Alefacept combined with tacrolimus, mycophenolate mofetil and steroids in de novo kidney transplantation: A randomized controlled trial.
Rostaing L, Charpentier B, et al.American Journal of Transplantation 2013; 13(7):1724-33
Aims
To evaluate the efficacy and safety of alefacept compared with placebo when administered in combination with tacrolimus, mycophenolate mofetil (MMF) and corticosteroids in de novo kidney transplant recipients.
Interventions
Patients were administered with alefacept or placebo on the day of transplantation together with tacrolimus, MMF and corticosteroids. A second bolus was administered on day 3 with subsequent doses given weekly for 12 weeks.
Participants
112 adult patients suitable for primary renal transplantation or retransplantation.
Outcomes
The primary outcome included the incidence of biopsy confirmed acute T cell mediated rejection and the secondary outcomes included the incidence of antibody mediated rejection (AMR) or combined acute cellular rejection and AMR, patient survival, graft survival and graft loss.
Follow-up
6 months.
CET Conclusions
The supplementation of a standard immune suppression regimen with 3 months of Alefacept was not associated with a reduction in acute rejection episodes. The study was underpowered, with 63% power for a significance level of 0.1 (unusually). Most rejection episodes of rejection occurred during the first two weeks; Alefacept was associated with reduced CD-4+ memory T-cells from 3 weeks after surgery. There was no difference in CD-4+ naïve T-cell populations. There were no differences seen in the secondary outcomes including patient and graft survival, DGF and renal function. Adverse events were similar, except for malignancy rates, which were slightly higher in the Alefacept arm within the first six months (6% versus 1%, p=0.06). With longer follow up the difference in malignancy rates was no longer significant (6% versus 2%, p=0.17), so this association is unclear in this study.
Data analysis
Modified intention-to-treat analysis
Trial registration
EudraCT 2007-002092-14 and ClinicalTrials.gov – NCT00617604.