RESUMO
Biologic therapies have greatly advanced the medical care of patients with Crohn's disease (CD); however, up to 50% of patients have no response and up to 80% fail to achieve remission.1-4 One way to investigate this treatment gap in CD is to look at the "net" remission rates in clinical trials defined as the actual percentage of patients enrolled during induction who are in remission at the end of maintenance. Indeed, most of the seminal clinical trials in CD used a "responder" methodology, where only patients who responded during induction were rerandomized to maintenance.
Assuntos
Produtos Biológicos , Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Indução de Remissão , Produtos Biológicos/uso terapêuticoAssuntos
Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Produtos Biológicos/efeitos adversos , Tomada de Decisão Clínica , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Indução de Remissão , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/efeitos adversosRESUMO
Pegylated interferon (peginterferon) alfa-2b plus ribavirin achieves a higher sustained response rate in patients with genotype 1 chronic hepatitis C virus (HCV) than standard combination therapy. This study evaluated HCV kinetics throughout therapy with 2 doses of peginterferon alfa-2b and ribavirin in 55 patients. Twenty-eight patients were randomized to receive a high once-weekly dose of peginterferon alfa-2b (3 microg/kg for 1 week, 1.5 microg/kg for 3 weeks, and 1.0 microg/kg for 44 weeks), and 27 patients were randomized to receive a low dose (0.5 microg/kg) for 48 weeks. Both groups also received 800 mg ribavirin daily. Mean baseline HCV RNA load, measured by reverse-transcription polymerase chain reaction, was similar in both groups (5.32 +/- 0.86 log vs. 5.15 +/- 1.04 log). The 3-microg/kg dose of peginterferon alfa-2b inhibited HCV RNA more significantly than the 0.5-microg/kg dose during the first 48 hours (2.08 +/- 0.93 log vs. 1.09 +/- 0.80 log; P <.001) and both increased at 72 hours (0.54 +/- 0.73 log vs. 0.03 +/- 0.36 log; P = not significant [NS]), but the high dose showed a greater reduction at the end of the week (1.07 +/- 0.99 log vs. 0.72 +/- 0.73 log). Both doses showed a progressive, slower viral decrease throughout therapy; however, HCV RNA became undetectable faster and in more patients with the high dose (22% vs. 7% at week 4, 56% vs. 44% at week 12, 69% vs. 63% at week 24, and 71% vs. 61.5% at the end of therapy). In conclusion, peginterferon alfa-2b/ribavirin produces an initial rapid decline in HCV RNA levels, followed by a slower, progressive decrease, similar to the biphasic kinetic profile of standard combination therapy. Higher doses of peginterferon alfa-2b also accelerate viral clearance.