Features of myositis and myasthenia gravis in patients treated with immune checkpoint inhibitors: a multicentric, retrospective cohort study.
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Plomp Lotta, Chassepot Hortense, Psimaras Dimitri, Maisonobe Thierry, Mensi Eric, Leonard-Louis Sarah, Plu Isabelle, Rozes Antoine, Tubach Florence, Touat Mehdi, Anquetil Celine, Wesner Nadege, Champtiaux Nicolas, Rigolet Aude, Demeret Sophie, Weiss Nicolas, Alyanakian Marie-Alexandra, Le Panse Rozen, Truffault Frédérique, Dragon-Durey Marie-Agnès, Chatenoud Lucienne, Abbar Baptiste, Bretagne Marie-Claire, Procureur Adrien, Similowski Thomas, Morelot-Panzini Capucine, Dres Martin, Ederhy Stephane, Benveniste Olivier, Salem Joe-Elie, Allenbach Yves
Аннотация
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.