Clinical Efficacy and Safety of Eculizumab for Treating Myasthenia Gravis

Abstract

Myasthenia gravis (MG) is an autoimmune disease primarily mediated by acetylcholine receptor antibodies (AChR-Ab), cellular immune dependence, and complement system involvement. Since the AChR on the postsynaptic membrane is destroyed by an immune attack, sufficient endplate potential cannot be generated, resulting in the development of a synaptic transmission disorder at the neuromuscular junction and in muscle weakness. The role of the complement system in MG has been demonstrated in animal models and clinical tests, and it has been determined that complement inhibition in patients with MG can prevent disease induction and reverse its progression. Eculizumab is a humanized monoclonal antibody that inhibits the cleavage of complement protein C5 and prevents autoimmune damage; additionally, it has received subsequent approval by the Federal Drug Administration of the United States for MG treatment. However, various concerns regarding the use of eculizumab persist. In this review, we have discussed the treatment time, cost effectiveness, long-term efficacy, and tolerability of eculizumab for MG treatment. We have also summarized historical information and have presented perspectives on this new therapeutic modality.

Practical Management for Use of Eculizumab in the Treatment of Severe, Refractory, Non-Thymomatous, AChR + Generalized Myasthenia Gravis: A Systematic Review

“…Physiologically, several molecules, including decay-accelerating factor (CD55) and C1 esterase inhibitor, act to prevent inappropriate complement activation directed towards self cells. 12,13 The Role of Complement in MG Preclinical Data…”

Molecular Therapy in Myasthenia Gravis

“…44 Eculizumab does not have any role in reducing antibody production and acts only on the complement cascade. 45 The risk of meningococcaemia is another potential problem with eculizumab, and patients receiving this drug should be vaccinated against Neisseria meningitidis 2 weeks prior to starting eculizumab. 46 The beneficial effects of eculizumab compared with placebo led to its approval by the FDA for its use in refractory, AChR antibody-positive MG. 47 An open-label extension of the REGAIN trial also demonstrated a significant reduction in rates of exacerbation of MG, rates of MG-related hospitalization and increase in global clinical improvement scores.…”

The Management of Generalized Myasthenia Gravis in Adults: New Biological Therapies

“…Other side effects reported include diarrhea, upper respiratory infection, and arthritis. Notably, no cases of meningococcal infection were reported, possibly due to vaccination prior to enrollment in the study [6]. The therapies administered to patients at the beginning of eculizumab administration were IVIg, prednisone, pyridostigmine, mycophenolate, and azathioprine.…”

“…Additionally, eculizumab seemed to present a favorable benefit-risk profile in pregnant patients and no adverse reactions in either the patient or the infant. Notably, a few patients were recruited, and the findings should be considered cautiously [6,7].…”