Henderson Scott R, Copley Susan J, Pusey Charles D, Ind Philip W, Salama Alan D
From the Imperial College Kidney & Transplant Institute, Hammersmith Hospital, London, UK (SRH, CDP); Centre for Nephrology, Division of Medicine, University College London, London, UK (SRH, ADS); Radiology Department, Hammersmith Hospital, London, UK (SJC); Department of Respiratory Medicine, Hammersmith Hospital, London, UK (PWI).
Medicine (Baltimore). 2014 Dec;93(27):e229. doi: 10.1097/MD.0000000000000229.
Pulmonary nodule formation is a frequent feature of granulomatosis with polyangiitis (GPA). Traditional induction therapy includes methotrexate or cyclophosphamide, however, pulmonary nodules generally respond slower than vasculitic components of disease. Efficacy of rituximab (RTX) solely for the treatment of pulmonary nodules has not been assessed. In this observational cohort study, we report patient outcomes with RTX in GPA patients with pulmonary nodules who failed to achieve remission following conventional immunosuppression. Patients (n = 5) with persistent pulmonary nodules were identified from our clinic database and retrospectively evaluated. Systemic manifestations, inflammatory markers, disease activity, concurrent immunosuppression, and absolute B cell numbers were recorded pre-RTX and at 6 monthly intervals following treatment. Chest radiographs at each time point were scored by an experienced radiologist, blinded to clinical details. Five patients with GPA and PR3-ANCA were evaluated (2 male, 3 female), mean age 34 (22-52) years. Pulmonary nodules (median 4, range 2-6), with or without cavitation were present in all patients. RTX induced initial B cell depletion (<5 cells/μL) in all patients but re-population was observed in 3 patients. Repeated RTX treatment in these 3 and persistent B cell depletion in the whole cohort was associated with further significant radiological improvement. Radiographic scoring at each time interval showed reduction in both number of nodules (P = <0.0001) and largest nodule diameter (P = <0.0001) in all patients for at least 18 months following B cell depletion. In summary, RTX therapy induces resolution of pulmonary granulomatous inflammation in GPA following prolonged B cell depletion.
肺结节形成是肉芽肿性多血管炎(GPA)的常见特征。传统的诱导治疗包括甲氨蝶呤或环磷酰胺,然而,肺结节的反应通常比疾病的血管炎成分慢。利妥昔单抗(RTX)单独治疗肺结节的疗效尚未得到评估。在这项观察性队列研究中,我们报告了在接受传统免疫抑制治疗后未能缓解的GPA合并肺结节患者使用RTX的治疗结果。从我们的临床数据库中识别出5例持续性肺结节患者并进行回顾性评估。记录RTX治疗前及治疗后每6个月的全身表现、炎症标志物、疾病活动度、同时使用的免疫抑制剂以及绝对B细胞数量。每个时间点的胸部X光片由一位对临床细节不知情的经验丰富的放射科医生进行评分。评估了5例GPA和PR3-ANCA患者(2例男性,3例女性),平均年龄34岁(22 - 52岁)。所有患者均有肺结节(中位数4个,范围2 - 6个),有或无空洞。RTX使所有患者的B细胞最初耗竭(<5个细胞/μL),但3例患者出现了B细胞重新增殖。这3例患者重复使用RTX治疗以及整个队列持续的B细胞耗竭与进一步显著的影像学改善相关。在B细胞耗竭后的至少18个月内,每个时间间隔的影像学评分显示所有患者的结节数量(P = <0.0001)和最大结节直径(P = <0.0001)均有所减少。总之,RTX治疗在长期B细胞耗竭后可使GPA患者的肺肉芽肿性炎症消退。