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Volume 7, Supplement 1, 2007

Volume 7, Supplement 1, 2007

Table of Contents

Biologic Therapy in Crohn’s Disease: Review of the Evidence Refining the Role of TNF Antagonists
It is expected that within a few months, there will be commercially available in the United States a total of 3 biologic agents with inhibition of tumor necrosis factor- (TNF-) as the primary mechanism of action: infliximab, adalimumab, and certolizumab pegol. The primary efficacy data for each of these agents are reviewed. All 3 agents appear to be efficacious for both induction and maintenance of remission in Crohn’s disease. There are no trials comparing these agents, but one can infer from available data that they have broadly similar efficacy. Adverse events associated with anti-TNF- therapy, including infection, infusion reactions, autoimmunity, risk of malignancy, and neurologic events, are reviewed. [Rev Gastroenterol Disord. 2007;7(suppl 1):S3-S12]
Serologic and Prognostic Biomarkers: Who, When, and How? Clinical Perspectives in Crohn’s Disease
The introduction of anti-tumor necrosis factor- therapies has significantly expanded the armamentarium for patients with inflammatory bowel disease (IBD). Clinical experience has shown that not all patients respond to therapies in this class, which emphasizes the hypothesis that there are different pathways involved in the inflammatory cascade characteristic of the spectrum of IBD phenotypes. The broadening of therapeutics with different mechanisms of action and targets is important for patients with IBD. Based on evidence gathered in recent studies, the key to success with these therapies may lie in targeting the right patients based on knowledge of their underlying genetic defects and resultant immune reactivity. Determining the factors that can predict the progression from uncomplicated to complicated disease states may stratify patients into at-risk populations and have an impact on their ultimate therapeutic management. [Rev Gastroenterol Disord. 2007;7(suppl 2):S3-S7]
Objective Measures of Disease Activity: Alternatives to Symptom Indices Clinical Perspectives in Crohn’s Disease
Advances in fecal and serum inflammatory biomarkers, endoscopy, and radiology have led to a rapid expansion of modalities for diagnosis and disease activity assessment of Crohn’s disease. Although no test is recognized as the most accurate for assessing disease activity, ileocolonoscopy remains the single test that may approach the gold standard for clinical diagnosis. Serum Creactive protein concentrations have been shown to correlate reasonably well with clinical, endoscopic, and radiologic measures of disease activity, and they appear to have prognostic value in certain settings. Fecal markers of inflammation, such as lactoferrin and calprotectin, are relatively noninvasive ways to determine disease activity and predict clinical relapse. Capsule endoscopy allows visual inspection of previously inaccessible areas of the small intestine and may serve as a useful tool for patients with suspected small bowel involvement but negative results on conventional testing. Computed tomographic (CT) enterography, which entails ingestion of a large volume of a neutral or negative contrast agent and scanning protocols that take advantage of the differences in contrast between the lumen and the bowel wall, appears to be more sensitive than small bowel follow-through for detecting small bowel Crohn’s disease and provides extraluminal information. Magnetic resonance enterography employs principles similar to those of CT enterography without exposure to ionizing radiation, and early results are encouraging. We are beginning to accumulate evidence that treatment based on objective measures such as mucosal healing might affect long-term outcomes, but prospective trials of objective marker-directed therapy are required to confirm this hypothesis. [Rev Gastroenterol Disord. 2007;7(suppl 2):S8-S16]
TNF-Alpha Antagonists: Benefits Beyond Remission Refining the Role of TNF Antagonists
Medical options for Crohn’s disease are expanding at an unprecedented rate. The anti–tumor necrosis factor-a (TNF-a) agents infliximab, adalimumab, and certolizumab pegol have proven efficacy for induction and maintenance of remission among patients with moderate to severe Crohn’s disease. Anti- TNF therapy has also been successful in reducing the need for corticosteroids, closing fistulas, healing colonic mucosa, and reducing the number of hospitalizations and surgeries. With these tools, the goal of therapy in Crohn’s disease may change from the management of symptoms to a change in the natural history of the disease. [Rev Gastroenterol Disord. 2007;7(suppl 1):S13-S19]
Turning Traditional Treatment Strategies on Their Heads: Current Evidence for “Step-Up” Versus “Top-Down” Clinical Perspectives in Crohn’s Disease
The current Crohn’s disease treatment algorithm involves a “step-up” approach in which conventional medications such as corticosteroids are given first and anti–tumor necrosis factor- (TNF-) agents are reserved for refractory cases. Although this approach may seem to be cost-efficient, recent studies have shown that “top-down” therapy using anti–TNF- agents in newly diagnosed patients improves long-term rates of mucosal healing, a therapeutic endpoint that correlates with reduced hospitalizations and surgeries, thereby reducing overall costs and enhancing patients’ quality of life. Another reason the step-up approach has been favored over the top-down is concern about side effects; however, a multivariate logistic regression analysis of patients treated with or without infliximab showed no differences in mortality, serious infections, or malignancies between the 2 groups. Moreover, newer anti-TNF- agents, such as adalimumab and certolizumab pegol, have the potential to reduce the risk of immunogenicity and the associated infusion reactions and loss of response, as well as reducing autoimmunity associated with infliximab therapy. The potential advantages of “reversing” our current therapeutic pyramid/algorithm for the treatment of Crohn’s disease include early disease stabilization and disease modification, minimization of complications such as strictures and fistulae that lead to the need for surgery, reduction of postoperative recurrence, and avoidance of the ubiquitous complications of corticosteroid therapy. [Rev Gastroenterol Disord. 2007;7(suppl 2):S17-S22]
Crohn’s Disease in Patients Who Fail Infliximab Therapy: What Does the Future Hold? Refining the Role of TNF Antagonists
Patients who respond to infliximab enjoy many benefits, including improvement in clinical symptoms, less disability, and a better quality of life. Unfortunately, many patients are unresponsive to infliximab therapy. They may be completely refractory to infliximab therapy (ie, primary nonresponders), they may have shown an initial response to therapy that subsequently diminished, or they may be hypersensitive to the drug. For these patients, second-generation tumor necrosis factor (TNF) inhibitors will soon be available; adalimumab and certolizumab pegol are the two agents most likely to gain Food and Drug Administration approval for the treatment of Crohn’s disease. This article looks at recent studies using these newer TNF inhibitors in patients in whom infliximab treatment has failed as well as in those who have never received infliximab. [Rev Gastroenterol Disord. 2007;7(suppl 1):S20-S26]
Moving Forward With Anti-TNFAlpha Therapy: Current Needs and Future Treatments Clinical Perspectives in Crohn’s Disease
Although infliximab continues to make an important contribution to the management of Crohn’s disease, its use includes several clinical challenges, including loss of response, loss of tolerability due to acute and delayed infusion reactions, and the need for intravenous administration by a health care provider. Newer anti–tumor necrosis factor- agents such as certolizumab pegol and adalimumab have been shown in clinical trials to have similar efficacy as infliximab, without the acute and delayed infusion reactions. Further information is needed about infliximab, certolizumab pegol, and adalimumab so we can understand the relationships among these 3 agents in terms of antibody formation, drug concentration, dosing (episodic vs systematic maintenance), concomitant immunosuppressive therapy, and efficacy. [Rev Gastroenterol Disord. 2007;7(suppl 2):S23-S35]
Self-Assessment Post-Test Clinical Perspectives in Crohn’s Disease