Features of myositis and myasthenia gravis in patients treated with immune checkpoint inhibitors: a multicentric, retrospective cohort study
Lotta Plomp, Hortense Chassepot, Dimitri Psimaras, Thierry Maisonobe, S. Mensi, Sarah Léonard-Louis, Isabelle Plu, Antoine Rozes, Florence Tubach, Mehdi Touat, C. Anquetil, N. Wesner, Nicolas Champtiaux, Aude Rigolet, Sophie Demeret, Nicolas Weiss, Marie‐Alexandra Alyanakian, Rozen Le Panse, Frédérique Truffault, Marie‐Agnès Dragon‐Durey, Lucienne Chatenoud, Baptiste Abbar, Marie-Claire Bretagne, Adrien Procureur, Thomas Similowski, Capucine Morélot-Panzini, Martin Dres, Stéphane Éderhy, Olivier Benvéniste, Joe‐Elie Salem, Yves Allenbach
Abstract
Background: Immune checkpoint inhibitors (ICIs) may induce overlapping myositis/myasthenia gravis (MG) features, sparking current debate about pathophysiology and management of this emerging disease entity. We aimed to clarify whether ICI-induced (ir-) myositis and ir-MG represent distinct diseases or exist concurrently. Methods: We performed a retrospective multicenter cohort study. Using the Paris University Hospitals database (n = 2,910,417), we screened all patients with International Classification of Diseases codes or free text related to myositis/MG signs and ICI (n = 620). 'Ir-MG signs' were defined by fatigability, repetitive nerve stimulation (RNS) decrement, and/or acetylcholine receptor antibodies (AChR Abs). Findings: Ir-MG signs were never observed in the absence of ir-myositis (pathological diagnosis (n = 12/14) or CK levels >8000 U/L (n = 2/14)). Among ir-myositis patients, fatigability (2%; n = 1/62) and RNS decrement (2%; n = 1/41) were demonstrated only in one patient with pre-existing MG. AChR Abs testing yielded positive results in 26% of ir-myositis patients (n = 14/53). We revealed that test results were already positive prior to ICI therapy (n = 8/9). Clinically, ir-myositis frequently presented with "MG-like" oculomotor disease (50%; n = 31/62), bulbar dysfunction affecting speech (29%; n = 18/62) and swallowing (42%; n = 26/62), and respiratory disorders (53%; n = 33/62). Extraocular and diaphragm muscles necropsies disclosed intense muscle inflammation (100%; n = 5/5). Interpretation: In our extensive database, we found no evidence of isolated ir-MG, nor of clear neuromuscular junction dysfunction in ir-myositis. These findings suggest that patients with ir-MG suspicion frequently have ir-myositis and ir-MG might be rare. "MG-like" symptoms may stem from ir-myositis-specific predilection for oculo-bulbo-respiratory musculature. Indeed, we revealed florid inflammatory infiltration of the oculomotor and respiratory muscles. Additional studies are needed to confirm these results and to elucidate the role of pre-existing AChR Abs in ir-myositis. Funding: None.