Article

Effectiveness and Safety of Local Adalimumab Injection in Patients With Fistulizing Perianal Crohn's Disease: A Pilot Study

Department of Clinical Physiopathology, Surgical Unit, University of Florence Medical School, Florence, Italy.
Diseases of the Colon & Rectum (Impact Factor: 3.75). 08/2012; 55(8):870-5. DOI: 10.1097/DCR.0b013e31825af532
Source: PubMed

ABSTRACT

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.
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.
This was a prospective, uncontrolled, open-label observational study performed at a university tertiary care center.
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.
Adalimumab was injected locally along the fistula tract and around the internal orifice every 2 weeks.
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.
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.
The study was limited by its small sample size and by the absence of a control group.
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.

Download full-text

Full-text

Available from: Corrado Rosario Asteria
  • [Show abstract] [Hide abstract]
    ABSTRACT: In 1998, the first TNF-blocker was approved in the USA and a year later in Germany. Treatment with TNF-blocking agents has significantly expanded therapeutic options for patients with chronic inflammatory diseases in rheumatology, dermatology and gastroenterology. However, it is not always possible to achieve a local clinical improvement by systemically administered TNF-blockers. Many approaches to topical therapy with TNF blockers have been published in recent years. The main objective of these off-label applications is the injection of a larger quantity of TNF-blocker in the inflamed tissue than it is achievable with systemic therapy. This summary provides an overview of the variety of topical therapy trials and reports own experiences in patients with Crohn's disease.
    No preview · Article · Feb 2013 · DMW - Deutsche Medizinische Wochenschrift
  • [Show abstract] [Hide abstract]
    ABSTRACT: Crohn’s disease is a chronic inflammatory disease which may involve any segment of the gastrointestinal tract, most frequently the terminal ileum, the large intestine, and the perianal region. The symptoms of perianal Crohn’s disease include skin disorders, hemorrhoids, anal ulcers, anorectal stenosis, perianal abscesses and fistulas, rectovaginal fistulas and carcinoma of the perianal region. The perianal manifestations of Crohn’s disease cause great discomfort to the patient and are among the most difficult aspects to treat. Management of perianal disease requires a combination of different imaging modalities and a close cooperation between gastroenterologists and dedicated surgeons.
    No preview · Article · Mar 2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Unlabelled: Diabetes is now one of the most common un-communicable diseases worldwide. Few studies have dealt specifically with the potential therapeutic effect of TNF-α suppressor to decrease oxidative stress markers in patients with diabetes. The aim of this study was to investigate the potential therapeutic and toxic effect of the direct injection of the anti-TNF-α on oxidative stress mediators, proinflammatory cytokines and vascular risk factors associated with diabetes on diabetic rats. Methods: diabetes was induced by streptozotocin, three weeks after the - induction of diabetes, a polyclonal anti-mouse/rat TNF-α rabbit serum was injected in the treated group and sacrificed after 4 weeks. The expression of TNF-α mRNA was measured by RT-PCR. The levels of TNF-α, VEGF, IL-2, IL- 6, HSP-70, troponin-t, 8-OHdG, ICAM-1 and VCAM-1 were evaluated using ELISA. Myeloperoxiase (MPO) and total peroxides (TPs) levels were estimated by biochemical reactions. Results: the treatment of diabetic rats with the anti-TNF-α caused a significant decrease in the TNF-α mRNA expression, which were paralleled with the decreased levels of TNF-α, IL-6, MOP, HSP-70, ICAM-1, VCAM-1, troponin-t and 8-OHdG in the blood serum. On the contrary, all were highly expressed in the diabetic group that may be the leading reasons for the DNA damage and cell loss. Data revealed that TNF-α, HSP-70, IL-6, MPO and adhesion molecules when expressed in diabetic rats, collectively induce dramatic changes. Conclusion: these new findings suggested that targeting TNF-α could effectively reduce expressions of MCP-1, HSP-70, troponin-t, 8-OHdG and VCAM- 1, along with prominent reduction in MPO and IL-6 levels.
    Full-text · Article · Jul 2013
Show more