Blog entry by Arif Khwaja

Anyone in the world

An excellent randomised controlled trial is published in this weeks New England Journal of Medicine, from the INTAC study group, based at the University of Alabama, Birmingham, looking at the role of Alemtuzumab induction and steroid sparing immunosuppression. Alemtuzumab is a humanised  anti-CD52 monoclonal antibody targeting both B and T lymphocytes. Increasingly a number of centres are using Alemtuzumab induction to enable steroid free immunosuppression. This RCT compared Alemtuzumab to Basiliximab for low risk recipients and Alemtuzumab to ATG for high risk recipients in patients on Tacrolimus and MMF with steroids being stopped after one week. High risk was defined as second allograft, black race or panel reactivity greater than 20%. Alemtuzumab was given as a single dose of 30mg. With respect to the 139 high risk patients there was no difference in biopsy proven acute rejection between the ATG group and Alemtuzumab with rejection rates of 18% vs 15%. in the low risk group the rate of biopsy-confirmed acute rejection in low-risk patients was lower with alemtuzumab than with basiliximab : 12 months (5% vs. 17%, P<0.001) and at  3 years(10% vs. 22%, P=0.003)There are some slightly concerning results however. Whilst the overall rejection rate was lower with Alemtuzumab the late rejection rate (between 12 and 36 months  was higher). Further lymphopaemia persisted in Alemtuzumab group for well over 2 years. Overall the Alemtuzumab group had  a slightly (and significantly) higher rate of cancer. Furthermore whilst the infection rate was lower than ATG it was higher when compared to Basiliximab. 

 
In summary these data show that Alemtuzumab induction offers an excellent way of avoiding steroids whilst achieving low rates of rejection. The higher rates of infections is a cause for concern in low risk patients. However amongst high risk patients the risk profile is broadly similiar to ATG whilst being perhaps easier to administer - a single 30mg dose.
As ever with transplantation the key question is whether this induction protocol will translate into better long term outcomes and better graft survival but for the time being this trial is a significant advance in the road to steroid free immunosuppression. See http://blogs.nejm.org/now/index.php/alemtuzumab-induction-in-renal-transplantation/2011/05/18/
[ Modified: Thursday, 1 January 1970, 1:00 AM ]