Therapy resistant ulcerative colitis associated with high MDR1 function

Background: Current drugs to treat inflammatory bowel disease (IBD) incl. corticosteroids, azathioprine, cyclosporine are all substrates of ABC-MDR transporters. Testing MDR-transporter function to establish personalized treatment strategies is an increasingly accepted issue by various methods including DNA chip arrays and Flow Cytometry. In addition, it is uncertain, whether or not peripheral blood mononuclear cells could be used for screening purposes.

Our patient: a 70 years old female patient was referred to our unit with therapy resistant ulcerative colitis (UC) involving the sigmoid colon and the rectum. She had no relevant past medical or surgical history apart from UC diagnosed 25 years ago with intermittent flare-ups and remissions, multiple boosts of corticosteroids and ongoing ASA therapy. After failure of boost steroids to keep her on sustained remission and considering her age, azathioprine 100mg was introduced along with low-dose methylprednisolone. Both clinical symptoms and the endoscopic appearance of the gut mucosa showed sustained inflammatory activity confirmed by histology (UCAI: 9). Functional MDR tests were performed from the gut mucosa and peripheral blood (MDQ test Solvo Biotechnology) showing highly increased MDR1 protein function of mononuclear cells of the gut mucosa and peripheral blood. Increasing the level of azathioprine resulted in slight improvement in the clinical symptoms, with partial endoscopic remission.

Conclusion: Controlled clinical studies should address the role of MDR-transporters in therapy-resistant IBD. It is of debate, whether or not transporters, once expressed, can be saturated by increasing the dose of drug therapy.