RESUMO
BACKGROUND: In previous trials, budesonide 6 mg/day was able to prolong the time to relapse in patients with quiescent Crohn's disease and budesonide 9 mg/day was effective in active disease with limited side effects. The aim of this study was to compare the effectiveness of budesonide 9 mg vs 6 mg once daily on the maintenance of remission and occurrence of adverse events. METHODS: Double-blind, randomised trial in patients with Crohn's disease in remission. Patients were randomised to receive 6 mg/day or 9 mg/day of budesonide (Budenofalk) without concomitant treatment for Crohn's disease. Endpoints were the time to relapse and relapse rates after one year. RESULTS: Seventy-six patients were randomised to 6 mg/day and 81 patients to 9 mg/day. Survival analysis showed no differences in the time to relapse. One-year relapse rates were not significantly different (6 mg group 24%; 9 mg group 19%). Any adverse event was reported in 61 and 68% of patients in the 6 mg and 9 mg groups, respectively; none of the 12 serious adverse events were drug related. CONCLUSION: The one-year relapse rates were low and not significantly different between the group of patients treated with budesonide 6 mg vs 9 mg/day. Also, time to relapse and the number of adverse events were similar in both treatment groups.
Assuntos
Budesonida/administração & dosagem , Doença de Crohn/tratamento farmacológico , Relação Dose-Resposta a Droga , Adulto , Idoso , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Budesonida/efeitos adversos , Budesonida/uso terapêutico , Método Duplo-Cego , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Prevenção Secundária , Análise de SobrevidaRESUMO
BACKGROUND AND AIMS: Interleukin-10 is an anti-inflammatory and immunomodulatory cytokine. Interleukin-10 deficient mice are prone to develop chronic colitis. Administration of recombinant human interleukin-10 has been proposed to have a beneficial effect in a subgroup of patients with Crohn's disease. Recently, we found an interleukin-10 Gly15Arg mutation in a family with Crohn's disease which is associated with reduced interleukin-10 secretion by in vitro stimulated monocytes and lymphocytes. We hypothesised that this interleukin-10 mutation plays a role in maintaining the inflammatory process in Crohn's disease in some families. PATIENTS AND METHODS: We evaluated interleukin-10 Gly15Arg in 379 patients with Crohn's disease, and 75 unrelated healthy controls. Also, first degree family members of interleukin-10 Gly15Arg carriers were evaluated. Additionally, mutation carriers and their relatives were evaluated for CARD15 R702W, G908R, and 1007fs. RESULTS: Two patients with Crohn's disease were heterozygous for the interleukin-10 Gly15Arg mutation. No homozygotes were found. The Gly15Arg mutation was not observed in the controls. In first degree family members of the Crohn's disease-affected interleukin-10 Gly15Arg carriers, the mutation was found in Crohn's disease-affected as well as in their apparently healthy individuals. All family members carried one or two CARD15 mutation(s). CONCLUSION: The interleukin-10 Gly15Arg mutation is rare in patients with Crohn's disease, and is not associated with the disease in the Netherlands.
Assuntos
Doença de Crohn/genética , Interleucina-10/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação Puntual , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Arginina/genética , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Glicina/genética , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Proteína Adaptadora de Sinalização NOD2 , Mapeamento por RestriçãoRESUMO
BACKGROUND: Mucosal biotransformation enzymes can modify toxic compounds in the gut. As chemical or oxidative stress may be involved in the aetiology of Crohn's disease, genes encoding for enzymes involved in the prevention of such stress may be candidates for genetic susceptibility to Crohn's disease. AIM: To assess the association of Crohn's disease with genetic polymorphisms in cytochrome P450 1A1, glutathione S-transferases mu-1, pi-1, and theta-1, and epoxide hydrolase. METHODS: chi(2) square analysis was used to compare frequencies of polymorphisms between 151 patients with Crohn's disease and 149 healthy controls. RESULTS: In patients, a genetic polymorphism in exon 3 of the microsomal epoxide hydrolase gene was distributed significantly different compared with controls (chi(2)=23.7; p<0.0001). All other polymorphisms tested were equally distributed between patients and controls. CONCLUSIONS: Microsomal epoxide hydrolase may play a role in the pathophysiology of Crohn's disease. Furthermore, the epoxide hydrolase gene is located on chromosome 1q, close to a region previously linked to Crohn's disease.