RESUMO
There is a significant rate of therapeutic failure in rheumatoid arthritis (RA) patients treated with leflunomide (LEF). This study investigates the utility values of teriflunomide levels (A77 1726) in identifying RA patients who remained with moderate or severe disease activity after the treatment with LEF. In this cross-sectional study, we compared: (a) RA patients who achieved a DAS28-ESR ≤ 3.2, and (b) RA patients who maintained a DAS28-ESR > 3.2 after treatment. ROC curves determined the cut-off of A77 1726 with the better performance to identify patients achieving a DAS28-ESR ≤ 3.2. Of the 115 patients treated with LEF, 69 (60%) remained with moderate/severe disease activity and 46 (40%) achieved low disease activity/remission. Higher A77 1726 levels showed a negative correlation with DAS28-ESR (r = - 0.42, p < 0.001) and other parameters of disease activity. We obtained the following utility values with the cut-off of A77 1726 > 10 µg/mL to identify RA patients who achieved a DAS28-ESR ≤ 3.2: sensitivity of 91.31%; specificity of 73.91%; positive predictive value of 70.00%; and negative predictive value of 92.73%. Serum A77 1726 discriminated between RA patients who remained with moderate/severe disease activity despite the treatment with LEF both as monotherapy and LEF as combo therapy.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Crotonatos/uso terapêutico , Hidroxibutiratos/uso terapêutico , Leflunomida/uso terapêutico , Nitrilas/uso terapêutico , Toluidinas/uso terapêutico , Adulto , Idoso , Antirreumáticos/efeitos adversos , Antirreumáticos/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Estudos Transversais , Crotonatos/efeitos adversos , Crotonatos/sangue , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Hidroxibutiratos/efeitos adversos , Hidroxibutiratos/sangue , Leflunomida/efeitos adversos , Leflunomida/sangue , Masculino , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Nitrilas/sangue , Valor Preditivo dos Testes , Indução de Remissão , Índice de Gravidade de Doença , Fatores de Tempo , Toluidinas/efeitos adversos , Toluidinas/sangue , Resultado do TratamentoRESUMO
RATIONALE: Teriflunomide is an inhibitor of pyrimidine synthesis available as a first-line treatment for relapsing-remitting multiple sclerosis. Drug-induced liver damage is a relevant problem in clinical practice, representing a frequent cause of treatment discontinuation. This case report describes the occurrence of liver injury, with a 33.7-fold increase in the upper limit of normality of the liver enzyme alanine aminotransferase during treatment with teriflunomide 14âmg. PATIENT CONCERN: A 44-year-old woman receiving teriflunomide 14âmg for the treatment of multiple sclerosis presented symptoms suggestive of liver dysfunction 54âdays after starting treatment. The patient had no history of using disease-modifying therapy, neither previous liver disease nor other comorbidities. DIAGNOSTICS: The suggested diagnosis was drug-induced liver injury, classified as hepatocellular. Other possible hepatic and autoimmune etiologies were ruled out. INTERVENTIONS: Replacement of teriflunomide treatment with glatiramer acetate and follow-up of the disease. OUTCOMES: Signs and symptoms regressed after treatment with teriflunomide 14âmg was discontinued, with normalization of liver enzyme activity in â¼5âmonths. The causality assessment of the adverse drug reaction was determined by the Naranjo scaling system, resulting in probable, with a final score of 7. CONCLUSIONS: Teriflunomide-induced liver injury in patients with multiple sclerosis is a serious adverse reaction. The report of this case contributes to updating knowledge about the safety aspects of treatment with teriflunomide and planning of monitoring strategies and patient risk management.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Crotonatos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hidroxibutiratos/efeitos adversos , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla/tratamento farmacológico , Nitrilas/efeitos adversos , Toluidinas/efeitos adversos , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Crotonatos/uso terapêutico , Feminino , Humanos , Hidroxibutiratos/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Nitrilas/uso terapêutico , Toluidinas/uso terapêutico , Resultado do TratamentoRESUMO
Purpose: To determine the efficacy of norbixin-based poly(hydroxybutyrate) (PHB) membranes for Achilles tendon repair. Methods: Thirty rats were submitted to total tenotomy surgery of the right Achilles tendon and divided into two groups (control and membrane; n = 15 each), which were further subdivided into three subgroups (days 7, 14, and 21; n = 5 each). Samples were analyzed histologically. Results: Histological analysis showed a significant reduction in inflammatory infiltrates on days 7, 14 (p 0.0001 for both), and 21 (p = 0.0004) in the membrane group compared to that in the control group. There was also a significant decrease in the number of fibroblasts in the control group on days 7, 14 (p 0.0001), and 21 (p = 0.0032). Further, an increase in type I collagen deposition was observed in the membrane group compared to that in the control group on days 7 (p = 0.0133) and 14 (p = 0.0107). Conclusion: Treatment with norbixin-based PHB membranes reduces the inflammatory response, increases fibroblast proliferation, and improves collagen production in the tendon repair region, especially between days 7 and 14.(AU)
Assuntos
Animais , Ratos , Hidroxibutiratos/efeitos adversos , Hidroxibutiratos/análise , Tenotomia/veterinária , Traumatismos dos Tendões/cirurgia , Ratos/lesõesRESUMO
The purpose of this study was to evaluate the tissue response to a 70% polyhydroxybutyrate and 30% hydroxyapatite composite in the form of a bone implant, placed intracortically in the distal metaphyseal of the right femur, and subcutaneous implants in cats. Samples of the composite were implanted subcutaneously in the dorsolumbar region and the distal metaphyseal region of the right femur of the animals. The study used 12 neutered adult mixed breed cats, weighing an average of 3.5kg. The cats were randomly divided into three groups: GI, GII and GIII, according to the length of the assessment period. The assessments of their subcutaneous and bone tissues were performed at 15, 30 and 45 days and at 30, 60 and 90 days, respectively. The subcutaneous and bone reactions to the composites were characterized by granulomatous inflammation with a predominance of macrophages and giant cells. The results showed that the composites triggered a chronic local inflammatory response, despite their clinical acceptance.