Eculizumab is FDA approved for the treatment of paroxysmal nocturnal haemoglobinuria, and for atypical HUS (aHUS). It has been used off-label in the treatment of TTP refractory to plasmapheresis.
In renal transplant recipients, it has been use, so far, for :
- Treatment of variety of complement/antibody-mediated microangiopathy syndromes such as atypical HUS.
- Severe antibody-mediated rejection (AMR)/Desensitization protocol;
- Patients with Antiphospholipid Antibody Syndrome (APS) and its rare subtype, Catastrophic Antiphospholidid Antibody Syndrome (CAPS);
-To reverse the potentially fatal effects of graft reperfusion injury
-To rescue Severe Accelerated AMR in ABO incompatible kidney transplant.
In lung transplant recipients to treat:
- aHUS in combined Lung-Kidney transplant.
- Hyperacute AMR
In Bone Marrow transplant patients it has been used to treat severe hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA).
Few important points:
- It is mandatory for patients to be immunized against meningococcus, hemophilus and pneumococci if not current due to the central role of the complement system in fighting infection. Nonetheless, meningococcal sepsis can be seen despite appropriate vaccination.
- Due to Eculizumab®’s mechanism of action, levels of antibodies-of any kind- are unchanged during its use; therefore researchers are still working to find a way to more accurately measure treatment response.
Take home messages:
-Vaccinate patients who potentially will need Eculizumab prior to transplant (at least 4 months).
- The duration of use is still unclear, but some patients with genetic abnormalities in complement activation may need life-long therapy.
-Adjust dose when using plasmapheresis (redosing after pheresis).
-You may need to do transplant kidney biopsies more frequently to follow up histology in cases of desensitization/AMR since currently there is no other more accurate way to find out if the therapy is working.
- Still no long-term safety data available. Since the variety of complement activation diseases is broad, is not going to be easy to do RTC, and on top of that, placebo arms will be mostly unacceptably in high risk for transplant patients. Nevertheless, large trials are warranted to prove its efficacy and long term safety… stay tune!
Figure from review from Zuber et al. Nat Rev Nephrol 2012
Adela Mattiazzi, MD