An Aggressive Medical Approach for Inflammatory Bowel Disease: Clinical Challenges and Therapeutic Profiles in a Retrospective Hospitalbased Series

Giovanni      C. Actis; Floriano      Rosina; Rinaldo      Pellicano; Mario      Rizzetto

Abstract

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 timeto- 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.

Keywords: Azathioprine, Crohn’s disease, cyclosporin, inflammatory bowel disease, mesalamine, ulcerative colitis, Hypersensitivity, Infection, Neurotox, Gastric intolerance, Neoplasia, Fatality, Hematologic tox