Long-term oral tacrolimus therapy in refractory to infliximab fistulizing Crohn's disease: a pilot study.
OBJECTIVE
To evaluate efficacy and safety of oral tacrolimus in cases of fistulizing Crohn's disease (FCD), which is refractory to conventional therapy including infliximab.


METHODS
Patients with fistulas, previously and unsuccessfully treated with all conventional therapy (i.e., antibiotics, azathioprine, or 6-mercaptopurine and infliximab), were enrolled in a prospective, uncontrolled, open-label study of long-term treatment with oral tacrolimus (0.05 mg/kg every 12 h). The evaluation of the clinical response was complemented by use of the perianal Crohn's disease activity index (PCDAI) and magnetic resonance imaging-based score (MRS) with determined periodicity.


RESULTS
Ten patients were included in the study (enterocutaneous fistula, 3 patients; perianal fistula, 4 patients; rectovaginal fistula, 3 patients) with 6 to 24 months of follow-up. Five patients were steroid-dependent, and 4 patients needed maintenance treatment with immunosuppressant agents. Four patients (40%) achieved complete clinical responses, which were verified by PCDAI and MRS. Five patients (50%) achieved partial responses (i.e., important decreases in fistula drainage, size, discomfort, and PCDAI/MRS values). Decreases in both the PCDAI and MRS were statistically significant (P < 0.05). All steroid-dependent patients stopped therapy with prednisone, and concomitant immunosuppressive therapy was tapered. The response was maintained, and no new flare-up of the disease was observed. Only mild adverse events were detected (1 patient withdrew from treatment due to headache), and no case of nephrotoxicity or diabetes was detected. One patient had received no benefit from therapy after 6 months.


CONCLUSIONS
Oral tacrolimus could be an effective and safe treatment for patients with FCD, even if there has been no response to infliximab treatment. Randomized studies are needed to compare oral tacrolimus with infliximab in terms of efficacy, safety, and costs.
González-Lama
Yago
Y
Gastroenterology and Hepatology Department, Puerta de Hierro Clinic, Madrid, Spain. ygonzalezlama@telefonica.net
Abreu
Luis
L
Vera
Maria Isabel
MI
Pastrana
Miguel
M
Tabernero
Susana
S
Revilla
Juan
J
Durán
Juan Gómez
JG
Escartin
Pedro
P
D000284:Administration, Oral; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy*; D016154:Digestive System Fistula / Q000188:drug therapy* / Q000209:etiology; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; D000069285:Infliximab; D016559:Tacrolimus