Effectiveness and Safety of Local Adalimumab Injection in Patients With Fistulizing Perianal Crohn’s Disease

Tonelli, Francesco; Giudici, Francesco; Asteria, C. R.

doi:10.1097/dcr.0b013e31825af532

Cited by 38 publications

(31 citation statements)

References 27 publications

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“…In a retrospective case series, once again Tonelli et al described the outcomes in 12 patients, in whom 20 mg of ADA diluted to 20 mL of saline was injected into fistula tracts every 2 weeks 50. The median number of injections per patient was 7 (4–16).…”

Section: Conventional Non-biologic Medical Therapy Biologics and Permentioning

confidence: 99%

Modern management of perianal fistulas in Crohn’s disease: future directions

Kotze

Shen

Lightner

et al. 2018

Gut

131

104

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Perianal fistulae in patients with Crohn's disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two decades have seen significant advancements in the management of perianal fistulas in CD, which has evolved into a multidisciplinary approach that includes gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite the introduction of new medical therapies such as antitumour necrosis factor and novel models of care delivery, the best fistula healing rates reported with combined medical and surgical approaches are approximately 50%. More recently, newer biologics, cell-based therapies as well as novel endoscopic and surgical techniques have been introduced raising new hopes that outcomes can be improved upon. In this review, we describe the modern management and the most recent advances in the management of complex perianal fistulising CD, which will likely impact clinical practice. We will explore optimal use of both older and newer biological agents, as well as new data on cell-based therapies. In addition, new techniques in endoscopic and surgical approaches will be discussed.

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Section: Conventional Non-biologic Medical Therapy Biologics and Permentioning

confidence: 99%

Modern management of perianal fistulas in Crohn’s disease: future directions

Kotze

Shen

Lightner

et al. 2018

Gut

131

104

View full text Add to dashboard Cite

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“…For instance, of 12 patients treated with locally injected Adalimumab nine subjects (75%, three of which presented difficult to treat fistulas) experienced complete healing while the rest recorded an improvement (Tonelli et al, 2012). This suggests that a high local concentration of anti-TNF favors prompt and definitive healing, although definitive clinical trials are still needed (Tonelli et al, 2012;Ashcroft et al, 2012).…”

Section: Fistula Tract Injectionsmentioning

confidence: 97%

“…Pilot clinical studies utilizing local low-dose injections of antibody along the fistula tract have been found to be an effective experimental treatment for perianal fistulas in Crohn's disease. They used approximately 1/10th of the total antibody dose and were reported to be free from adverse events (Asteria et al, 2006;Taxonera et al, 2009;Tonelli et al, 2012). For instance, of 12 patients treated with locally injected Adalimumab nine subjects (75%, three of which presented difficult to treat fistulas) experienced complete healing while the rest recorded an improvement (Tonelli et al, 2012).…”

Section: Fistula Tract Injectionsmentioning

confidence: 98%

Targeted localized use of therapeutic antibodies: a review of non-systemic, topical and oral applications

Jones

Martino

2015

Critical Reviews in Biotechnology

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Therapeutic antibodies provide important tools in the "medicine chest" of today's clinician for the treatment of a range of disorders. Typically monoclonal or polyclonal antibodies are administered in large doses, either directly or indirectly into the circulation, via a systemic route which is well suited for disseminated ailments. Diseases confined within a specific localized tissue, however, may be treated more effectively and at reduced cost by a delivery system which targets directly the affected area. To explore the advantages of the local administration of antibodies, we reviewed current alternative, non-systemic delivery approaches which are in clinical use, being trialed or developed. These less conventional approaches comprise: (a) local injections, (b) topical and (c) peroral administration routes. Local delivery includes intra-ocular injections into the vitreal humor (i.e. Ranibizumab for age-related macular degeneration), subconjunctival injections (e.g. Bevacizumab for corneal neovascularization), intra-articular joint injections (i.e. anti-TNF alpha antibody for persistent inflammatory monoarthritis) and intratumoral or peritumoral injections (e.g. Ipilimumab for cancer). A range of other strategies, such as the local use of antibacterial antibodies, are also presented. Local injections of antibodies utilize doses which range from 1/10th to 1/100th of the required systemic dose therefore reducing both side-effects and treatment costs. In addition, any therapeutic antibody escaping from the local site of disease into the systemic circulation is immediately diluted within the large blood volume, further lowering the potential for unwanted effects. Needle-free topical application routes become an option when the condition is restricted locally to an external surface. The topical route may potentially be utilized in the form of eye drops for infections or corneal neovascularization or be applied to diseased skin for psoriasis, dermatitis, pyoderma gangrenosum, antibiotic resistant bacterial infections or ulcerated wounds. Diseases confined to the gastrointestinal tract can be targeted directly by applying antibody via the injection-free peroral route. The gastrointestinal tract is unusual in that its natural immuno-tolerant nature ensures the long-term safety of repeatedly ingesting heterologous antiserum or antibody materials. Without the stringent regulatory, purity and clean room requirements of manufacturing parenteral (injectable) antibodies, production costs are minimal, with the potential for more direct low-cost targeting of gastrointestinal diseases, especially with those caused by problematic antibiotic resistant or toxigenic bacteria (e.g. Clostridium difficile, Helicobacter pylori), viruses (e.g. rotavirus, norovirus) or inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease). Use of the oral route has previously been hindered by excessive antibody digestion within the gastrointestinal tract; however, this limitation may be overcome by intelligently applying one or more strate...

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“…Local injection of various substances and drugs has also been used for the treatment of CD fistula; the procedure is usually performed under general anesthesia, is well tolerated and minimally invasive without precluding other surgical options in case of failure. In order to avoid systemic toxicity, several authors in uncontrolled trails have assessed the feasibility of local infliximab [65][66][67] or adalimumab [68] therapy for perianal fistula with response in two-third of treated patients. Fibrin glue injection has been used in the healing of fistulas including perianal, but most of the studies include very few CD patients with a success rate ranging from 0 to 50% [69][70][71][72][73].…”

Section: Cd-related Fistulasmentioning

confidence: 99%

Endoscopic treatment of Crohn’s complications

Buda

Okolo

2014

Expert Review of Gastroenterology & Hepatology

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The progression to fistula and strictures is part of the natural history of Crohn's disease (CD) and these complications negatively affect the quality of life of CD patients. Surgery is the traditional treatment of CD strictures. However, due the chronicity of the inflammatory process and the associated fibrosis, postoperative recurrence occurs frequently. The lack of specific drug to treat fibrotic strictures and their irreversible nature has drawn the attention to less invasive and bowel-sparing therapeutic modalities. Endoluminal therapies may provide effective option in relieving symptoms associated with CD complications and reduce the need for repeated surgery with substantial clinical benefit. This review will discuss the current use and efficacy of the endoscopic treatment of CD complications. New endoscopic modalities and recent advances will be also evaluated.

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Effectiveness and Safety of Local Adalimumab Injection in Patients With Fistulizing Perianal Crohn’s Disease

Cited by 38 publications

References 27 publications

Modern management of perianal fistulas in Crohn’s disease: future directions

Modern management of perianal fistulas in Crohn’s disease: future directions

Targeted localized use of therapeutic antibodies: a review of non-systemic, topical and oral applications

Endoscopic treatment of Crohn’s complications

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