De Vita S, Quartuccio L, Isola M, Mazzaro C, Scaini P, Lenzi M, Campanini M, Naclerio C, Tavoni A, Pietrogrande M, Ferri C, Mascia M T, Masolini P, Zabotti A, Maset M, Roccatello D, Zignego A L, Pioltelli P, Gabrielli A, Filippini D, Perrella O, Migliaresi S, Galli M, Bombardieri S, Monti G
Clinic of Rheumatology, AO Universitaria Santa Maria della Misericordia, and University of Udine, Udine, Italy.
Arthritis Rheum. 2012 Mar;64(3):843-53. doi: 10.1002/art.34331.
To conduct a long-term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV).
Fifty-nine patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated. Patients were randomized to the non-RTX group (to receive conventional treatment, consisting of 1 of the following 3: glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid dosage when possible, and with a second course of RTX at relapse). Patients in the non-RTX group who did not respond to treatment could be switched to the RTX group. Study duration was 24 months.
Survival of treatment at 12 months (i.e., the proportion of patients who continued taking their initial therapy), the primary end point, was statistically higher in the RTX group (64.3% versus 3.5% [P < 0.0001]), as well as at 3 months (92.9% versus 13.8% [P < 0.0001]), 6 months (71.4% versus 3.5% [P < 0.0001]), and 24 months (60.7% versus 3.5% [P < 0.0001]). The Birmingham Vasculitis Activity Score decreased only after treatment with RTX (from a mean ± SD of 11.9 ± 5.4 at baseline to 7.1 ± 5.7 at month 2; P < 0.001) up to month 24 (4.4 ± 4.6; P < 0.0001). RTX appeared to be superior therapy for all 3 target organ manifestations, and it was as effective as conventional therapy. The median duration of response to RTX was 18 months. Overall, RTX treatment was well tolerated.
RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.
开展一项长期、前瞻性、随机对照试验，评估利妥昔单抗（RTX）治疗重度混合性冷球蛋白血症或冷球蛋白血症性血管炎（CV）的效果。
纳入59例患有CV以及相关皮肤溃疡、活动性肾小球肾炎或难治性周围神经病变的患者。对于同时合并丙型肝炎病毒（HCV）感染的CV患者，此前使用抗病毒药物治疗HCV感染失败或未予治疗。患者被随机分为非RTX组（接受以下3种常规治疗之一：糖皮质激素；硫唑嘌呤或环磷酰胺；或血浆置换）或RTX组（接受2次每次1 g的输注，尽可能降低糖皮质激素剂量，复发时进行第二个疗程的RTX治疗）。非RTX组中对治疗无反应的患者可转至RTX组。研究持续时间为24个月。
主要终点即12个月时的治疗生存率（即继续接受初始治疗的患者比例），RTX组在统计学上更高（64.3%对3.5%[P<0.0001]），3个月时（92.9%对13.8%[P<0.0001]）、6个月时（71.4%对3.5%[P<0.0001]）以及24个月时（60.7%对3.5%[P<0.
