Tacrolimus/MMF可安全有效的用於心臟移植


  April 8, 2005(費城) - 在國際心臟與肺臟移植協會的第25屆年會上有一項發表,根據一大型、多臨床中心、隨機分配的控制性臨床試驗結果顯示,在心臟移植上,相較於其他常用的免疫抑制法,Tacrolimus及mycophenolate mofetil(MMF)的合併使用可以獲致較少的排斥現象,副作用的情況也會比較輕微。
  
  ISHLT的前任總裁,同時也是加州大學洛杉磯分校醫療主任的Jon W. Kobashigawa醫師發表指出,和tacrolimus/sirolimus及cyclosporin/MMF相比較,Tacrolimus/MMF似乎是最有效的組合,因為這個方法的排斥現象及副作用最少。
  
  Kobashigawa表示,Tacrolimus/MMF較之cyclosporin/MMF組,有較少的患者因為排斥而需要治療。
  
  Kobashigawa再次表示,Tacrolimus/sirolimus組也顯現出較低的排斥率,但這個組合卻關連著更多的副作用,最明顯的就是腎功能不全及高血脂症;這些都是比較常見且明顯的問題,也可能只是學習的過程;根據研究人員對Medscape所作的表示,或許在和sirolimus並用時,Tacrolimus的劑量應該降低。
  
  Tacrolimus的日劑量為2到4mg,分兩次投予,前三個月的目標濃度為10到20ng/mL,4到12個月則為5到15ng/mL。
  
  本研究納入了43位心臟移植的患者,手術在美國的28個醫院內進行,期間為2001年11月至2003年6月;患者們大部分為男性(每組73%以上)及白種人(80%以上)。
  
  在第12個月時,因器官排斥而需要接受治療者,Tacrolimus/MMF組為35%,Tacrolimun/sirolimus組為42.1%,Cyclosporin/MMF組則為59.6%;細胞排斥的降低現象亦有類似的趨勢(ISHLT 3A級或更高),血液動力異常的狀況也有類似的傾向(tacrolimus/MM,F24.3%;tacrolimus/sirolimus,22.4%;cyclosporine/MMF,33.3%)。
  
  據Kobashigawa指出,該項研究並未對各組的存活率作評估。
  
  Tacrolimus/sirolimus組有著最低的病毒感染率(8.3%),其次為cyclosporin/MMF組(20.2%),最後為tacrolimus/MMF組(20.4%);這個項目包含巨大細胞病毒感染。
  
  不論是否接受降血脂治療,Cyclosporin/MMF組的高血脂症是三組中最高的;另外,Tacrolimus/MMF組有著較好的腎功能。
  
  Kobashigawa向Medscape表示,整體而言,這項試驗的結果顯示,Tacrolimus及MMF合併使用,具有良好的效果及安全性;但是,確定的是,不論是研究人員或醫師們,皆應根據他們的經驗及自信程度來決定治療的方式,同時也應該預測可能的負面反應。
  
  Kobashigawa最後表示,我想這三種組合並未被下定論,必須要完成更大型的研究才能得知;也許,Tacrolimus在和如sirolimus的增殖訊號抑制劑合用時,應該考慮到劑量的調整。
  
  Kobashigawa醫師的研究由Fujisawa Healthcare, Inc,所贊助,該公司為tacrolimus (Prograf)的製造者。
  
  ISHLT 第25屆年會:摘要61;4月7日發表。

Tacrolimus/MMF Safe, More Effe

By
Medscape Medical News

Andrew Bowser

April 8, 2005 (Philadelphia) — Among cardiac transplant recipients, the combination of tacrolimus and mycophenolate mofetil (MMF) results in fewer rejections and has a more favorable adverse effect profile compared with other commonly used immunosuppressive regimens, according to final results of a large, multicenter, randomized controlled trial described here at the 25th annual meeting of the International Society for Heart and Lung Transplantation (ISHLT).

The tacrolimus/MMF combination "appears to be the most effective regimen for lowest treated rejection incidence and least side effect profile" compared with tacrolimus/sirolimus and cyclosporine/MMF, Jon W. Kobashigawa, MD, medical director of the University of California, Los Angeles, Heart Transplant Program and a past president of ISHLT, said during his presentation.

The results showed significantly fewer rejections requiring treatment in the tacrolimus/MMF group compared with the cyclosporine/MMF group, he said.

The tacrolimus/sirolimus group also had a significantly lower incidence of treated rejections, but that combination seemed to be associated with more adverse effects — most notably, renal insufficiency and hyperlipidemia. "These are commonly noted issues, but it may just be a learning curve [issue] as well," the researcher said in an interview with Medscape. "Perhaps we should be using lower doses of tacrolimus when it's used in combination with sirolimus."

Tacrolimus was dosed at 2 to 4 mg/day in two divided doses, with a target level of 10 to 20 ng/mL in the first three months, then 5 to 15 ng/mL for months 4 through 12.

The study included 343 de novo cardiac transplant recipients enrolled at 28 U.S. sites between November 2001 and June 2003. Subjects were mostly male (73% or more in each study group) and white (80% or more).

At 12 months, incidence of organ rejection requiring treatment was 35% in the tacrolimus/MMF group, 42.1% in the tacrolimus/sirolimus group, and 59.6% in the cyclosporine/MMF group (P < .001). There was also a trend toward less cellular rejection (ISHLT grade 3A or greater) and less hemodynamic compromise requiring treatment (24.3% for tacrolimus/MMF, 22.4% for tacrolimus/sirolimus, and 33.3% for cyclosporine/MMF; P = .056).

The study was not powered to determine a survival difference between groups, according to Dr. Kobashigawa.

Viral infections were significantly less common in the tacrolimus/sirolimus group (8.3%) compared with the tacrolimus/MMF group (20.4%) and the cyclosporine/MMF group (20.2%; P = .016), including significantly fewer cytomegalovirus infections (P = .009).

Despite treatment with lipid-lowering medications, there were more cases of hyperlipidemia in the cyclosporine/MMF group than in either tacrolimus group, according to the presenter. In addition, the tacrolimus/MMF group had significantly better renal function.

Taken together, these results "suggest tacrolimus/MMF is a good and effective combination to use," Dr. Kobashigawa told Medscape, "although certainly, one must use regimens based on their own program's experience and confidence range, and also, the expected adverse events that investigators, or physicians in general, are used to and, notably, can treat.

"I don't think the jury is in, to say the least, on all three drug combinations," he added. "Larger studies have to be done, and perhaps modification of the [tacrolimus] dose when it is with a proliferation signal inhibitor such as sirolimus."

Dr. Kobashigawa disclosed research support from Fujisawa Healthcare, Inc, the maker of tacrolimus (Prograf).

ISHLT 25th Annual Meeting and Scientific Sessions: Abstract 61. Presented April 7, 2005.

Reviewed by Gary D. Vogin, MD

Andrew Bowser is a freelance writer for Medscape.

    
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