Patient profile of indications for treatment of generalized myasthenia gravis with complement C5 inhibitors

Abstract

The pathophysiology of neuromuscular junction (NMJ) diseases can be divided into the following three categories.

1) Number, spatial distribution, and NMJ morphology of acetylcholine receptors (AChRs)

2) Number of release quanta from nerve endings

3) Cholinesterase activity

The pathology of myasthenia gravis (MG) corresponds to the above–mentioned 1). It is already known that AChR antibodies play a role in this mechanism. In the NMJ of the patients with MG, AChR antibodies are deeply involved in I) the destruction of postsynaptic membranes via complement activation, II) the promotion of AChR disintegration, and III) the direct inhibition of AChR function. Complement is necessary for the composition of the pathology caused by autoantibodies in MG. Therefore, complement can be a target for the treatment of MG, and treatment targeting complement is also attracting attention in both central and peripheral nervous system diseases. In this article, we will consider the current status of complement–targeted therapeutics for generalized MG and which cases are indicated for anti–complement agents.

As with congenital complement deficiency, the use of anti–complement drugs increases the risk of infection with encapsulated bacteria, therefore it is important to take measures to prevent side effects. It is also important to be aware that the C5 gene polymorphism p.Arg885His, which is a cause of non–response, is present in approximately 3.5% of Japanese people, but as this is outside the main topic of this article, we will not discuss it in detail.