Does adding rituximab to IVIg and plasmapheresis improve outcome of antibody mediated rejection? One year results of the RITUX-ERAH study.
In transplant and nephrology, the use of rituximab has been increasing. Numerous papers have included it as a treatment for antibody mediated rejection (AMR) in the transplant literature; however, there are essentially no placebo controlled RCT’s proving its efficacy. Dr. Sautent presented data from a randomized controlled French study comparing the addition of rituximab to plasma exchange and IVIg to placebo in patients with AMR. The results may surprise you.
Adult deceased donor kidney transplant recipients with biopsy proven AMR were treated with at least 3 sessions of plasmapheresis followed by 100 mg/kg of IVIg, then 2 grams per Kg of IVIg on treatment day number five with the addition of either 375 mg/m2 of rituximab or placebo. Primary endpoint was the combination of graft loss or absence of improvement in kidney function on day 12 of treatment. Kidney function and histology at later follow up was included as secondary endpoints. 40 patients were randomized with 19 in the placebo arm and 21 in the rituximab arm. The groups were similar at baseline. So here is the kicker – primary endpoint was met in 52.6% of the rituximab group and 57.9% of the placebo group – basically there was no difference. There was also no difference in kidney function, degree of proteinuria at 12 months post treatment. Even histology was the same. The only trend towards a difference was a slight decrease in donor specific HLA antibody in the rituximab group.
During the session audience members brought up criticisms such as a potential decrease in rituximab’s efficacy due to co-administration with high dose IVIg; however, Dr. Sautenet fired back stating that there was good B cell depletion in their study. And only time can tell what the reduction in DSA means for long term outcome. Regardless of limitations, this is an important study. Rituximab is a potent immunosuppressant – one with well documented infectious side effects. This study shows us just how important performing placebo controlled trials really are. Hopefully we will see more collaborative well structured trials like this in the future.
Post written by Dr. Vinay Nair, eAJKD Advisory Board member.
Check out all of eAJKD’s coverage of the 2013 American Transplant Congress.