Venhoff N, Proft F, Schulze-Koops H, Holle J, Voll R E, Iking-Konert C, Jacobi A M, Henes J, Unger L, Kneitz O, Dörner T, Thiel J
Vaskulitiszentrum Freiburg, Klinik für Rheumatologie und Klinische Immunologie, Department Innere Medizin, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Hugstetterstraße 55, 79106, Freiburg, Deutschland.
Sektion Rheumatologie und Klinische Immunologie, Medizinische Klinik IV, Klinikum der Universität München, München, Deutschland.
Z Rheumatol. 2018 Feb;77(1):21-27. doi: 10.1007/s00393-017-0315-3.
To evaluate the clinical efficacy and safety of off-label biological therapies in patients with ANCA-associated vasculitis (AAV) and non-ANCA-associated small-vessel vasculitis (nAAV) in clinical practice.
The German Registry in Autoimmune Diseases 2 (GRAID2) is a national, retrospective, non-interventional, multicentre observational study (August 2006 until December 2013) on patients with autoimmune diseases refractory to standard immunosuppressive therapy treated with off-label biologicals.
Data from 64 patients (20.6% of all GRAID2 patients) were collected: 54 patients (84.4%) had ANCA-associated vasculitis (AAV) and 10 patients (15.6%) had non-ANCA-associated small-vessel vasculitis (nAAV). Of the AAV patients, 96.3% were treated off-label with rituximab (RTX) and 3.7% with tumor necrosis factor alpha (TNFα)-inhibitors. Of patients with nAAV, 30% were treated with RTX, 60% with TNFα-inhibitors, and 10% with tocilizumab. The main reasons for off-label biological treatment in AAV patients were pulmonary, renal, or ear, nose, and throat involvement. These manifestations clearly improved in most patients after off-label biological therapy was initiated. Daily glucocorticoid dosage could be reduced. The off-label biological therapy was generally well tolerated. In AAV patients, 4.18 severe infections per 100 patient years were observed. There was one death in the nAAV group caused by fungal infection and ileus. A correlation between this fatality and RTX treatment was regarded as possible.
Safety and efficacy of off-label RTX-treatment in AAV-patients could be assessed in the GRAID2 data. Results point to good efficacy and safety of RTX in this special patient cohort and support the approval of RTX for AAV induction therapy.
评估在临床实践中，标签外生物疗法用于抗中性粒细胞胞浆抗体相关性血管炎（AAV）和非抗中性粒细胞胞浆抗体相关性小血管炎（nAAV）患者的临床疗效和安全性。
德国自身免疫性疾病注册研究2（GRAID2）是一项全国性、回顾性、非干预性、多中心观察性研究（2006年8月至2013年12月），研究对象为对标准免疫抑制治疗难治的自身免疫性疾病患者，采用标签外生物制剂进行治疗。
收集了64例患者的数据（占所有GRAID2患者的20.6%）：54例患者（84.4%）患有抗中性粒细胞胞浆抗体相关性血管炎（AAV），10例患者（15.6%）患有非抗中性粒细胞胞浆抗体相关性小血管炎（nAAV）。在AAV患者中，96.3%接受了标签外利妥昔单抗（RTX）治疗，3.7%接受了肿瘤坏死因子α（TNFα）抑制剂治疗。在nAAV患者中，30%接受了RTX治疗，60%接受了TNFα抑制剂治疗，10%接受了托珠单抗治疗。AAV患者接受标签外生物治疗的主要原因是肺部、肾脏或耳鼻喉受累。在开始标签外生物治疗后，大多数患者的这些表现明显改善。每日糖皮质激素剂量可以减少。标签外生物治疗总体耐受性良好。在AAV患者中，每100患者年观察到4.18例严重感染。nAAV组有1例因真菌感染和肠梗阻死亡。认为该死亡与RTX治疗之间可能存在关联。
在GRAID2数据中可以评估AAV患者标签外RTX治疗的安全性和疗效。结果表明RTX在这一特殊患者群体中具有良好的疗效和安全性，并支持RTX用于AAV诱导治疗的获批。
