Immune checkpoint inhibitor-related myositis: from pathophysiology to treatment

Abstract

With rapid advances in immuno-oncology, immune checkpoint inhibitors (ICIs) are increasingly used for a broad array of malignancies. This has led to a novel spectrum of adverse effects including ICI-related myositis, a potentially life-threatening neuromuscular complication that must be diagnosed and treated promptly. Significant gaps exist in the current understanding of ICI-related myositis due to the rarity of the condition and the lack of evidence-based guidelines, prompting the need to synthesize the most relevant and recent published works in the field. This review provides a broad overview of ICI-related myositis with an emphasis on pathophysiology, epidemiology, clinical features, workup, management and future directions.

Rare Immune-Related Adverse Events (irAEs): Approach to Diagnosis and Management

“…Electromyography (EMG) revealed a classical myopathic pattern in the majority of patients, and muscle MRI consistently demonstrated muscle oedema. Muscle biopsies often confirmed necrotising and inflammatory changes [ 25 , 36 ]. Management includes corticosteroids as well as consideration of concurrent intravenous immunoglobulin (IVIg), or plasmapheresis [ 25 , 36 ].…”

“…Muscle biopsies often confirmed necrotising and inflammatory changes [ 25 , 36 ]. Management includes corticosteroids as well as consideration of concurrent intravenous immunoglobulin (IVIg), or plasmapheresis [ 25 , 36 ]. Clinical symptoms and CK can be used to track response to treatment [ 36 ].…”

“…Management includes corticosteroids as well as consideration of concurrent intravenous immunoglobulin (IVIg), or plasmapheresis [ 25 , 36 ]. Clinical symptoms and CK can be used to track response to treatment [ 36 ]. Although most patients respond to treatment, mortality was still reported at 17%, with most patients dying due to respiratory failure or sudden cardiac events [ 25 ].…”

“…Ocular myositis is a rare subtype of myositis syndrome in which there is isolated involvement of extraocular muscles. There is significant clinical overlap with ocular myasthenic syndromes (discussed below), with symptoms including diplopia, ptosis and complex ophthalmoplegias, and as such, diagnosis can be challenging [ 36 ]. Pain on eye movements, absence of fatiguability and a myopathic EMG pattern are important differentiators between the conditions.…”

“…Pain on eye movements, absence of fatiguability and a myopathic EMG pattern are important differentiators between the conditions. Presence or absence of antibodies, either myositis-specific or acetylcholine-receptor (AChR) antibodies, are less reliable in differentiating these conditions, as both may be seronegative, or display overlapping syndromes [ 36 ]. Management is similar to other myositis syndromes (discussed above).…”