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.

Keywords: burden; definition; disability; quality of life; refractory myasthenia gravis; side effects; tolerability; treatment; unmet need.

Figure 1.

Clinical event rates in patients with MG with and without refractory illness. (a) Annual mean (± standard error) per patient number of hospitalizations and ICU visits in patients with refractory or nonrefractory MG (Study 1), and acute exacerbations in patients with refractory MG (Study 2). (b) Unadjusted percentages of patients who experienced myasthenic crises, myasthenic exacerbations, ER visits, and inpatient hospitalizations over a 1-year period. ER, emergency room; ICU, intensive care unit; MG, myasthenia gravis.

Figure 2.

Mean (± standard deviation) MG-QoL15 scores in patients with different degrees of severity of myasthenia gravis. Higher scores on the QMG instrument indicate greater disease severity; higher scores on the MG-QoL15 indicate worse health-related quality of life. MG-QoL15, 15-item myasthenia gravis quality of life questionnaire; QMG, quantitative myasthenia gravis.