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Rheumatology (Oxford) ; 59(5): 1041-1050, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32344435

RESUMO

OBJECTIVE: To assess: (i) the prevalence, and clinical and imaging characteristics of immune checkpoint inhibitor (ICI)-induced musculoskeletal immune-related adverse events (ir-AEs) in a prospective manner and (ii) whether serum levels of cytokines associated with the Th1/Th2/Th17 response are differentially expressed in patients with and without musculoskeletal Ir-AEs. METHODS: All patients treated with ICI who developed musculoskeletal manifestations were referred to the Rheumatology Department, and an MRI of the involved area(s) was performed. RESULTS: During the study period, a total of 130 patients were treated with ICIs. Of these, 10 (7.7%) developed ICI-induced Ir-AEs. The median time from ICI treatment since development of symptoms was 2.5 months. Three different patterns of musculoskeletal manifestations were found: (i) prominent joint involvement (n = 3); (ii) prominent 'periarticular' involvement (n = 4). These patients had diffuse swelling of the hands, feet or knees. MRI depicted mild synovitis with more prominent myositis and/or fasciitis in the surrounding tissues in all cases; (iii) myofasciitis (n = 3). Clinically, these patients presented with pain in the knee(s)/thigh(s), whereas MRI depicted myofasciitis of the surrounding muscles. Patients with musculoskeletal ir-AEs had significantly higher oncologic response rates compared with patients not exhibiting musculoskeletal ir-AEs (50% vs 12.5%, respectively, P = 0.0016). Cytokine levels associated with a Th1/Th2/Th17 response were similar between patients with and without musculoskeletal ir-AEs. Overall, symptoms were mild/moderate and responded well to treatment, with no need for ICI discontinuation. CONCLUSION: In our cohort, ICI-induced musculoskeletal manifestations developed in 7.7% of patients. Imaging evidence of myofasciitis was found in most patients, indicating that the muscle/fascia is more frequently involved than the synovium.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Fatores Imunológicos/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Doenças Musculoesqueléticas/induzido quimicamente , Doenças Reumáticas/induzido quimicamente , Antineoplásicos Imunológicos/administração & dosagem , Estudos de Coortes , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Esquema de Medicação , Fasciite/induzido quimicamente , Fasciite/diagnóstico por imagem , Fasciite/epidemiologia , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Incidência , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/diagnóstico por imagem , Doenças Musculoesqueléticas/epidemiologia , Miosite/induzido quimicamente , Miosite/diagnóstico por imagem , Miosite/epidemiologia , Estudos Prospectivos , Doenças Reumáticas/diagnóstico por imagem , Doenças Reumáticas/epidemiologia , Índice de Gravidade de Doença
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