By Lauren Taylor from In The Cloud Copy

Myasthenia gravis is an autoimmune condition characterized by muscle weakness and fatigue of muscles that are under the patient’s voluntary control. This weakness and fatigue is caused by a breakdown in the communication that normally takes place between the muscles and the nerves. While there is no cure, patients are usually treated with various medications including cholinesterase inhibitors, corticosteroids, and immunosuppressants. Patients may also require IV therapy of plasmapheresis, intravenous immunoglobulin (IVIg), and monoclonal antibodies.

While many patients recover with the above mentioned pharmacologic therapies, about 10-15% of patients have refractory disease for a few reasons, including intolerable immunosuppressive therapy (IST) related events, inability to lower IST doses without relapse in disease, or regular IVIg or plasma exchange therapies. Patients experiencing refractory disease will experience symptoms that affect breathing, talking, swallowing, walking, and other activities. This greatly affects the patient’s quality of life.

Pharmacologic Advances for Patients with Refractory Disease

Eculizumab is a medication in testing stages with potential to improve quality of life for those living with refractory myasthenia gravis. This medication, developed by Alexion Pharmaceuticals, works by binding to the terminal complement protein C5, ultimately inhibiting enzymatic cleavage of C5. This inhibition prevents signaling of C5a-induced chemotaxis of proinflammatory cells and the formation of C5b-induced membrane attack complex. Preventing these will ultimately stop the membrane damage that occurs at the neuromuscular junction in these patients with refractory myasthenia gravis.

Study Methodology, Dosing, and Patient Assessments

The study took place over a six-month period. There were 62 patients in the control group that received eculizumab and 63 patients who received the placebo. Eligible participants were 18 years of age or older and had confirmed refractory myasthenia gravis. They had to have received at least two or more ISTs or at least one IST and required chronic IVIg or plasma therapy in the previous 12 months. Of the 30 patients who discontinued the study, seven of them had to discontinue due to adverse events.

Study participants were either given IV eculizumab or a placebo for a 26-week period. Two assessments were completed on patients, one patient-reported questionnaire, MG-ADL, consists of eight items assessing the impact of muscle weakness on a patient’s activities of daily living. The other questionnaire, a physician-reported questionnaire, called the QMG, has 13 items measuring muscle strength through ocular assessment, bulbar assessment, respiratory assessment and gross motor assessment. These were performed weekly from weeks 1 to 3, then during week 4, 8, 12, 16, 20, 26, 40, 52 in year 1 of the study, then every 6 months until the end of study.

Study Results

After completion of the study, it appears that eculizumab is an effective treatment for patients with refractory myasthenia gravis. Patients who were in the control group had rapid improvements in both their MG-ADL and QMG scores throughout the entirety of the study. Patients also experienced rapid improvement in all MG-ADL and QMG domains, which include ocular, respiratory, bulbar, and limb/gross motor muscle groups, thus, vastly improving these patients’ quality of life. This further proves that inhibition of the C5 complement protein is an effective treatment strategy in refractory myasthenia gravis.

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