Alemtuzumab as induction therapy in renal transplantation: differing results from systematic reviews.

By: John O'Callaghan | Posted on: 3rd January 2013

Re: Alemtuzumab induction in renal transplantation: A meta-analysis and systemic review. Zhang X, Huang H, Han S, Fu S, Wang L. Transpl Immunol. 2012 Oct;27(2-3):63-8

A recent systematic review and meta-analysis has been published in Transplant Immunology. The review by Zhang et al assesses the evidence for the use of Alemtuzumab as induction therapy in renal transplantation. It is compared to “traditional antibodies” including Rabbit Antithymocyte Globulin (rATG) and Interleukin-2 Receptor Antibodies (IL2RAs). The authors conclude that Alemtuzumab is superior to traditional antibodies in the prevention of acute rejection. Last year Morgan et al published a review of this topic, reaching slightly different conclusions to Zhang et al.

Zhang et al concluded that Alemtuzumab reduced acute rejection in comparison with “traditional antibodies” which included a combination of agents. They found specifically that Alemtuzumab reduced acute rejection compared to rATG but did not have enough studies to compare Alemtuzumab to IL2RAs alone.

In contrast to this, we concluded that Alemtuzumab reduces rejection events in comparison with IL2RAs (RR=0.54, p<0.01) but not in comparison with rATG (RR=0.79, p=0.28).

There are three key reasons why these differing conclusions were presented by the two papers:

  1. Zhang et al combined results from studies comparing a variety of agents to Alemtuzumab. Given the different mechanisms of action we did not do this and only compared it to each class separately.
  2. Our method of analysis was facilitated by inclusion of data from studies that Zhang et al did not include. One of these studies is currently unpublished but additional data was kindly provided by the authors on request.
  3. We used data from the later report of one study, rather than the earlier report used by Zhang et al. The later report had longer follow-up and included more patients (180 versus 77).

The differences in methodology lead to rather different conclusions between the two reviews. In order to minimize biases in reviews it is important to identify unpublished studies and to request data from these if possible. Requesting additional data from the authors of published studies also allows reviewers to take extra steps in making the best use of study data.


Comments

    Simon Knight says:

    This is a great example of how differing inclusion criteria and methodologies can have a large impact on the conclusions drawn by a systematic review. By combining studies in an inappropriate way and failing to identify and include “in progress” trials, Zhang et al came to the conclusion that Campath is superior to rATG, a finding that is not supported by the available data!


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