Myasthenia gravis (MG) is a chronic disease characterised by varying degrees of weakness of the muscles that control the limbs, face, mouth, throat and chest. MG typically affects women aged less than 40 years and older men (over 60 years). MG is a rare disease, affecting only 30.5 in 100,000 people in the United Kingdom (UK) in 2013. While modern treatments allow patients to lead productive lives, 10%-15% of patients are unresponsive to standard treatment. Many of these patients experience worsened symptoms all of the time, which significantly reduces their ability to engage in simple daily activities such as talking, chewing, swallowing, walking, driving and even breathing normally. These patients are additionally at increased risk of lung failure (myasthenic crisis). For these patients, there is an unmet need for a new therapy that can safely and effectively control the disease. The aims of this study are therefore to identify and describe non-responsive (refractory) patients and to assess their burden of illness.
MG is an autoimmune disorder of the neuromuscular junction caused by autoantibodies at the nicotinic acetylcholine (AChR) or muscle-specific tyrosine kinase (MuSK) receptors. Initially typical patients present with extraocular muscle weakness (ptosis or diplopia), and subsequently develop limb, bulbar, and/or muscle weakness (Generalised MG). Standard first-line treatment for MG involves acetylcholinesterase inhibitors or thymectomy followed by prednisolone, a corticosteroid. Patients whose symptoms do not sufficiently respond to these therapies are administered immunosuppressants (ISTs) and/or intravenous immunoglobulins (IVIg). Approximately 10-15% of patients cannot tolerate and/or do not respond to an escalating regimen involving ISTs/IVIg and continue to demonstrate symptoms; these patients are known as 'refractory', These patients experience severe and debilitating symptoms, including: slurred speech, difficulty chewing and swallowing, impaired vision, limb and respiratory weakness and even respiratory failure (myasthenic crises). Using real-world data from the UK Clinical Practice Research Datalink (CPRD), this study aims to identify patients with refractory generalised MG, and to assess their burden of illness, in clinical and humanistic terms, and their resource utilisation relative to patients with non-refractory MG and age- and gender-matched individuals without MG using CPRD and a patient questionnaire. This will help quantify the magnitude of unmet need for a therapy that can help this difficult-to-treat population.
Myasthenic Crisis
- Exacerbation
- Treatment use
- Resource Utilisation - GP visits/nurse visits/home or telephone visit, hospital admissions, ER visits, hospital length of stay
Delphine Saragoussi - Chief Investigator - Evidera, Inc
Brian Sanderson - Collaborator - PPD - UK
Gilbert L'Italien - Collaborator - Alexion Pharma UK Ltd ( UK )
Jacob Saiju - Collaborator - University Hospitals Birmingham
Jennifer Hynson - Collaborator - PPD North America
Sharon MacLachlan - Collaborator - Evidera, Inc
Sophie Graham - Collaborator - Evidera, Inc
Alex Exuzides - Chief Investigator - Evidera, Inc
Alex Exuzides - Corresponding Applicant - Evidera, Inc
HES Accident and Emergency;HES Accident and Emergency;HES Admitted Patient Care;HES Admitted Patient Care;HES Outpatient;HES Outpatient;ONS Death Registration Data;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Patient Level Index of Multiple Deprivation