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. DESIGN AND SETTING: This was a prospective, uncontrolled, open-label observational study performed at a university tertiary care center. PATIENTS: 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. INTERVENTION: Adalimumab was injected locally along the fistula tract and around the internal orifice every 2 weeks. MAIN OUTCOME MEASURES: 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. LIMITATIONS: 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.