From these total results, 1 year of IFX treatment after surgery was effective for preventing endoscopic and histologic recurrences of CD, but some clarifications should be made

From these total results, 1 year of IFX treatment after surgery was effective for preventing endoscopic and histologic recurrences of CD, but some clarifications should be made. of biologics may improve patient outcomes in active CD. However, a widespread use of a top-down approach in all CD patients cannot be recommended. Clinical factors at diagnosis may predict poor outcome in CD, and should be taken into account when determining the initial therapeutic approach. = 0.0025). Ocular manifestations developed in 2%C6% of patients with IBD, with the most common being episcleritis and uveitis. Many case reports and pilot studies have demonstrated that IFX can suppress uveitis and scleritis associated with various autoimmune disorders, including IBD. Predictors Mmp10 of response in luminal and fistulizing CD Smoking and concomitant use of immunosuppressive drugs appear to have an important influence on the initial response and durability of response in patients with inflammatory disease. A study from the Cleveland Clinic included 100 patients with inflammatory or fistulous CD who were followed for at least 3 months after treatment.43 In those with inflammatory disease, an initial response was significantly more likely in nonsmokers (73% vs 22%) and in those taking concurrent immunosuppressive medications (74% vs 39%). A prolonged response (more than BN82002 2 months) was also more likely in nonsmokers (59% vs 6%) and in those taking concomitant immunosuppressive medications (65% vs 18%). For those with fistulous disease, overall response rates were no different between smokers and nonsmokers, but nonsmokers had a longer duration of response. Patients with isolated colonic disease,44 those of young age,45 those with endoscopic evidence of ileocolonic ulcers at BN82002 baseline, and those with an elevated C-reactive protein had a better response, whereas BN82002 those with stricturing disease46 or previous abdominal disease47 were less likely to respond.48 Safety Although short- and long-term anti-TNF- therapy is generally well tolerated, clinicians must be vigilant for BN82002 the occurrence of infrequent but serious adverse events (see Table 2). A long-term report of safety data over a 14-year period reported a 13% rate of severe adverse events vs 19% in placebo group. A recent review compared the rate of different adverse events among biologics and placebo, and concluded that serious adverse events such as infections, lymphoma, and congestive heart failure did not have a significantly different incidence between biologics and control treatment. IFX was associated with a significantly higher risk of withdrawals due to adverse events compared with controls (odds ratio: 2.04, 95% CI: 1.43C2.91; number needed to harm = 12, 95% CI: 8C28).49 Safety data from the SONIC trial demonstrated that the rate of adverse events was similar among the IFX monotherapy, IFX plus azathioprine, and azathioprine monotherapy groups. Infusion reactions occurred less frequently among patients receiving combination therapy but the risk of opportunistic infections increases when TNF- therapy is combined with additional immunosuppressive treatment. Table 2 Adverse events associated with infliximab use Infections (opportunistic and mycobacterial)Cytokine release reactionsAutoimmunity (formation of antinuclear and DNA antibodies)MalignanciesHeart failureDemyelinationLiver function abnormalitiesDermatologic complications (psoriasis and other skin lesions) Open in a separate window A report from the Mayo Clinic described the clinical experience in 500 patients who received a median of three infusions and were followed up for a median of 17 months.50 Although the authors concluded that therapy was generally well tolerated, they warned that clinicians using IFX should be vigilant for the occurrence of infrequent but serious adverse events, particularly in elderly patients. A more recent paper reports that patients older than 65 years treated with TNF inhibitors for IBD have a high rate of severe infections and mortality compared with younger patients or patients of the same age who did not receive these drugs.51 The most important concerns with prolonged use of biologics are related to cancer risk. A recent multicenter, matched-pair study assessed whether IFX use in CD for a median of 6 years is associated with an increased frequency of neoplasia in the long term. The authors concluded that the frequency of neoplasia was comparable in an adult population of CD patients treated or not with IFX.52 Toxicity can be BN82002 significantly reduced by routine tuberculosis screening, and by avoiding anti-TNF agents in patients with heart failure, chronic infections, or previous neoplastic disease. Prospective, observational studies with longer follow-up, such as the TREAT registry,53 will continue to provide more useful information on this issue, and clinicians need to remain aware of the potential for serious adverse events during longer-term exposure beyond the confines of clinical trials. Patients with intestinal strictures due to.