Tacrolimus induces short-term but not long-term clinical response in inflammatory bowel disease.

Background: Tacrolimus is a calcineurin inhibitor commonly used for prophylaxis of rejection in renal and liver transplantation. There are limited but favourable data regarding its possible use in patients with inflammatory bowel disease (IBD).

Aims: To evaluate the efficacy and safety of tacrolimus in patients with IBD in clinical practice.

Methods: We performed a retrospective, multicentre study in 22 centres in Spain. All adult patients who received oral tacrolimus for luminal or perianal IBD were included. Clinical response was assessed by Harvey-Bradshaw index and partial Mayo score after 3 months. Perianal disease was evaluated by fistula drainage assessment.

Results: One hundred and forty-three patients were included (mean age 38 years; 51% male; median disease duration 110 months). In ulcerative colitis (UC) (n = 58), the partial Mayo score decreased after 3 months from median 6 to 3 (P = 0.0001), whereas in Crohn's disease (CD) (n = 85), the Harvey-Bradshaw index decreased after 3 months from median 9 to 7 (P = 0.011). In CD patients, blood tacrolimus concentrations during induction (>10 ng/mL vs <10 ng/mL; odds ratio 0.23, 95% CI 0.05-0.87) and the concomitant use of thiopurines (odds ratio 0.18, 95% CI 0.04-0.81) were associated with lower clinical disease activity at 3 months. Of 62 patients with perianal disease, complete closure was observed in 8% (n = 5) of patients with perianal fistulas, with 34% (n = 21) showing partial response. Treatment was maintained for a median of 6 months (IQR, 2-16). After a median clinical follow-up of 24 months (IQR, 15-57), the rate of treatment-related adverse events was 34%, correlating with blood drug concentrations (P = 0.021). Finally, 120 patients (84%) discontinued tacrolimus, usually due to absence or loss of response. Three patients (2%) were subsequently diagnosed with cancer. The overall rate of surgery was 39%, with a 33% colectomy rate in UC.

Conclusions: Tacrolimus shows a clinical benefit in both CD and UC after 3 months of treatment, but its long-term effectiveness and frequent adverse events remain relevant issues in clinical practice.