RESUMO
BACKGROUND: As treatment goals in Crohn's disease (CD) evolve, targets now include clinical remission (CR), mucosal healing (MH) and biological remission [C-reactive protein normalisation (CRPnorm )]. AIMS: To evaluate the association of baseline factors and treatment with the achievement of different composite remission parameters at week 26. METHODS: This post hoc analysis of the SONIC trial evaluated different composite remission measures at week 26 in a subgroup of patients with Crohn's disease activity index (CDAI) scores, CRP, and endoscopic data available at baseline and week 26 (N = 188). Assessed composite remission measures were: CR (CDAI < 150) and MH (absence of any mucosal ulcerations), previously referred to as 'deep remission;' and alternative composite endpoints: CR + CRPnorm (CRP < 0.8 mg/dL); CRPnorm + MH; and CR + CRPnorm + MH. RESULTS: Among analysed patients, 136/188 (72.3%) achieved CR and 90/188 (47.9%) achieved MH at week 26. All composite outcomes were significantly greater (Bonferroni significance level, P ≤ 0.016) with combination therapy (i.e. infliximab and azathioprine; 52.3-63.6%) vs. azathioprine monotherapy (12.9-29.0%; p ≤ 0.005 for all comparisons). Composite remission rates including MH were significantly greater with combination therapy (52.3-56.9%) vs. infliximab (25.6-32.3%; P ≤ 0.015 for all comparisons except CRPnorm + MH, P = 0.017) and vs. azathioprine monotherapy (12.9-20.4%; P ≤ 0.002 for all comparisons). Median serum trough infliximab concentrations among patients who achieved MH or CR + MH were greater when compared with those among patients who did not achieve MH (P = 0.018) or CR + MH (P = 0.053). Among the subgroup of patients with early Crohn's disease, MH alone or in combination with composite remission criteria significantly improved clinical outcomes of patients who received combination therapy. CONCLUSIONS: Combination therapy was more effective in achieving various composite remission measures vs. azathioprine or infliximab monotherapy. These data illustrate that 'deep remission' is achievable with combination therapy in a high percentage of patients with early Crohn's disease. ClinicalTrials.gov number: NCT00094458.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Azatioprina/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Imunossupressores/uso terapêutico , Adulto , Anticorpos Monoclonais/administração & dosagem , Azatioprina/administração & dosagem , Proteína C-Reativa/metabolismo , Quimioterapia Combinada , Endoscopia Gastrointestinal , Feminino , Fármacos Gastrointestinais/administração & dosagem , Humanos , Imunossupressores/administração & dosagem , Infliximab , Mucosa Intestinal/metabolismo , Masculino , Gravidade do Paciente , Qualidade de Vida , Indução de RemissãoRESUMO
The ultrathin sections of the developing otolith of mouse fetuses 15.5 days to 20 days after birth were observed with the aid of the electron microscope. The first step of otolith formation is an aggregation of organic clusters observed in the sacculus of the 15.5-day fetus. These organic structures are modified and assume a hexagonal shape in the 17.5-day fetus. The unmineralized stages of the otolith referred to as the preotolith, serve as the template for future development. One day after birth, at either end of the preotolith, minute tube-like structures develop in which needle-shaped crystallites are initiated. Crystallites continue to develop throughout the hexagonal template which gave rise to a structure containing many regularly arranged needle-shaped crystallites. Based on the present observations, the mouse otolith is considered a multi-iso-oriented crystal.