Refractory MG Presents Difficult Challenge for Patients, Clinicians

People with myasthenia gravis (MG) are more likely to have refractory disease if they are a woman, have early-onset disease, or have severe symptoms, according to a new report.

The report, a case series from a Spanish hospital, was published in Neurología, with the authors noting that the “gravis” modifier in the name “myasthenia gravis” refers to the potentially deadly natural course of the disease. However, they noted that newer treatment options have improved outcomes, allowing most patients to live without symptoms or with minimal symptoms.

Yet, an estimated 10% 20% of patients will have cases that are refractory to treatment.

“Generally, these patients are reported to present higher rates of myasthenic crisis, hospital admissions, and emergency care than patients with nonrefractory MG, with a considerable impact on their quality of life,” the authors said.

Since relatively little has been published regarding this important subgroup, the investigators decided to offer insights from a case series of patients with MG seen at their hospital between 2008 and 2019.

Their hospital saw 84 patients with MG, of whom 11 were deemed to be refractory. The investigators defined “refractory” as those cases in which the patient had not responded following treatment with prednisone and at least 2 immunosuppressants, patients for whom doctors were unable to withdraw treatment without relapse in the last 12 months, or patients who could not tolerate treatment due to severe adverse reactions.

The finding that 11 of 84 patients were refractory puts the hospital’s refractory rate within the range reported in previous literature.

The authors said their refractory MG cohort had a median age of 47 years at diagnosis. Most (64%) presented with early-onset generalized MG, nearly triple the 22% rate seen in the nonrefractory group. There was also a higher percentage of women in the refractory group compared with the overall MG group: 82% vs 38%.

Nine of the patients with refractory MG tested positive for anti–acetylcholine receptor antibodies, and 2 had associated thymoma. None of the patients in the refractory MG group tested positive for anti–muscle-specific kinase antibodies.

The authors said patients with refractory MG tended to have greater disease severity at diagnosis, and they experienced more relapses than other patients.

The authors said their findings are generally similar to previous studies, but they added that it can be difficult to compare studies of these patients since there is not yet an agreed-upon definition of refractory cases.

The investigators said they were able to identify patterns in patients’ responses to treatment.

“[T]hey required a continuous escalation of immunosuppressive therapy, frequently receiving such second-line drugs as rituximab (Rituxan), and presented greater likelihood of admission due to exacerbations requiring treatment with intravenous immunoglobulins,” they wrote.

Still, even with those interventions, most patients with refractory cases continued to experience symptoms that had a significant impact on their daily lives.

“While we did not specifically measure disease impact using quality of life scales, we would expect these patients to present considerable difficulties in social and mood-related domains, in addition to their physical limitations,” they wrote.

They said the development of newer therapies could hold the promise of improving outcomes in this patient subgroup, but they noted that new drugs will also require additional research to determine the best stage at which to administer the therapies.

Reference

Garcia-Garcia J, Díaz-Maroto I, Martínez-Martín A, Pardal-Fernández JM, Segura T. A series of patients with refractory myasthenia gravis. Neurologia (Engl Ed). Published online April 7, 2023. doi:10.1016/j.nrleng.2023.04.001