Belatacept treatment for two yr after liver transplantation is not associated with operational tolerance.

Clinical Transplantation 2015; 29(1): 85-89.

Aims
To evaluate liver and kidney function of belatacept treated liver transplant (LT) patients two years after the end of treatment (EOT). EOT was defined as the date of the next scheduled belatacept infusion after study termination as this time point indicates the loss of sufficient pharmacological efficacy of belatacept.

Interventions
At EOT participants were switched to Mycophenolate mofetil (MMF) monotherapy (1000 mg twice daily). Patients had previously been randomized to receive one of five regimens; Tacrolimus (TAC) only, TAC + MMF, belatacept high dose (HD) + MMF + basiliximab, belatacept HD + MMF, or belatacept low dose (LD) + MMF.

Participants
8 adult recipients of their first LT aged 18–70 years still enrolled in the belatacept trial* at the time of termination.

Outcomes
Outcomes measured were liver and kidney function.

Follow-up
2 years

CET Conclusions
In this study from Vienna, the authors report the outcome of eight patients who had been enrolled in the liver transplant belatacept trial which was discontinued during its long-term extension because of an unacceptable death and morbidity rate in the belatacept arm. Following discontinuation of belatacept, these four patients were switched to monotherapy with mycophenolate (2g/day) but this led to an unacceptable level of rejection and they were started on a calcineurin inhibitor (CNI). This in turn led to a marked deterioration in renal function which had been far superior in the belatacept treated patients at the time of termination compared to that in the CNI arm. The authors were hoping that in the patients who had belatacept discontinued that operational tolerance might be achieved but there was no evidence whatsoever of that. Thus, the authors conclude that their data in a small number of patients which, of course, is a limitation of the study, showed no obvious immuno-modulatory effect in liver transplant recipients of belatacept. This is in contrast to other studies where some patients with a liver transplant have become operationally tolerant after discontinuing immunosuppression.

Jadad score
3

Data analysis
Modified intention-to-treat analysis

Allocation concealment
Yes

Quality notes
Previously reported as *Klintmalm et al. Belatacept-Based Immunosuppression in De Novo Liver Transplant Recipients: 1-Year Experience From a Phase II Randomized Study. Am J Transplant. 2014 Aug; 14(8):1817-27

Trial registration
None

Funding source
Industry funded