Polyclonal and monoclonal antibodies for treating acute rejection episodes in kidney transplant recipients.
Webster AC, Wu S, et al.Cochrane Database of Systematic Reviews 2017; 7: CD004756.
Aims
To conduct a systematic review to identify and summarise the evidence for the efficacy and adverse effects of using monoclonal or polyclonal antibodies to treat acute cellular or humoral rejection in kidney transplant recipients.
Interventions
The Cochrane Kidney and Transplant Specialised Register was searched up until 18th April 2017 for all randomized controlled trials where an antibody was compared to any other treatment with the aim of reversing acute rejection. The update was undertaken by five authors whereby at least two authors independently screened titles and abstracts for included studies, and data extraction was carried out independently by two authors using standard data extraction forms.
Participants
31 studies (76 reports, 1680 participants) were included in this systematic review which consisted of 11 new studies (18 reports, 346 participants) since a previous review in 2006.
Outcomes
The primary outcomes measured were reversal of acute rejection, time to reversal, recurrent rejection after treatment of rejection episode, and time to re-rejection. Secondary measured outcomes included graft loss, mortality, graft function, treatment failure necessitating a change in treatment, adverse effects, infection and incidence of malignancy.
Follow-up
12 and 18 months
CET Conclusions
This is a typically well conducted systematic review (Cochrane Renal Group) of the effectiveness of polyclonal and monoclonal antibodies for treating acute rejection episodes in kidney transplant recipients, and is an update of a review carried out in 2006. The study identified 31 studies with 1,680 patients included. The authors found that any antibody was better than steroid treatment for reversing the first acute cellular rejection episode and preventing graft loss but there was little or no difference in reversing steroid resistant rejection episodes. Polyclonal antibody treated patients were very likely to have the immediate reaction of fever chills and malaise, more so than those receiving steroid treatment. Antibody treatment thus was better than steroid treatment for reversing first acute cellular rejection and preventing graft loss but there was a high incidence of adverse effects. The main limitation of the review is that many of the included studies were performed during the cyclosporine/azathioprine era of kidney transplantation and therefore conclusions cannot necessarily be extrapolated to patients treated with more contemporary immunosuppressive regimens which include tacrolimus/mycophenolate or sirolimus. This is important as the incidence of acute rejection after kidney transplantation in the era of cyclosporine/tacrolimus has fallen quite markedly, as has the loss of kidneys from irreversible acute rejection. Thus, overall, the conclusions from this updated review are very similar to the original review and that any antibody used to treat acute rejection is probably more effective than steroids although I would have some doubt about that personally. Similarly, in reversing steroid resistant rejection there was little or no difference between different antibodies over twelve months. With respect to acute humoral rejection, there was no evidence that the use of antibody therapy conferred any additional benefits in terms of reversal of rejection or death or graft loss. The authors point out that there is a need for larger studies with standardised and reproducible outcome measurements in the treatment of acute rejection in recipients that are receiving contemporary immunosuppressive regimens.
Quality notes
Quality assessment not appropriate
Trial registration
None