Reviews in gastroenterological disorders最新文献

The current guidelines for the management of Crohn's disease (CD) suggest a stepwise approach to treatment according to the severity of clinical presentation. The use of tumor necrosis factor (TNF) antagonists are currently reserved for patients who do not respond to conventional nonbiological therapies such as corticosteroids and immunosuppressants. However, as TNF-alpha antagonists have the potential to produce mucosal healing in CD, earlier more aggressive treatment with biologics has been advocated. Anti-TNF therapy may be most beneficial in the early stages of inflammatory disease, before patients develop complications such as fibrostenotic or penetrating disease. Thus, the use of the more aggressive "top-down" strategy involving early introduction of biologics has been explored. Emerging data suggest that earlier use of biological therapy is associated with improved clinical outcomes and potential disease-modifying effects. Future studies are warranted and will likely lead to the expanded use of such agents in the treatment of CD.

With the introduction of biologic therapies for inflammatory bowel disease, significant questions have arisen regarding their best optimization. Although initial recommendations were to combine immunosuppressives with biologics to reduce immunogenicity, trials with 3 different anti-tumor necrosis factor agents (infliximab, adalimumab, and certolizumab) and a humanized monoclonal antibody that targets alpha-4 integrins (natalizumab) have failed to demonstrate the clinical superiority of combination therapy when high-dose induction and scheduled maintenance therapy was prescribed for up to 1 year. However, immunosuppressive agents should be considered with episodic biologic therapy to decrease immunogenicity and secondary loss of response. The issue of whether induction with biologics and maintenance therapy with immunosuppressives as monotherapy is as safe and effective as induction and maintenance with biologics alone still remains to be addressed. Further, with the use of concomitant immunosuppressives and biologics, evolving data raise concerns for an increase in adverse events, including opportunistic infections, neurological disorders, and cancer. Specific therapeutic decisions need to be individualized and the clinician must help the patient weigh quality-of-life issues with readiness to assume possible risks.

The introduction of anti-tumor necrosis factor-a 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.

The most recent European Helicobacter Study Group consensus recommendations are a state-of-the-art evaluation of the literature on Helicobacter pylori. The traditional indications for H. pylori eradication remain the major indications for eradication therapy in 2007. A role for H. pylori infection has been demonstrated in disease states that were not traditionally thought to be related to H. pylori infection, namely iron deficiency anemia unexplained by other causes, and idiopathic thrombocytopenic purpura. Office-based H. pylori tests are no longer recommended by the consensus group because of their poor sensitivity and specificity in clinical practice. The treatment of H. pylori infection has not changed significantly in the last decade, though promising alternatives are being studied. At present the treatment regimen recommended for world-wide use is triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin. Culture and antimicrobial sensitivity testing are recommended in areas where resistance rates to clarithromycin are high.