Belatacept是腎移植時有效的免疫抑制劑


  May 24, 2005 (西雅圖) - 2005年美國移植醫學大會,亦即第六屆美國移植外科醫學會與美國移植協會的聯合會議中,有一項研究發表指出,Belatacept是一目標導向性的免疫抑制劑,經試驗證實,對於腎臟移植者,是相等於傳統calcineurin抑制劑的另一項選擇。
  
  亞特蘭大城艾摩利大學的Chris Larsen醫師在會中表示,相較於環孢靈(cyclosporine),Balatacept顯示出相當程度的移植體存活率與急性排斥率;除了calcineurin抑制劑之外,Belatacept很有希望成為另一項的維護治療法。
  
  這是一項隨機性分配的第二期臨床試驗,一共有三組重新接受腎臟移植的患者參與,用以比較的免疫抑制劑為belatacept及傳統的環孢靈calcineurin抑制劑,該傳統藥物已知具有長期使用的毒性。
  
  所有的患者皆接受basiliximab的誘導療法,維護治療則為類固醇及mycophenolate mofetil治療;患者接受30分鐘的靜脈藥物注入,分別為環孢靈 A,或低劑量,或高劑量的belatacept。
  
  本研究一共有220位試驗患者,追蹤期為四年;患者們的標準風險都很低,平均年齡為45歲,大部分接受的是死者所捐贈的器官。
  
  第六個月的急性排斥現象為研究人員設定的主要試驗終點,以切片肌酸酐濃度是否超過0.5 mg/dL作為標準;次要終點則是第一年的移植體存活率。
  
  第12個月的急性排斥率,環孢靈組為8.2%,Belatacept中劑量組為6%,低劑量組為5.6%;這些數據之間並不具統計差異,所有的急性排斥現象皆發生在六個月之內。
  
  Larsen醫師表示,最重要的發現為慢性的異體腎臟病變風險,這項風險有了明顯的降低;環孢靈組中有44%有此症狀,低劑量及高劑量belatacept組則分別為20%及28%,與環孢靈組有著明顯差異;腎臟病變的降低應該可以改善移植體的存活期。
  
  Belatacept組的腎小球濾過率顯示出明顯的進步,這個結果可由單聚合顯影劑(iohexol)的血清排出率看出,也可由較低的血液膽固醇濃度及較低的平均血液收縮壓獲知。
  
  各組之間有著相似的巨大細胞病毒感染,環孢靈組有兩個癌症的案例,中劑量belatacept組有一例乳癌及三例淋巴增生病變;對此,Larsen表示,安全性是相當的。
  
  但是,俄亥俄大學的外科副教授Ginny Bumgardner醫師向Medscape表示,在於惡性腫瘤,一年之內,高劑量組就有4位患者罹患癌症,但這也是唯一較無急性排斥現象的一組,值得注意。
  
  必治妥施貴寶藥廠資助Larsen醫師的研究。

Belatacept, an Effective Immun

By Melissa Schorr
Medscape Medical News

May 24, 2005 (Seattle) — Belatacept, a targeted immunosuppressant drug, was an equivalent alternative to traditional calcineurin inhibitors among kidney transplant recipients, according to research presented here at the American Transplant Congress 2005: 6th Annual Joint Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation.

"In comparison to cyclosporine, belatacept showed comparable graft survival and acute rejection rates," Chris Larsen, MD, director of the Transplant Center at Emory University, Atlanta, Georgia, told attendees. "Belatacept shows promise as an alternative to calcineurin inhibitors as a primary maintenance therapy."

The randomized, phase 2, three-group study of de novo kidney transplants compared the drug belatacept with the traditional cyclosporine immunosuppressant calcineurin inhibitor, which holds known toxicities for long-term use.

All patients received basiliximab induction therapy, steroids, and mycophenolate mofetil maintenance therapy. Patients were either given cyclosporine A or either a high-intensity or low-intensity dosage of belatacept administered via a thirty-minute intravenous infusion.

The study enrolled 220 patients, who were followed up for four years. The patients were low to standard risk, an average age of 45 years, and most received cadaveric organs.

Researchers looked at acute rejection at six months as a primary endpoint, as measured by a rise of blood creatinine levels of more than 0.5 mg/dL confirmed by a biopsy. A secondary endpoint was graft survival at one year.

At twelve months, the rate of acute rejection was 8.2% in the cyclosporine group, 6% in the medium-intensity belatacept group, and 5.6% in the low-intensity group, which was not a statistically significant difference. All cases of acute rejection occurred before six months.

The most important finding, Dr. Larsen noted, was a decreased risk of chronic allograft nephropathy, which affected 44% of patients receiving cyclosporine, but only 20% of those taking low-intensity belatacept and 28% of those taking high-intensity belatacept, which was significant. The reduction in nephropathy might translate to improved graft survival, Dr. Larsen said.

Those receiving belatacept also showed improved preservation of glomerular filtration rate, as measured by iohexol plasma clearance, as well as slightly lower blood cholesterol level and mean systolic blood pressure.

The rate of cytomegalovirus infection was similar across groups. The cyclosporine group had two subsequent cases of cancer, while the medium-intensity belatacept group had a case of breast cancer and three cases of lymphoproliferative disorder. "Safety was comparable," Dr. Larsen said.

However, Ginny Bumgardner, MD, PhD, an associate professor of surgery at Ohio State University in Columbus, who moderated the panel, said she found the results on malignancies troubling. "Within one year, they have four patients with cancer in the high-intensity group, which is the only group that had an acute rejection advantage, which is concerning," Dr. Bumgardner told Medscape.

Dr. Larsen disclosed funding from Bristol-Myers Squibb.

ATC 2005: 6th Annual Joint Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation: Abstract 365. Presented May 23, 2005.

Reviewed by Gary D. Vogin, MD

    
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