托法替布治疗白塞病心脏大血管受累的疗效及安全性

目的探索托法替布(tofacitinib,TOF)治疗难治性血管白塞病的疗效和安全性。方法分析北京协和医院2018年5月至2020年2月5例使用托法替布治疗难治性白塞病大血管和心瓣膜受累患者的临床资料。记录联合应用托法替布前后糖皮质激素和免疫抑制剂种类和剂量、红细胞沉降率(erythrocyte sedimentation rate,ESR)和超敏C反应蛋白(high-sensitivity C-reactive protein,hsCRP)水平、影像学变化。结果5例患者(男性3例,女性2例),平均年龄(42.8±13.0)岁,中位病程72(60,264)月。大血管受累3例,均有多发动脉狭窄和闭塞,2例同时存在腹主动脉假性动脉瘤,1例并发静脉血栓;主动脉和心瓣膜受累2例,主要表现为升主动脉及主动脉根部扩张导致的重度主动脉瓣关闭不全;5例均有血管介入/心脏瓣膜手术史,其中3例有多次手术史。使用托法替布前,5例患者经激素联合多种免疫抑制剂治疗疗效不佳,病情进展,新发大血管病变或术后并发症。联合应用托法替布5~10 mg/d,随访(10.6±7.7)个月,5例患者的临床症状均有所改善,无新发血管病变,主动脉和瓣膜受累的2例患者病情平稳,心功能恢复。炎症指标显著下降,ESR由21(7,101)mm/h降至5(1,11)mm/h(P=0.028),hsCRP由21(1.24,67)mg/L降至0.5(0.32,1.3)mg/L(P=0.018)。泼尼松剂量由8.5(5~10)mg/d减至6.5(2.5~10)mg/d,环磷酰胺均得以减量,4例实现托法替布减量。无明显药物不良反应。结论对难治性大血管和心瓣膜受累的白塞病,联合使用托法替布有助于稳定病情,降低炎症反应,减少术后并发症和激素用量,耐受性较好。

Tofacitinib for the treatment of refractory vascular Behcet'disease

Objective To explore the effectiveness and safety of tofacitinib for the treatment of refractory vascular Behcet’ disease. Methods We retrospectively analyzed the clinical data of five patients with refractory vascular Behcet’ disease treated with tofacitinib from May 2018 to February 2020 in our hospital. We recorded the doses of glucocorticoids and immunosuppressive agents, erythrocyte sedimentation rate(ESR), high-sensitivity C-reactive protein(hsCRP) levels, and imaging changes before and after combined treatment with tofacitinib. Results Of the five patients enrolled(three males and two females), the mean age was(42.8±13.0)years, the median duration of disease was 72(60, 264) months. Three patients presented with large vessel involvement, with multiple arterial stenosis and occlusions. Two of them had aortic pseudoaneurysms, and one had contemporary venous involvement.Aortic root dilation and severe aortic valve insufficiency were documented in two cases. All the patients had a history of vascular intervention or surgery on heart valves, and three of them had multiple operations. Prior to tofacitinib treatment, all five patients were treated with corticosteroids and multiple immunosuppressants. However, they displayed poor response with evidence of disease progression and postoperative complications. Combination therapy with tofacitinib 5-10 mg/d was initiated while maintaining background treatment. After a median follow-up of(10.6±7.7)months, all the patients achieved clinical improvement.Vascular lesions were radiologically stable, and no progressive aneurysm or post-operative perivalvular leakage was observed. The ESR and hsCRP levels decreased significantly 21(7, 101)mm/1 h vs 5(1, 11)mm/1 h(P=0.028), and 21(1.24, 67)mg/L to 0.5(0.32, 1.3)mg/L(P=0.018), respectively. The dose of prednisone was tapered from 8.5(5~10)mg/d to 6.5(2.5~10)mg/d]. The dose of cyclophosphamide and tofacitinib were also decreased. No prominent adverse reactions were observed. Conclusions Our study suggests that tofacitinib is effective for the treatment of refractory vascular Behcet’ disease. Combination therapy with tofacitinib may help reduce inflammation, decrease postoperative complications, and taper the dose of corticosteroids or immunosuppressants.