RESUMO
OBJECTIVE: To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting. METHODS: Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) <2.6, changes in PROMs and radiographic progression. RESULTS: A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP <2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients. CONCLUSION: Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.
Assuntos
Antirreumáticos , Artrite Reumatoide , Azetidinas , Purinas , Pirazóis , Sulfonamidas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Azetidinas/uso terapêutico , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , Medidas de Resultados Relatados pelo Paciente , Purinas/administração & dosagem , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Índice de Gravidade de Doença , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Falha de Tratamento , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/efeitos adversosRESUMO
Pulse therapy with high-dose glucocorticoids (GCs) is widely used as "bridging therapy" for the treatment of patients with active rheumatoid arthritis (RA). Oral pulsed dexamethasone therapy has never been used for this purpose. We determined the clinical efficacy of oral pulsed dexamethasone treatment in patients with early active RA, concomitantly starting with disease-modifying anti-rheumatic drugs (DMARDs). Fourteen early RA patients, glucocorticoid-naive and with active disease for less than 1 year were included. Ten patients were treated with oral pulsed dexamethasone therapy for 4 days in a row. Of this group, four patients received 10 mg dexamethasone/day, three patients 20 mg/day, and three patients 40 mg/day. As controls, four patients were treated with intramuscular methylprednisolone injections. Disease activity (ascertained by disease activity score [DAS]) and biochemical variables were measured at base line, and biweekly thereafter for up to 4 weeks, and monthly thereafter for up to 3 months. A decrease in disease activity, similar in all subgroups, was observed. Nine of 10 patients responded favorably (decrease in DAS of >1.2) 4 weeks after the start of the study. This response was sustained in the months thereafter. One patient did not respond at all, and disease progression during treatment was observed in one patient. No side effects were reported. Only once was a decrease in cortisol level observed; this was at 2 weeks after the start of the study (0.03 micromol/L, reference value 0.18-0.70 micromol/L). Oral pulsed dexamethasone therapy seems to be effective and safe as bridging therapy in early rheumatoid arthritis. The results of the present study justify a long-term controlled trial to compare oral pulsed dexamethasone treatment (10 mg dexamethasone, once weekly for 4 weeks) with the standard GC regimes in the near future.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Administração Oral , Adulto , Idoso , Artrite Reumatoide/patologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de TempoAssuntos
Articulação do Joelho/diagnóstico por imagem , Doenças Linfáticas/diagnóstico por imagem , Octreotida/análogos & derivados , Ácido Pentético/análogos & derivados , Compostos Radiofarmacêuticos , Receptores de Somatostatina/metabolismo , Sarcoidose/diagnóstico por imagem , Adulto , Feminino , Humanos , Radioisótopos de Índio , CintilografiaAssuntos
Dexametasona/uso terapêutico , Desenho de Fármacos , Glucocorticoides/uso terapêutico , Pulsoterapia , Doenças Reumáticas/tratamento farmacológico , Administração Oral , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Glucocorticoides/administração & dosagem , Humanos , Indução de Remissão , Doenças Reumáticas/fisiopatologia , Índice de Gravidade de DoençaRESUMO
We report two case histories of patients with massive rectal blood loss. Endoscopic and radiological investigations could not identify the source of bleeding at admission. Initially, both patients recovered without surgical intervention, receiving a large number of blood transfusions only. Extensive subsequent radiological analysis showed that the bleeding was due to a pathological part of the proximal jejunum in one case and of the colon transversum in the other. Although immediate surgical intervention was not needed at presentation, both patients underwent resection of a part of the bowel some time thereafter. Surgery was performed after hemodynamic stabilization in the first case. However, in the second case, emergency surgical intervention was needed due to persistent bleeding 4 days after admission. Both patients are still doing well half a year after this massive gastrointestinal (GI) hemorrhage. Aside from a small area of chronic inflammation and fibrosis of the jejunum in one patient, histopathological evaluation of the surgical resection specimens revealed no specific cause for these massive gastrointestinal bleedings. We discuss the general approach of gastrointestinal hemorrhage and the several (dis)advantages of the various imaging techniques and the order in which they should be used.