Basiliximab加Tacrolimus可降低肝移植排斥並增加存活率


  Sept. 24, 2004 - 根據一項預期研究結果顯示,Basiliximab 加入tacrolimus基的抑制免疫力的療法,對降低細胞急性排斥(ACR)的影響是有效的,且不增加副作用及感染,並增進在原位肝移植(OLTx)後免於細胞急性排斥的存活率;該項研究結果刊載於9月27日的移植雜誌。
  
  美國外科醫師學會會員,美國賓州費城湯瑪斯傑佛遜大學附屬醫院肝臟移植及肝膽管外科部門主管Ignazio R. Marino醫師及其同事指出,使用單克隆抗體來預防細胞急性排斥,可以避免很多由使用多克隆抗體所導致的副作用。
  
  Basiliximab是一種混成式單克隆抗體用來對抗白細胞介素2受體(CD25)的α鏈,已經被廣泛的評估當作腎臟移植病人的誘導化學治療,更常用和拒絕反應抑止藥合併使用。
  
  為了探討basiliximab和拒絕反應抑止藥合併使用療法之功效及安全性,研究人員分析了50位原位肝移植手術(47位屍肝捐贈,3位活肝捐贈,平均年紀為49.78歲,35名男性),其中有21位病人有c型肝炎相關的肝硬化。
  
  所有病患在肝灌注檢查及移植後的第四天期間給予basiliximab 20-mg劑量,然後給予tacrolimus 0.15 mg/kg/day(目標最低濃度10-15 ng/mL),及甲基強體松龍(Methylprednisolone)的逐漸減弱療法。
  
  病人三年精確的存活率為88%,移植存活率為75%;九位病人移植物喪失,實施再移植;四位病患因為晚期植入失敗死亡;12位病患發生敗血症,其中兩位死亡。
  
  在追蹤期間(799.89 ± 257.37 天),44位病患(88%)沒有細胞急性排斥ACR,5位病患(10%)有一次ACR,及1位病患(2%)有三次ACR,平均ACR發生率為每月0.15 ± 0.21次,在前三個月無拒絕機率為75%。
  
  研究人員表示,一份法國近期的研究顯示,三年ACR發生率12%和一年排斥率38%,和匹茲堡大學所作一年的排斥率45.2%,當我們研究結果和美國及歐洲多中心FK506肝臟研究組織比較時,這其中的差異甚至更大;他們指出,美國及歐洲使用類固醇和tacrolimus的個別一年排斥率為68% 及 40.5%。
  
  在陽性C型肝炎病患中,在追蹤期的三年內,有九位(42%)C型肝炎復發;研究人員表示,和匹茲堡大學所作研究為(42% - 53%),Basiliximab 加入抑制免疫力的療法,在我們的研究中不會增加C型肝炎復發率。
  
  研究人員強調,這是別具意義的,因為C型肝炎復發病患顯示較高的晚期感染影響,感染大部分由於病原體伴隨削弱的細胞免疫功能所產生。
  
  Basiliximab有好的耐受性及沒有注入副作用,沒有巨細胞病毒感染及移植後淋巴增生疾病。
  
  本研究證實basiliximab對減少ACR發生次數及增加原位肝移植的成功率是有效的,加入basiliximab是安全的,且不會增加副作用及感染的發生率。
  
  研究人員建議,對於這項有潛力的療法,放棄抑制免疫力藥物使用的研究是必要的,基於在病患中觀察到的樂觀結果,我們相信,對tacrolimus and basiliximab之非膽固醇抑制免疫力療法用於成年之肝接受者,特別是C型肝炎復發病患是恰當的。

Basiliximab Plus Tacrolimus Re

By Yael Waknine
Medscape Medical News

Sept. 24, 2004 — Basiliximab in a tacrolimus-based immunosuppressive regimen is effective in reducing incidences of acute cellular rejection (ACR) and improving ACR-free survival after orthotopic liver transplantation (OLTx), without increasing the incidence of adverse events or infections, according to the results of a prospective study published in the Sept. 27 issue of Transplantation, posted online Sept. 22.

"Induction with monoclonal antibodies for prevention of ACR may avoid many of the adverse events associated with polyclonal antibodies," writes Ignazio R. Marino, MD, FACS, director of the Division of Liver Transplantation and Hepatobiliary Surgery at Thomas Jefferson University Hospital in Philadelphia, Pennsylvania, and colleagues. "Basiliximab, a chimeric monoclonal antibody directed against the α-chain of the interleukin 2 receptor (CD25), has been extensively evaluated as an induction therapy for kidney transplant patients, more frequently in combination with a cyclosporine-based regimen."

To explore the efficacy and safety of basiliximab in combination with a cyclosporine-based regimen, the investigators analyzed 50 consecutive OLTx procedures (47 cadaveric donors, 3 living donors; mean age, 49.78 years; 35 men). Of these, 21 patients had hepatitis C virus (HCV)-related cirrhosis.

A 20-mg dose of basiliximab was administered to all patients at liver perfusion and on day 4 posttransplantation, followed by 0.15 mg/kg/day tacrolimus (target trough level, 10-15 ng/mL) and a tapered regimen of methylprednisolone.

The actuarial patient survival rate at three years was 88%, with a 75% rate of graft survival. Graft loss occurred in nine patients (18%), resulting in retransplantation. Four deaths occurred due to late graft failure. Two deaths resulted from sepsis that occurred in 12 patients (24%).

During the follow-up period (799.89 ± 257.37 days), 44 patients (88%) had no ACR episodes, five patients (10%) had one episode, and one patient (2%) had three episodes. Mean ACR rate was 0.15 ± 0.21 episodes per month. Rejection-free probability was 75% within the first three months.

According to the authors, the 12% three-year ACR rate compares favorably with the 38% one-year rejection rate recently reported in a French study, as well as the 45.2% one-year rejection rate reported in a study based at the University of Pittsburgh. "The difference is even more dramatic when our results are compared to the U.S. and European multicenter FK506 liver study groups, in which the 1-year rejection rates with steroids and tacrolimus were 68% and 40.5%, respectively," they point out.

Among the HCV-positive patients, nine (42%) developed HCV recurrence within the three-year follow-up period. According to the authors, this result compares favorably with the results of the University of Pittsburgh trial (42% - 53%). "[T]he addition of basiliximab to baseline immunosuppression in our study did not increase the HCV recurrence rate," the authors note. "This is particularly relevant because patients with recurrent HCV hepatitis show a higher incidence of late-occurring infections, mostly as a result of pathogens associated with depressed cell-mediated immunity."

Basiliximab was well-tolerated and no infusion adverse effects were observed. No cytomegalovirus infections or posttransplant lymphoproliferative disorders occurred.

"This study demonstrated that basiliximab...was effective in reducing the number of ACR episodes and increasing the probability of remaining rejection-free after OLTx, which could potentially result in improved long-term outcomes," the authors write, adding that basiliximab was safe and did not increase the adverse events profile or rate of infection.

"Investigation of the potential of this regimen for allowing later weaning from maintenance immunosuppressants is needed," the authors suggest. "Based on the favorable outcome observed in our patient population reported here, we believe that it would be appropriate to test a steroid-free immunosuppressive regimen based on tacrolimus and basiliximab in adult liver recipients...with particular attention to HCV recurrence in this subgroup of patients."

The authors report no pertinent financial disclosures.

Transplantation. 2004;78(6):886-891

Reviewed by Gary D. Vogin, MD

    
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