TY - JOUR
T1 - Features of myositis and myasthenia gravis in patients treated with immune checkpoint inhibitors
T2 - a multicentric, retrospective cohort study
AU - Plomp, Lotta
AU - Chassepot, Hortense
AU - Psimaras, Dimitri
AU - Maisonobe, Thierry
AU - Mensi, Eric
AU - Leonard-Louis, Sarah
AU - Plu, Isabelle
AU - Rozes, Antoine
AU - Tubach, Florence
AU - Touat, Mehdi
AU - Anquetil, Celine
AU - Wesner, Nadege
AU - Champtiaux, Nicolas
AU - Rigolet, Aude
AU - Demeret, Sophie
AU - Weiss, Nicolas
AU - Alyanakian, Marie Alexandra
AU - Le Panse, Rozen
AU - Truffault, Frédérique
AU - Dragon-Durey, Marie Agnès
AU - Chatenoud, Lucienne
AU - Abbar, Baptiste
AU - Bretagne, Marie Claire
AU - Procureur, Adrien
AU - Similowski, Thomas
AU - Morelot-Panzini, Capucine
AU - Dres, Martin
AU - Ederhy, Stephane
AU - Benveniste, Olivier
AU - Salem, Joe Elie
AU - Allenbach, Yves
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/3/1
Y1 - 2025/3/1
N2 - 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.
AB - 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.
KW - Acetylcholine receptor antibodies
KW - Autoimmunity
KW - Biomarker
KW - Immune checkpoint inhibitor
KW - Immune checkpoint inhibitor-induced myasthenia gravis
KW - Immune checkpoint inhibitor-induced myositis
KW - Immune-related adverse event
KW - Immunotherapy
KW - Myasthenia gravis
KW - Myositis
UR - http://www.scopus.com/inward/record.url?scp=85214561591&partnerID=8YFLogxK
U2 - 10.1016/j.lanepe.2024.101192
DO - 10.1016/j.lanepe.2024.101192
M3 - Article
AN - SCOPUS:85214561591
SN - 2666-7762
VL - 50
JO - The Lancet Regional Health - Europe
JF - The Lancet Regional Health - Europe
M1 - 101192
ER -