中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2011年
8期
516-519
,共4页
黄洪锋%吴建永%寿张飞%张建国%成秀举%刘光军%申屠建中%吴丽花%李晶%周波%陈江华
黃洪鋒%吳建永%壽張飛%張建國%成秀舉%劉光軍%申屠建中%吳麗花%李晶%週波%陳江華
황홍봉%오건영%수장비%장건국%성수거%류광군%신도건중%오려화%리정%주파%진강화
肾移植%临床试验,Ⅰ期%人源化抗CD3单抗%安全性
腎移植%臨床試驗,Ⅰ期%人源化抗CD3單抗%安全性
신이식%림상시험,Ⅰ기%인원화항CD3단항%안전성
Kidney transplantation%Clinical trials,phase Ⅰ%Humanized anti-CD3 mAb%Safety
目的 研究肾移植受者体内应用人源化抗CD3单克隆抗体(OKT3)注射液单次剂量递增给药后的短期和长期安全性.方法 2008年6-12月,共29例肾功能稳定的尸体肾移植受者入选该研究.每位受试者按入组顺序随机分至2.5 mg(n=9)、5.0 mg(n=10)、10.0 mg(n=10)3个剂量组,并于移植术后7～14 d内接受相应剂量的OKT3单次给药.同时选取同期未参加试验的30例肾移植受者作为对照组.所有患者至少随访2年,随访期间监测肝功能、肾功能、血常规等指标,并观察有无其他不良事件.结果 各剂量组受试者在给药后48 h内,出现低热(7/29)、畏寒(4/29)、肝功能损害(2/29)、上呼吸道感染(1/29)和头痛(1/29),未出现明显的首剂效应,其余的不良反应轻微,发生率与剂量无关.随访期间内,试验组和对照组2-年人/肾长期存活率分别为100%/100%和100%/97%;移植肾活检证实的急性排斥发生率分别为6.9%(2/29)和10.0%(3/30),肺部感染发生率分别为10.3%(3/29)和13.3%(4/30).术后1周及3、6、12、24个月监测血肌酐值显示,两组差异均无统计学意义(均P＞0.05).结论 人源化OKT3不同剂量单次给药在肾移植受者体内安全性良好,其有望成为一种抗排斥能力强、毒副作用较小的免疫抑制剂.
目的 研究腎移植受者體內應用人源化抗CD3單剋隆抗體(OKT3)註射液單次劑量遞增給藥後的短期和長期安全性.方法 2008年6-12月,共29例腎功能穩定的尸體腎移植受者入選該研究.每位受試者按入組順序隨機分至2.5 mg(n=9)、5.0 mg(n=10)、10.0 mg(n=10)3箇劑量組,併于移植術後7～14 d內接受相應劑量的OKT3單次給藥.同時選取同期未參加試驗的30例腎移植受者作為對照組.所有患者至少隨訪2年,隨訪期間鑑測肝功能、腎功能、血常規等指標,併觀察有無其他不良事件.結果 各劑量組受試者在給藥後48 h內,齣現低熱(7/29)、畏寒(4/29)、肝功能損害(2/29)、上呼吸道感染(1/29)和頭痛(1/29),未齣現明顯的首劑效應,其餘的不良反應輕微,髮生率與劑量無關.隨訪期間內,試驗組和對照組2-年人/腎長期存活率分彆為100%/100%和100%/97%;移植腎活檢證實的急性排斥髮生率分彆為6.9%(2/29)和10.0%(3/30),肺部感染髮生率分彆為10.3%(3/29)和13.3%(4/30).術後1週及3、6、12、24箇月鑑測血肌酐值顯示,兩組差異均無統計學意義(均P＞0.05).結論 人源化OKT3不同劑量單次給藥在腎移植受者體內安全性良好,其有望成為一種抗排斥能力彊、毒副作用較小的免疫抑製劑.
목적 연구신이식수자체내응용인원화항CD3단극륭항체(OKT3)주사액단차제량체증급약후적단기화장기안전성.방법 2008년6-12월,공29례신공능은정적시체신이식수자입선해연구.매위수시자안입조순서수궤분지2.5 mg(n=9)、5.0 mg(n=10)、10.0 mg(n=10)3개제량조,병우이식술후7～14 d내접수상응제량적OKT3단차급약.동시선취동기미삼가시험적30례신이식수자작위대조조.소유환자지소수방2년,수방기간감측간공능、신공능、혈상규등지표,병관찰유무기타불량사건.결과 각제량조수시자재급약후48 h내,출현저열(7/29)、외한(4/29)、간공능손해(2/29)、상호흡도감염(1/29)화두통(1/29),미출현명현적수제효응,기여적불량반응경미,발생솔여제량무관.수방기간내,시험조화대조조2-년인/신장기존활솔분별위100%/100%화100%/97%;이식신활검증실적급성배척발생솔분별위6.9%(2/29)화10.0%(3/30),폐부감염발생솔분별위10.3%(3/29)화13.3%(4/30).술후1주급3、6、12、24개월감측혈기항치현시,량조차이균무통계학의의(균P＞0.05).결론 인원화OKT3불동제량단차급약재신이식수자체내안전성량호,기유망성위일충항배척능력강、독부작용교소적면역억제제.
Objective To evaluate short-term and long-term safety of using single-dose escalation of recombinant humanized anti-CD3 monoclonal antibody (OKT3) in kidney transplantation recipients.Methods A total of 29 recipients of cadaveric kidney transplant from June 2008 to December 2008 were sequently assigned to receive single-dose intravenous injection of OKT3 with different doses of 2. 5 mg( n =9) , 5.0 mg (n = 10) and 10. 0 mg (n = 10) at Days 7 - 14 post-operation. Meanwhile, a control group was established by selecting kidney transplant recipients, who did not participate in the trial in the same period.All patients were followed up for at least 2 years. During this period, liver function, kidney function,hemoglobin and other biochemical indicators were monitored and adverse events recorded over time. Results No obvious first dose effect was observed,except low heat (7/29), chills (4/29) , mild liver damage (2/29) , upper respiratory tract infection and headache (1/29) across all doses. Other adverse reactions were mild, unrelated with doses. The 2-year patients/ grafts survival rates of treatment goup and control group were 100% / 100%, and 100% / 97%, respectively. The incidence of acute rejection confirmed by renal biopsy was 6. 9% (2/29) and 10. 0% (3/30) in treatment group and control group, respectively. The incidence of lung infection was 10. 3% ( 3/29 ) and 13.3% ( 4/30 ), respectively. The values of serum creatinine at 1 week and 3, 6, 12, 24 months showed no statistically significance in two groups ( all P ＞0. 05). Conclusion It is safe to use single-shot OKT3 intravenously in kidney transplant recipients. The recombinant humanized OKT3 may be an effective immunosuppressive agent with milder toxicity for solid organ transplantation.
