Myasthenia gravis (MG) is a neuromuscular disease with symptoms of muscular weakness and fatigability and is caused by a problem with the signals sent between the nerves and the muscles. It most commonly affects the muscles that control the eyes and eyelids, facial expressions, chewing, swallowing and speaking. But it can affect most parts of the body. In MG, the immune system damages the communication system between the nerves and muscles, making the muscles weak and easily tired. It's not clear why this happens, but it's been linked to issues with the thymus gland (a gland in the chest that's part of the immune system).
Every case of MG is unique and when choosing a treatment, physicians take many factors into consideration such as disease subtype, severity and other medical conditions.
Treatments generally work well, and myasthenia doesn’t necessarily get worse over time but at present it isn’t curable. Disease-specific treatment generally consists of the combined use of treatment targeting symptoms (Acetylcholine esterase inhibitors) and treatment that supress the immune system such as, steroids, non-steroid immunosuppressant and removal of thymus gland. In addition, immunoglobulin and plasma exchange are widely used to treat episodes of worsening, and sometimes as main therapy in patients who do not respond well to other treatments. Recently, new therapy options have emerged for these unresponsive patients, such as biological drugs eculizumab and rituximab, but their effectiveness and long-term safety are still under investigation. Thus, there are still MG patients who would benefit from better treatment options.
To understand the health care burden due to MG in children and adults, this retrospective cohort study aims to assess epidemiology, treatment patterns for the disease, as well as healthcare resource use (HCRU) in an outpatient and inpatient setting in the UK from 2010 to 2019. Study population will include children and adults with at least one diagnosis of MG in either the CPRD or HES during study period. Epidemiology of MG will be assessed in terms of incidence and prevalence in selected years, and treatment patterns during follow-up will be described among incident patients. Clinical burden of disease in incident patients will be expressed as incidence and event rates of MG clinical events (exacerbations, Myasthenic crisis, specific treatments). Linkage to ONS database will be used to assess time and cause of death. Co-morbidities and health economic burden of the disease in terms of healthcare resource utilization in the inpatient and outpatient settings will be reported as incidence and event rates in MG and randomly sampled matched non-MG cohort, and for this objective groups will be compared using conditional logistic regression model to obtain estimate after adjustment for baseline characteristics.
The study will report results separately for adults (≥18 years of age) and children (when feasible).
The following outcomes will be measured in the study:
1. Age, sex, weight and body mass index (BMI) at baseline.
2. Incidence and Prevalence
3. MG-related and All-cause mortality
4. Co-morbidities: autoimmune thyroiditis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, ankylosis spondylitis, psoriasis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, anxiety, depression, dyslipidaemia, obesity, osteoporosis, type 2 diabetes, hypertension and cardiac arrythmias, infections, systemic infection, infections requiring hospitalizations, Charlson co-morbidity index
5. Myasthenia exacerbation and Myasthenia crisis (MC)
6. Treatment patterns with current standard of care therapies (defined in details under Subtitle 17 in the protocol): Acetylcholinesterase inhibitors, steroids, non-steroid immunosuppresants and biologics
7. Health care resource use: Visits to GPs and other healthcare professionals in primary care, GP phone calls, visits to neurologist, visits to any other specialist, outpatient visits (all cause and MG related), day-patient hospitalization (all cause and MG related), ER visits (all-cause and MG-related), admission to hospitals with overnight stay (all cause and MG-related) and length of stay, admission to intensive care unit (all cause and MG-related) and length of stay
8. Ig / PLEX treatment episode overall and during treatment segments
9. Use of corticosteroids overall and during treatment segments: period / episode of steroid use, high dose steroids use, average dose among patients, up-titration, down-titration and discontinuation, episodes of short and long-term use
ALI ABBASI - Chief Investigator - UCB Pharma Ltd
Chao Lu - Corresponding Applicant - UCB BioSciences, Inc.
Nada Boudiaf - Collaborator - UCB BioSciences, Inc.
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data