Understanding the burden of refractory myasthenia gravis

Abstract

Myasthenia gravis (MG) is an autoantibody-mediated disease that compromises the acetylcholine receptors or associated structures of the postsynaptic membrane of the neuromuscular junction. This leads to impaired neuromuscular transmission and subsequent fluctuating fatigability and weakness of ocular, bulbar, and limb skeletal muscles. Over the past few decades, there have been significant advances in our understanding of the disease pathophysiology and improvements in prognosis due to intensive care medicine and immunomodulation. Despite this, an estimated 10–20% of patients with MG do not achieve an adequate response, are intolerant to conventional treatment, or require chronic treatment with intravenous immunoglobulins or plasma separation procedures. Such patients are regarded as having MG that is ‘refractory’ to treatment and may represent a distinct clinical subgroup. Because the majority of patients with MG have well-controlled disease, the burden of illness in the minority with refractory disease is poorly understood and may be underestimated. However, clinically these patients are liable to experience extreme fatigue, considerable disability owing to uncontrolled symptoms, and frequent myasthenic crises and hospitalizations. Both acute adverse effects and an increased risk of comorbidity from treatment regimens may contribute to reduced quality of life. As yet, little is known concerning the impact of refractory MG on mental health and health-related quality of life. This review aims to highlight the burden of disease and unmet needs in patients with refractory MG.

Frequency and clinical features of treatment-refractory myasthenia gravis

“…However, approximately 10-15% of patients still show a poor response to available standard treatments and consequently continue to suffer from disabling symptoms. They also experience frequent disease exacerbations leading to a reduced quality of life and frequent admissions to hospitals and emergency departments [8][9][10][11]. In addition, the necessary treatment with high-dose immunosuppressive drugs is often associated with side effects, which negatively affects patients' quality of life.…”

Quality of life in refractory generalized myasthenia gravis: A rapid review of the literature

“…There are few therapeutic options for this last subtype of the disease (refractory GMG) becoming an unfulfilled requirement (29). Therapies such as rituximab have shown some benefits in small studies and individual cases of refractory MG, and other therapies are under investigation, such as rozanolixizumab and abatacept (30). Currently, eculizumab is the only alternative with phase III studies approved for these symptoms.…”

Update on immune‐mediated therapies for myasthenia gravis

“…Several surgical techniques are used for thymectomy. While the extended transsternal approach has been the affirmed method for many years, use of minimally invasive techniques including video‐assisted thoracoscopic surgery (VATS) and robotic approaches is increasing 6,26 . A recent meta‐analysis comparing robotic method to VATS or to open thymectomy for MG found that robotic thymectomy was comparable to VATS and was superior to open surgery.…”