Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation.
Starling, R. C., Armstrong, B. et al. (2019).Journal of the American College of Cardiology 74(1): 36-51.
Aims
This study aimed to identify whether B cell depletion therapy would decrease the development of cardiac allograft vasculopathy.
Interventions
Patients were randomized to receive either rituximab 1000mg intravenous or placebo on days 3 and 12 post-heart transplantation.
Participants
163 heart transplant recipients (age: 18-75 years).
Outcomes
The primary outcome of this study was change in percent of atheroma volume (PAV) from baseline to one year. Secondary outcomes assessed included treated episodes of acute rejection, de novo anti-HLA antibodies and phenotypic differentiation of B cells.
Follow-up
1 year
CET Conclusions
This is a well written report of a good quality clinical trial in cardiac transplantation. The proposed hypothesis was that Rituximab treatment would prevent cardiac allograft vasculopathy compared to placebo following heart transplantation, by depleting B-cells and preventing antibody-mediated damage. Both the treatment arm and control arm received standard immune suppression post-operatively with tacrolimus, mycophenolate and tapering steroids (or alternatives at local investigators’ discretion). The study was adequately powered based on previous results. Unfortunately there are no details in the report of the method of randomisation or how blinding was maintained. The primary outcome was the mean change in percent atheroma volume at one year, as assessed by intra-vascular ultrasound. This outcome was significantly worse in the Rituximab arm, an unexpected outcome. There were no significant clinical outcomes associated with this (such as retransplantation, rejection or death) but the study was not powered for these. There was a similar proportion of patients who developed anti-HLA antibodies in both arms. It is speculated that certain B-cells have a regulatory function and the depletion with Rituximab can lead to other cell phenotypes filling the void. Whilst the authors would not discourage the use of Rituximab in cardiac transplantation to treat antibody mediated rejection, or PTLD, they agree that Rituximab should be avoided as induction therapy for non-sensitized cardiac transplant recipients.
Data analysis
Per protocol analysis
Trial registration
ClinicalTrials.gov - NCT01278745