Transplant Trial Watch

Effect of Optimized Immunosuppression (Including Rituximab) on Anti-Donor Alloresponses in Patients With Chronically Rejecting Renal Allografts

Shiu, K. Y., et al.

Frontiers in Immunology 2020 [record in progress]


Aims
The aim of this study was to report the results of an exploratory analysis that focused on investigating how B cell-depletion affects anti-donor immune responses, which was carried out by a previously conducted RCT (RituxiCAN-C4 study)

Interventions
Participants were randomized to the rituximab-treated group or the control group.

Participants
Kidney transplant recipients.

Outcomes
The outcomes of interest were the assessment of changes in the estimated glomerular filtration rate (eGFR), changes in donor specific antibody (DSA) human leukocyte antigen (HLA), and changes in circulating B cells.

Follow-up
3 years

CET Conclusions
This interesting paper reports the findings of the RituxiCAN-C4 study, a multicenter RCT investigating the role of rituximab in stabilizing function in renal transplant recipients with chronic rejection. At interim analysis the study was found to be underpowered and it was halted with no difference in clinical outcomes seen between arms. The paper therefore focuses on the exploratory analysis of B-cell subsets and the anti-donor immune response. Use of rituximab was associated with changes in regulatory B-cell subsets that may in fact be detrimental by preventing the B-cell mediated suppression of CD4+ anti-donor INF-gamma production. Whilst only exploratory, these findings are interesting and may help to explain the lack of efficacy seen in other studies of rituximab in this area. The study also highlights the challenges of running clinical trials in chronic rejection.

Jadad score
3

Data analysis
Per protocol analysis

Allocation concealment
Yes

Trial registration
EudraCT - 2006-002330-38; ClinicalTrials.gov - NCT00476164

Funding source
Non-industry funded