Eculizumab
Eculizumab binds to complement component C5, thereby blocking its
cleavage and the subsequent formation of the C5b-C9 membrane attack
complex, the final common pathway effector of the complement system.
Approved indications for eculizumab are paroxysmal nocturnal
hemoglobinuria,
atypic hemolytic uremic syndrome (aHUS), myasthenia gravis and
neuromyelitis optica spectrum disorder. Besides the prevention and
treatment of aHUS and thrombotic microangiopathy (TMA), in organ
transplantation there are reports from its use for desensitization,
prevention and as supplement in the treatment of AMBR [30, 50-52].
Although these studies are too small to provide definitive conclusions
on the role of eculizumab in these situations, there is already an
example of how eculizumab concentration measurements combined with a
PK/PD model can be used for model-informed precision dosing in the
treatment of TMA in children undergoing HSCT [27].
Although no formal economic cost-benefit analysis was reported, for an
expensive drug like eculizumab it is worth to notice the remarks from
the authors that by using MIPD in their study each patient only received
the required therapy course which minimizes the risk of over treating
and reduces the clinical and financial burden of eculizumab therapy
[26]. The approach that was used in this study could also serve to
suggest how to tailor the application of eculizumab and other
biologicals in solid organ transplant recipients.