C5 complement inhibitors: mechanisms of action, indications, risk of infections, and prevention strategies

Abstract

The C5 complement inhibitors eculizumab and ravulizumab are two monoclonal antibodies used to treat myasthenia gravis (MG), neuromyelitis optica spectrum disorder (NMOSD), atypical hemolytic uremic syndrome (aHUS), thrombotic microangiopathy (TMA), and paroxysmal nocturnal hemoglobinuria (PNH). These monoclonal antibodies target specific parts of the immune system and are therefore called targeted therapies. Their function is to block the C5 portion of complement, preventing its cleavage into C5a and C5b. The C5a portion has an inflammatory and prothrombotic effect; the C5b portion forms the terminal membrane attack complex (C5b-C9) (1, 2). In this way, inflammation that causes damage to the optic nerve, spinal cord and brainstem in NMOSD is stopped, destruction of the postsynaptic membrane is prevented in patients with MG, and hemolysis in PNH and thrombotic microangiopathy in HUS are controlled.