Double Trouble: A Retrospective Chart Review of Patients with Immune-Related Myositis and Myasthenia Gravis

Objectives 1. Describe the clinical characteristics of patients presenting with an overlap of immune-related myositis and myasthenia gravis (MG) secondary to immune checkpoint inhibitors (ICIs). 2. Evaluate the management strategies utilized to care for these patients. 3. Identify clinical and treatment-related factors associated with patient outcomes. Methods Clinical data was abstracted from medical records, including demographics, oncologic history, pre-existing autoimmune conditions, manifestations of disease, laboratory findings, treatment, and outcomes. Results 18 patients were identified with overlapping myositis and MG. 50% of MG diagnoses were supported by positive electromyography (EMG) or MRI, and 50% were diagnosed clinically by ocular or bulbar symptoms, and/or fatigable muscle weakness. Myositis was diagnosed by CK elevation, MRI or EMG, and physical findings of sustained proximal muscle weakness. All patients received initial high-dose glucocorticoids, with improvement in 12 of 18 patients. In addition to glucocorticoids, 7 received intravenous immunoglobulins, 1 plasma exchange, 8 acetylcholinesterase inhibitor therapy (pyridostigmine), and 3 disease-modifying antirheumatic drug (DMARD) therapy. DMARD therapies included mycophenolate (symptom improvement in 2 of 3 patients), infliximab (improvement in 1 of 3 patients), and rituximab (deterioration in 1 patient). 7 patients received pyridostigmine, of which 6 had symptom improvement. None required ventilatory support. 3 of 18 patients died from MG/myositis syndrome. Mortality was associated with Grade 4 symptom severity, bulbar involvement, and profound muscle weakness. The presence of MG− or myositis associated antibodies did not predict mortality. Conclusion This multi-center study characterizes a spectrum of clinical presentations among patients with overlapping immune-related myositis and MG. Mortality was associated with Grade 4 symptom manifestations, bulbar symptoms, and need for ventilatory support, highlighting the critical role of early recognition and aggressive management in severe cases.[1] All patients received high-dose glucocorticoids, with some receiving additional immunosuppressive therapies and supportive care. Addition of acetylcholinesterase inhibitor therapy improved overlap symptoms more than DMARD therapy alone. Among those with EMG-confirmed MG, the majority improved with pyridostigmine, further suggesting true neuromuscular junction pathology and arguing against the interpretation that MG diagnoses merely represent severe myositis, which reinforces the concept of distinct overlap syndrome rather than a single disease spectrum. As in previous studies, clinical outcomes were influenced by disease severity and organ involvement rather than serologic markers, as antibody positivity did not correlate with mortality.[2] These findings support the need for multidisciplinary care, early diagnostic evaluation, and individualized treatment strategies to optimize outcomes in patients with overlap syndromes. References [1.] Haugh A. Expert Opin Drug Saf 2020;19:479-88. [2.] Alghabban A. JTO Clin Res Resp 2024;6:100772.