BACKGROUND: We studied the toxicity of cyclosporin (CsA), azathioprine, and mesalamine in 94 patients with inflammatory bowel disease (IBD). METHODS: 63 treatments with CsA (2mg/kg intravenously or 5 mg/kg orally); 57 with azathioprine (2 mg/kg); and 44 with mesalamine (3.2-4.8 gr) were included. After induction, oral CsA was continued for 6 months, azathioprine for a median of 14 months (range 1-201 mos), mesalamine until tolerated. RESULTS: CsA toxicity frequency 25%: withdrawal and colectomy in 3 cases. AZA toxicity rate: 43% with an overall time-to-onset of a median of 6 months (range 1-60 mos); withdrawal and colectomy in 7 cases; 62% of the events were other than leukopenia. Mesalamine toxicity rates: (13.6%) with one colectomy. CONCLUSION: Toxicity-related withdrawal of conventional IBD treatments is significant and leads to colectomy in ulcerative colitis. 50% of the thiopurine toxicities outrange the predicting power of the available pharmacogenomic assays; mesalamine often causes allergic lung dysfunction. Efforts are warranted to optimize this conventional treatment of IBD.
BACKGROUND: We studied the toxicity of cyclosporin (CsA), azathioprine, and mesalamine in 94 patients with inflammatory bowel disease (IBD). METHODS: 63 treatments with CsA (2mg/kg intravenously or 5 mg/kg orally); 57 with azathioprine (2 mg/kg); and 44 with mesalamine (3.2-4.8 gr) were included. After induction, oral CsA was continued for 6 months, azathioprine for a median of 14 months (range 1-201 mos), mesalamine until tolerated. RESULTS:CsAtoxicity frequency 25%: withdrawal and colectomy in 3 cases. AZAtoxicity rate: 43% with an overall time-to-onset of a median of 6 months (range 1-60 mos); withdrawal and colectomy in 7 cases; 62% of the events were other than leukopenia. Mesalaminetoxicity rates: (13.6%) with one colectomy. CONCLUSION:Toxicity-related withdrawal of conventional IBD treatments is significant and leads to colectomy in ulcerative colitis. 50% of the thiopurinetoxicities outrange the predicting power of the available pharmacogenomic assays; mesalamine often causes allergic lung dysfunction. Efforts are warranted to optimize this conventional treatment of IBD.