Tacrolimus (FK506) is safe and effective in patients with refractory extraintestinal manifestations of inflammatory bowel disease

Aims: Between five to twenty percent of inflammatory bowel disease patients develop extraintestinal disease manifestations (EIM), which do not always respond to conventional medical or topical therapy. Tacrolimus, a macrolide immunosuppressant inhibiting T-cell activation, is currently approved for the prophylaxis of organ rejection in patients receiving allogeneic liver or kidney transplants. We have recently published the successful use of oral low dose tacrolimus in refractory inflammatory bowel disease (IBD). Here we report our experience in managing refractory EIM in patients with IBD.

Methods: In this retrospective, observational single center study the charts of 29 (16 female, 13 male) adult (mean age: 41.6±11.6 SD years) IBD patients with steroid-dependent (n=15) or steroid-refractory (n=14) inflammatory bowel disease (Crohn's disease, n=7; ulcerative colitis, n=10; pouchitis, n=2) and extraintestinal disease manifestations (reactive arthritis n=14, sclerosing cholangitis=5, pyoderma gangrenosum n=7, erythema nodosum n=1, autoimmune hemolytic anemia n=1, autoimmune hepatitis n=1) were reviewed. Tacrolimus (0.1mg/kg body weight per day) was administered orally in all patients, aiming for serum trough levels of 4–8 ng/mL. No PCP prophylaxis was administered. Mean treatment duration was 33±7.6 SD months (range, 2.8–164.4 months). Patients were followed-up for a mean of 46±7.3 SD months (range, 12–164.4 months). Response was evaluated using a disease activity score (M-CAI), laboratory data, and/or repeated skin inspection plus photo documentation.

Results: 21 patients (72.4%) experienced a clinical and laboratory response, usually between 3 and 5 days. Tacrolimus was particularly effective in dermatologic, hematologic and hepatic EIM. Mean M-CAI values dropped from 12.2 at initiation to 2.5 at 36 months follow-up. Side-effects included a temporary rise of creatinine (n=2, 6.9%), hyperkalemia (n=1, 3.45%), and opportunistic infections (n=1 3.45%).

Conclusion: Oral low dose tacrolimus appears to be safe and effective in refractory EIM of inflammatory bowel disease.