Monoclonal and polyclonal antibody therapy for treating acute rejection in kidney transplant recipients: a systematic review of randomized trial data

Abstract

Background: We performed a comprehensive systematic review to determine the relative benefits and harms of widely used interventions used to treat acute rejection in kidney transplant recipients: monoclonal or polyclonal antibodies (Ab).

Methods: Databases and conference proceedings were searched for eligible trials in all languages, and two reviewers, working independently, assessed trials for eligibility and quality, and extracted data. Results are expressed as relative risk (RR) with 95% confidence intervals (CI).

Results: Twenty-one trials (49 reports) were identified. Most trials were small, incompletely reported, especially for potential harms, and did not define outcome measures adequately. Fourteen trials (965 patients) compared therapies for first rejection episodes (eight Ab versus steroid, two Ab versus another Ab, and four other comparisons) In treating first rejection, Ab was better than steroid in reversing rejection (RR 0.57; CI 0.38-0.87) and preventing graft loss (death-censored RR 0.74; CI 0.58-0.95) but there was no difference in preventing subsequent rejection (RR 0.67; CI 0.43-1.04) or death (RR 1.16; CI 0.57-2.33) at 1 year. Seven trials (422 patients) investigated Ab treatment of steroid-resistant rejection (four Ab vs. another Ab, one different doses Ab, one different formulation Ab, two other comparisons). There was no benefit of muromonab-CD3 over ATG or ALG in reversing rejection (RR 1.32; CI 0.33-5.28), preventing subsequent rejection (RR 0.99; CI 0.61-1.59) or preventing graft loss (RR 1.80; CI 0.29-11.23) or death (RR 0.39; CI 0.09-1.65).

Conclusions: Given the clinical problem caused by acute rejection, comparable data are sparse, and clinically important differences in outcomes between widely used interventions have not been excluded. Standardized reproducible outcome criteria are needed.