궤양성 대장염에서 면역억제제 치료

Abstract

Most of patients with ulcerative colitis have intermittent chronic disease demonstrating recurrent flare-ups of bloody diarrhea and symptom-free periods. Sulfasalazine and mesalazine are the first-line medical therapy in patients with mild to moderate activity, as both of them are effective in inducing and maintenance of remission. However, significant proportion of patients needs stronger drugs such as corticosteroids. As corticosteroids are ineffective for the prevention of relapse and associated with frequents side-effects, immunosuppressors, 6-mercaptopurine (6-MP) and its prodrug azathioprine, have been used in selected patients. After absorption azatioprine is rapidly converted to 6-MP non-enzymatically and 6-MP is either inactivated by thiopurine methyltransferase (TPMT) to 6-methylmercaptopurine or by xanthine oxidase to 6-thiouric acid, or it is activated via a multistep enzymatic pathway to the putative active metabolites, 6-thioguanine nucleotides (6-TGN). Clinical responsiveness and side effects are associated with TPMT genotype and phenotype, because the enzymatic activity of TPMT is genetically determined. Until now, significant proportion of patients with proper indication are not receiving immunosuppressors because of safety concern and delayed onset of action. Recently, however, gastroenterologists`` acceptance for immunomodulators is increasing based on favorable results regarding efficacy and safety. The recent application of the study of variability in drug response due to genetic factors, termed pharmacogenetics, has provided a chance for tailored dosing in the individual patients.