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1.
Rheumatology (Oxford) ; 58(7): 1214-1220, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690633

RESUMO

OBJECTIVE: Post-hoc analyses of the Rituximab in Myositis trial indicate that specific autoantibodies profiles may influence treatment response. We compared the efficacy and safety of rituximab in anti-synthetase antibody (ARS-ab) positive and negative patients. METHODS: Adult idiopathic inflammatory myopathy (IIM) subjects in the Swedish Rheumatology Quality Register who received ⩾ 1 cycle of rituximab were enrolled. Efficacy assessment was based on the International Myositis Assessment and Clinical Studies (IMACS) core set measures and the 2016 ACR/EULAR definition of improvement for PM and DM. Safety assessment included drug-related adverse event and death during study period. Comparisons were done within and between the ARS-ab defined groups before and after first and last cycles. Associations between selected clinical features and improvement after one rituximab cycle were assessed using logistic regression. RESULTS: Sixty-five subjects were included and 43 had a follow-up visit within 5-10 months. Seventy-eight percent of ARS-ab positive subjects had moderate/major ACR/EULAR improvement after one cycle compared with 50% in the ARS-ab negative group. After several cycles, 79% of the ARS-ab positive and 67% of the ARS-ab negative patients achieved moderate/major improvement. A significant glucocorticoid-sparing effect was only observed in the ARS-ab positive group (P = 0.001). The most frequent adverse events were infections. One ARS-ab positive and two ARS-ab negative patients died during follow-up period. CONCLUSION: Irrespectively of their autoantibody status, a majority of subjects treated with several rituximab cycles had moderate/major improvement. In addition, ARS-ab positive subjects experienced a significant glucocorticoid-sparing effect.


Assuntos
Antirreumáticos/uso terapêutico , Autoanticorpos/sangue , Ligases/imunologia , Miosite/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Idoso , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Biomarcadores/sangue , Esquema de Medicação , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/imunologia , Sistema de Registros , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Índice de Gravidade de Doença , Resultado do Tratamento
2.
J Clin Rheumatol ; 22(2): 51-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26906295

RESUMO

BACKGROUND: Factors associated with survival in patients with idiopathic inflammatory myopathies are heterogeneous. OBJECTIVE: This study aimed to describe clinical and prognostic factors associated with survival in Mexican patients with idiopathic inflammatory myopathies. METHODS: Patients with dermatomyositis (DM) and polymyositis (PM) seen at a tertiary care center from 1985 to 2012 were included. Demographic and clinical characteristics, comorbidities, treatment, and the time to death were recorded. Patients with juvenile DM were excluded. Univariate and multivariate analyses were performed to identify factors associated with mortality. RESULTS: A total of 264 patients with DM and 69 patients with PM were studied. Patients with DM had lower levels of creatine phosphokinase, less cumulative dose of prednisone, higher frequency of dysphagia, and no difference in frequency of interstitial lung disease compared with patients with PM. Patients with DM had lower survival during the first 4 years of disease (80%; 95% confidence interval [CI], 0.74-0.85 vs 89%; 95% CI, 0.78-0.95; P = 0.03 log-rank). Respiratory failure due to pulmonary infection was the main cause of death in patients with DM; miscellaneous causes were responsible for death in patients with PM. Muscular strength (hazard ratio [HR], 0.48; 95% CI, 0.27-0.83; P = 0.01), platelet count (HR, 0.98; 95% CI, 0.98-0.99; P = 0.002), as well as ever use of methotrexate (HR, 0.21; 95% CI, 0.07-0.65; P = 0.007) and azathioprine (HR, 0.21; 95% CI, 0.06-0.68; P = 0.009) were independent factors associated with mortality in patients with DM; in those with PM, only cancer was associated (HR, 8.0; 95% CI, 1.4-43.9; P = 0.01). CONCLUSIONS: Patients with DM had lower survival during the first 4 years of disease than patients with PM. Factors associated with mortality differed in both groups.


Assuntos
Miosite/mortalidade , Adulto , Causas de Morte , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Miosite/complicações , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida
3.
EMBO Mol Med ; 15(10): e17240, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37522383

RESUMO

Idiopathic inflammatory myopathies (IIM) are rare autoimmune systemic diseases characterized by muscle weakness and the presence of muscle-infiltrating T cells. IIM represent a clinical challenge due to heterogeneity of symptoms and variability of response to immunosuppressive treatment. Here, we performed in-depth single-cell sequencing on muscle-infiltrating T cells and peripheral blood memory T cells in six patients with recently diagnosed IIM. We identified tissue resident memory T-cell (TRM ) signatures including the expression of HOBIT, XCL1 and CXCR6 in the muscle biopsies of all patients with IIM. Clonally expanded T-cell clones were mainly found among cytotoxic and TRM implying their role in the disease pathogenesis. Finally, identical expanded T-cell clones persisting at follow-up in the muscle tissue of two patients suggest their involvement in disease chronicity. Our study reveals a muscle tissue resident memory T-cell signature in patients with IIM and a transcriptomic map to identify novel therapeutic targets in IIM.


Assuntos
Doenças Autoimunes , Miosite , Humanos , Linfócitos T , Miosite/diagnóstico , Miosite/terapia , Músculos
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