Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica
Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica
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DOI：
10.1002/acr.21750
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发表时间：
2012-11-01
影响因子：
4.7
通讯作者：
Stone, J. H.
中科院分区：
文献类型：
--
作者：
Unizony, S.;Arias-Urdaneta, L.;Stone, J. H.
目的巨细胞动脉炎（GCA）、大动脉炎（TA）和风湿性多肌痛（PMR）患者白细胞介素6（IL-6）通路表达上调。我们回顾性评估了10例复发/难治性GCA、TA或PMR患者接受托珠单抗（TCZ）治疗的结局。方法GCA（n = 7）、TA（n = 2）和PMR（n = 1）患者接受TCZ治疗。7例受试者至少1种二线药物治疗失败。评估的结果是疾病活动的症状，炎症标志物，能够逐渐减少糖皮质激素，和横截面imaging时表示clinically.Results的平均随访时间为27个月（范围1660个月），这个队列诊断。患者接受TCZ治疗的平均时间为7.8个月（范围为412个月）。TCZ治疗前，患者平均每年发作2.4次。所有患者在TCZ治疗期间进入并维持临床缓解。TCZ开始治疗前后泼尼松的平均日剂量分别为20.8 mg/d（范围734.3 mg/d）和4.1 mg/d（范围010.7 mg/d）（P = 0.0001）。平均红细胞沉降率从41.5 mm/h（范围1168 mm/h）降至7 mm/h（范围2.211.3 mm/h; P = 0.0001）。TCZ的不良反应包括轻度中性粒细胞减少（n = 4）和转氨酶升高（n = 4）。1例患者在TCZ停药后2个月发作。尸检1例术后心肌梗死择期手术后死亡，发现持续性血管炎的大，中型artery.Conclusion TCZ治疗导致难治性/复发性GCA，TA，或PMR患者的临床和血清学改善。1例表现出实质性缓解的患者尸检时显示持续性大血管炎，需要在更大规模的研究中进行仔细审查。
Objective The interleukin-6 pathway is up-regulated in giant cell arteritis (GCA), Takayasu arteritis (TA), and polymyalgia rheumatica (PMR). We retrospectively assessed the outcomes of 10 patients with relapsing/refractory GCA, TA, or PMR treated with tocilizumab (TCZ).Methods Patients with GCA (n = 7), TA (n = 2), and PMR (n = 1) received TCZ. Seven subjects had failed at least 1 second-line agent. The outcomes evaluated were symptoms of disease activity, inflammatory markers, ability to taper glucocorticoids, and cross-sectional imaging when indicated clinically.Results The mean followup time of this cohort since diagnosis was 27 months (range 1660 months). The patients were treated with TCZ for a mean period of 7.8 months (range 412 months). Before TCZ therapy, the patients experienced an average of 2.4 flares/year. All patients entered and maintained clinical remission during TCZ therapy. The mean daily prednisone dosages before and after TCZ initiation were 20.8 mg/day (range 734.3 mg/day) and 4.1 mg/day (range 010.7 mg/day), respectively (P = 0.0001). The mean erythrocyte sedimentation rate declined from 41.5 mm/hour (range 1168 mm/hour) to 7 mm/hour (range 2.211.3 mm/hour; P = 0.0001). The adverse effects of TCZ included mild neutropenia (n = 4) and transaminitis (n = 4). One patient flared 2 months after TCZ discontinuation. An autopsy on 1 patient who died from a postoperative myocardial infarction following elective surgery revealed persistent vasculitis of large and medium-sized arteries.Conclusion TCZ therapy led to clinical and serologic improvement in patients with refractory/relapsing GCA, TA, or PMR. The demonstration of persistent large-vessel vasculitis at autopsy of 1 patient who had shown a substantial response requires close scrutiny in larger studies.