Effectiveness and safety of local adalimumab injection in patients with fistulizing perianal Crohn's disease:  a pilot study.
BACKGROUND
Various blockers of tumor necrosis factor-α are available for treatment of Crohn's disease. Randomized controlled trials have demonstrated the effects of systemic therapy with adalimumab, a fully humanized monoclonal antibody against tumor necrosis factor-α.


OBJECTIVE
The aim of this study was to investigate the effectiveness and safety of local injection of adalimumab along the fistula in the treatment of perianal Crohn's disease.


METHODS
This was a prospective, uncontrolled, open-label observational study performed at a university tertiary care center.


METHODS
A total of 12 outpatients (9 women, 3 men) treated for fistulizing perianal Crohn's disease between 2009 and 2010 were enrolled. The mean age was 43.5 (range, 27-59) years. The fistula was classified as anovaginal in 3 patients, transsphincteric in 7 patients (low in 2, high in 5), and complex (multiple tracts) in 2 patients. Pikarsky's Perianal Crohn's Disease Activity Index was used to evaluate severity of the perianal disease.


METHODS
Adalimumab was injected locally along the fistula tract and around the internal orifice every 2 weeks.


METHODS
The primary end point of the study was the proportion of patients in whom complete or improved healing of fistulas was observed at follow-up, with improvement based on the number of daily changes of sanitary pads.


RESULTS
The median number of injections per patient was 7 (range, 4-16). The mean length of follow-up was 17.5 (range, 5-30) months; 75% of patients (9 of 12) reached complete cessation of fistula drainage, and 3 patients (25%), all with transsphincteric fistula, showed improvement. Comparison of overall follow-up scores on the Perianal Crohn's Disease Activity Index with baseline showed significant improvement (p = 0.002). No adverse side effects were noted.


CONCLUSIONS
The study was limited by its small sample size and by the absence of a control group.


CONCLUSIONS
This pilot study suggests that a high local concentration of adalimumab favors prompt and definitive healing of the fistulous tract in patients with perianal Crohn's disease. Future randomized trials with well-defined selection criteria are needed to determine the relative risks and benefits of available anti-TNF-α blockers (chimeric vs fully humanized) and the optimal mode of administration (systemic use vs local injection) in the treatment of fistulizing perianal Crohn's disease.
Department of Clinical Physiopathology, Surgical Unit, University of Florence Medical School, Florence, Italy. fmed@libero.it
Francesco
F
Tonelli
Francesco
F
Giudici
Corrado Rosario
CR
Asteria
D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000627:therapeutic use; D003424:Crohn Disease / Q000150:complications*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012003:Rectal Fistula / Q000188:drug therapy* / Q000209:etiology; D012006:Rectovaginal Fistula / Q000188:drug therapy / Q000209:etiology; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D000068879:Adalimumab