Rheumatology Section, Imperial College London, Hammersmith Hospital, London, UK.
Clin Exp Rheumatol. 2014 May-Jun;32(3 Suppl 82):S11-8. Epub 2013 Sep 30.
We analysed a large cohort of patients with Takayasu arteritis, seeking robust clinical evidence for prolonged responses to tumour necrosis factor-α (TNF-α) and interleukin-6 receptor (IL-6R) antagonists in severe refractory disease.
Case notes from ninety-eight patients with Takayasu arteritis were retrospectively reviewed. Drug treatment, laboratory and serial non-invasive imaging data were analysed, and the Indian Takayasu arteritis activity (ITAS) and damage scores (TADs) calculated.
Nine patients were treated with biologic therapies. All had previously received high dose prednisolone and ≥1 conventional immunosuppressant. Five patients had failed cyclophosphamide. The patients prescribed biologics had more extensive arterial injury than the remainder of the cohort and persistent active disease (ITAS range 2-9, CRP 12-206 mg/L, TADs 3--1). Eight patients were prescribed anti-TNF-α therapy, three IL-6R blockade. The mean duration of anti-TNF-α treatment was 42 months (maximum 8 years). One patient developed new arterial stenoses while receiving anti-TNF-α and subsequently achieved disease remission with tocilizumab. Two patients have now demonstrated sustained responses to IL-6R inhibition at 19 and 20 months. Following introduction of biologic therapy, serial non-invasive imaging has revealed no significant progression in arterial injury. A significant fall in CRP (p<0.01), prednisolone dose (p<0.01) and ITAS (p<0.01) was observed, with no increase in TADs.
We report for the first time sustained responses to both anti-TNF-α and IL6R antagonists in refractory Takayasu arteritis. As 5/9 patients were cyclophosphamide non-responders, we propose that biologics should now be considered ahead of cyclophosphamide in these young patients.
我们分析了一组大样本的 Takayasu 动脉炎患者，旨在为严重难治性疾病中 TNF-α（肿瘤坏死因子-α）和 IL-6R（白细胞介素-6 受体）拮抗剂的长期疗效提供有力的临床证据。
回顾性分析了 98 例 Takayasu 动脉炎患者的病历。分析了药物治疗、实验室和连续的非侵入性影像学数据，并计算了印度 Takayasu 动脉炎活动（ITAS）和损伤评分（TADs）。
9 例患者接受了生物治疗。所有患者均曾接受过大剂量泼尼松龙和≥1 种传统免疫抑制剂治疗。5 例患者接受环磷酰胺治疗失败。接受生物制剂治疗的患者动脉损伤比其余患者更广泛，且疾病持续活动（ITAS 范围 2-9，CRP 12-206mg/L，TADs 3-1）。8 例患者接受了抗 TNF-α 治疗，3 例接受了 IL-6R 阻断治疗。抗 TNF-α 治疗的平均持续时间为 42 个月（最长 8 年）。1 例患者在接受抗 TNF-α治疗时出现新的动脉狭窄，随后接受托珠单抗治疗后疾病缓解。2 例患者在接受 IL-6R 抑制治疗后现已获得持续缓解，分别为 19 个月和 20 个月。生物治疗后，连续的非侵入性影像学检查显示动脉损伤无明显进展。CRP（p<0.01）、泼尼松龙剂量（p<0.01）和 ITAS（p<0.01）显著下降，而 TADs 无增加。
我们首次报道了难治性 Takayasu 动脉炎对 TNF-α 和 IL-6R 拮抗剂的持续缓解。由于 5/9 例患者对环磷酰胺无反应，我们建议在这些年轻患者中，生物制剂应优先于环磷酰胺。
