Falsey Ann R, Koval Christine, DeVincenzo John P, Walsh Edward E
University of Rochester School of Medicine and Rochester General Hospital, Rochester, NY, USA.
Cleveland Clinic, Cleveland, OH, USA.
Transpl Infect Dis. 2017 Apr;19(2). doi: 10.1111/tid.12657. Epub 2017 Mar 6.
Respiratory syncytial virus (RSV) may cause fatal lower respiratory tract infection (LRTI) in immunocompromised patients. Ribavirin with or without standard intravenous immunoglobulin (IVIG) is frequently given although efficacy is debated. Infusion of IVIG with high levels of neutralizing antibody against RSV may offer benefit in these patients.
RI-001 contains standardized levels of high-titer anti-RSV neutralizing antibody and was provided for compassionate use to 15 patients with RSV LRTI who either failed conventional therapy or had significant risk of progression. Patients were treated on day 1 with RI-001 1500 mg/kg, followed 2 days later with 750 mg/kg. Pre- and post-infusion sera were measured for RSV neutralizing antibody. Patient data were analyzed for safety related to infusion of RI-001, and clinical outcomes.
Patients ranged in age from 2 months to 71 years and 80% had hematologic malignancy or were bone marrow or hematopoietic stem cell transplant recipients. Administration was well tolerated. Pre-infusion neutralizing titers ranged from 51 to 1765 geometric mean titer (mean 646±519) and all patients demonstrated at least a 4-fold rise (mean 6410±4470) 5-10 days post infusion. Eleven of 15 improved and were discharged from the hospital. Days from positive RSV test to RI-001 treatment was shorter in survivors compared to non-survivors (4.4±2.8 vs. 20.3±21.0 days, P=.02).
Administration of RI-001 was well tolerated and resulted in significant increases in serum neutralizing antibody titers to RSV. Our data suggest that early identification of RSV and treatment with RI-001 may offer benefit.
呼吸道合胞病毒（RSV）可在免疫功能低下的患者中引起致命的下呼吸道感染（LRTI）。尽管疗效存在争议，但利巴韦林联合或不联合标准静脉注射免疫球蛋白（IVIG）仍经常使用。输注具有高水平抗RSV中和抗体的IVIG可能对这些患者有益。
RI-001含有标准化水平的高滴度抗RSV中和抗体，被用于同情用药，给予15例患有RSV LRTI且常规治疗失败或有显著进展风险的患者。患者在第1天接受1500mg/kg的RI-001治疗，2天后接受750mg/kg的治疗。在输注前后检测血清中的RSV中和抗体。分析患者数据以了解与RI-001输注相关的安全性和临床结果。
患者年龄从2个月至71岁不等，80%患有血液系统恶性肿瘤或为骨髓或造血干细胞移植受者。给药耐受性良好。输注前中和滴度范围为51至1765几何平均滴度（平均646±519），所有患者在输注后5-10天均显示至少4倍的升高（平均6410±4470）。15例患者中有11例病情改善并出院。与非幸存者相比，幸存者从RSV检测阳性到接受RI-001治疗的天数更短（4.4±2.8天对20.3±21.0天，P=0.02）。
RI-001的给药耐受性良好，并导致血清中针对RSV的中和抗体滴度显著增加。我们的数据表明，早期识别RSV并用RI-001治疗可能有益。
