自单中心队列的真实经验。

Effectiveness and safety of infliximab dose escalation in patients with refractory Takayasu arteritis: A real-life experience from a monocentric cohort.

机构信息

Unit of Immunology, Rheumatology, Allergy and Rare diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Vita-Salute San Raffaele University, Milan, Italy.

出版信息

Mod Rheumatol. 2022 Feb 28;32(2):406-412. doi: 10.1093/mr/roab012.

Abstract

OBJECTIVES

To evaluate effectiveness and safety of infliximab dose escalation in Takayasu arteritis (TAK) patients. To identify factors associated with refractoriness to standard-dose infliximab.

METHODS

Medical records of infliximab-treated TAK patients from a large single-centre observational cohort were reviewed. Infliximab therapy duration, concomitant therapies, and reasons for dose escalation and therapy suspension were evaluated. Occurrence of adverse events was recorded. A comparison between patients who maintained infliximab standard-dose and those who needed dose-escalation was performed. Factors associated with refractoriness to standard dose were analysed.

RESULTS

Forty-one patients were included. Starting infliximab dose was 5 mg/kg 6-weekly and 28 patients (68%) needed dose escalation. Persistence/recurrence of clinical symptoms was the most frequent reason for escalation. Median therapy duration was 39 (IQR, 26-61) months in the standard-dose group and 68 (38-87) months in the intensified-dose group. In the intensified-dose-group, infliximab was suspended in eight patients (29%) after a median of 38 (31-71) months, due to loss of response (n = 7) or patient's request (n = 1). Patients in the intensified-dose group had a higher number of relapses (3.4 vs 0.8 events/patient) and received a higher cumulative steroid dose (1.7 [1.6-2.3] vs 1.3 [1-1.6] g/month of prednisone). Three patients from the intensified-dose group had serious infections; one patient from the standard-dose group developed paradoxical psoriasis. At univariate analysis, age at diagnosis and age at infliximab start were associated with infliximab escalation.

CONCLUSION

In TAK, dose escalation is safe and allows to optimise infliximab durability in refractory patients. Younger patients seem to be more refractory to standard dosages.

摘要

目的

评估英夫利昔单抗剂量升级在大动脉炎(TAK)患者中的有效性和安全性。确定与标准剂量英夫利昔单抗治疗抵抗相关的因素。

方法

回顾了来自一个大型单中心观察队列的接受英夫利昔单抗治疗的 TAK 患者的病历。评估了英夫利昔单抗治疗持续时间、伴随治疗以及剂量升级和治疗暂停的原因。记录不良事件的发生情况。比较了维持英夫利昔单抗标准剂量和需要剂量升级的患者。分析了与标准剂量抵抗相关的因素。

结果

共纳入 41 例患者。起始英夫利昔单抗剂量为 5mg/kg,每 6 周 1 次,28 例(68%)需要剂量升级。临床症状持续/复发是升级的最常见原因。标准剂量组的中位治疗时间为 39(IQR,26-61)个月,强化剂量组为 68(38-87)个月。在强化剂量组中,8 例患者(29%)因失应答(n=7)或患者要求(n=1)在中位 38(31-71)个月后停用英夫利昔单抗。强化剂量组患者的复发次数更高(3.4 次 vs 0.8 次/患者),累积类固醇剂量更高(1.7[1.6-2.3] vs 1.3[1-1.6]g/月泼尼松)。强化剂量组中有 3 例患者发生严重感染,标准剂量组中有 1 例患者发生矛盾性银屑病。单因素分析显示,诊断时年龄和英夫利昔单抗起始时年龄与英夫利昔单抗升级相关。

结论

在 TAK 中,剂量升级是安全的,可以优化难治性患者英夫利昔单抗的耐久性。年轻患者似乎对标准剂量更具抵抗性。

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