Outcome Predictors for Thiopurine Maintenance Therapy in Patients with Crohn’s Disease

Abstract

Little is known about the factors that predict clinical relapse in Crohn's disease patients receiving thiopurine therapy to maintain remission. The objective of this study was, therefore, to investigate these factors. A total of 82 Crohn's disease patients who received their first course of azathioprine or 6-mercaptopurine treatment at Severance Hospital between June 1996 and July 2007 were recruited to the study. During the follow-up period (25.5 ± 16.6 months) 19 patients (23.2%) discontinued the medication because of significant adverse effects. Forty-five patients who continued to receive thiopurines to maintain medically or surgically induced remission were enrolled in the study. After adjusting the maintenance dose, patients in remission were followed at 2-3 month intervals. Relapse was defined as a Crohn's disease activity index ≥ 150. The male-to-female ratio was 1.5:1 and the mean age was 26.3 ± 7.1 years. Cumulative relapse was 18.0% after one year and 49.2% after three years. According to multivariate Cox regression analysis, younger age (<30 years) at thiopurine therapy and increased C-reactive protein level (≥ 0.5 mg/dL) at remission were independent predictors of relapse (hazard ratio 19.751, 95%-confidence interval (CI) 1.996-195.402, P = 0.011 and hazard ratio 9.001, 95% CI 1.583-51.181, P = 0.013, respectively). Younger age (<30 years) and increased C-reactive protein level at remission were independent predictors of relapse in Crohn's disease patients receiving thiopurines to maintain remission. These high-risk groups warrant closer observation and possibly early introduction of biological agents.