All patients with inflammatory bowel disease (IBD) should receive aggressive ongoing assessment of their inflammatory state and its response to immunomodulators, anti–tumor necrosis factor (anti-TNF) drugs, and other agents, according to multiple speakers at 2012 Advances in Inflammatory Bowel Diseases, the Crohn’s & Colitis Foundation’s Clinical & Research Conference, held this week in Hollywood, Florida.
The evolving treatment monitoring strategy for patients with IBD includes the following:
• Periodic assessment of patient symptoms with systematic scoring systems, such as the Crohn’s Disease Activity Index.
• Periodic assessment of objective endoscopic findings with systematic scoring systems that quantify the degree of objective inflammation, such as the Crohn’s Disease Endoscopic Index of Severity. Persistent active inflammation is the key determinant of the need for more aggressive strategies, such as with anti-TNF therapy. Bruce Sands, MD (Mount Sinai Medical Center, New York City), presented data that supported anti-TNFs as the most effective agents, especially when combined with immunomodulators. However, he emphasized the need to progress because of objective documentation of inflammation rather than infection or irritable bowel syndrome symptoms.
• Trough drug level monitoring for patients who are receiving anti-TNF therapy. The SONIC trial (2010) showed that inadequately dosed patients with IBD have undetectable trough blood levels of their anti-TNF drug; this predicts nonresponse, relapse, and worsening of inflammatory endoscopic findings (Stephen Hanauer, MD, University of Chicago).
• C-reactive protein (CRP) level measurement. Although CRP level is a nonspecific serum marker for systemic inflammation, monitoring it in patients before and during treatment may help in assessment of treatment response.
• Fecal calprotectin level. Although this measurement is expensive ($250 per assay), an elevated level correlates with active disease and a decreased level correlates with remissions.
• For nonresponders to anti-TNF therapy, check for the development of antibodies to the drug. If antibodies are positive, change to another anti-TNF agent rather than increase the dose of the current anti-TNF drug. If antibodies are negative, increase the dose or frequency of administration. Dr Hanauer suggested that this testing route will become more common as less costly antibody assays are developed. Before starting or changing to therapy with natalizumab, always check for John Cunningham virus and do not start the therapy if serologies are positive, because progressive multifocal leukoencephalopathy has been reported as a catastrophic adverse event with this agent (Corey Siegel, MD, Dartmouth Medical School, Hanover, New Hampshire).
• Cross-sectional imaging. CT enterography (CTE) and MR enterography (MRE) are advocated for sequential monitoring of patients with Crohn disease, where colonoscopy cannot assess the small bowel. Imaging has been shown to clarify clinical impressions of active inflammation and benefit from the use of corticosteroids in 61% of patients. Because of concerns about radiation exposure from sequential CT, its use should be limited in younger patients who may accumulate high lifetime exposure. How young is “too young” for periodic CTE? The answer is unclear, but Dr Loftus suggested a cutoff somewhere between age 35 and 50 years—patients older than the cutoff should undergo MRE, which delivers no radiation. Capsule enteroscopy also has a role in monitoring; it is more sensitive and specific for active small-bowel inflammation than CTE or MRE.
• Maintain a high degree of suspicion for infection, especially Clostridium difficile, if treatment appears to be “failing.” Many speakers warned the audience to think of infection rather than inflammation if IBD worsens despite therapeutic doses of effective immunomodulators or anti-TNF agents. Patients are at risk because they do receive antibiotics periodically, have ulcerated or fissured mucosa, and take immunosuppressive drugs. A consensus has emerged supporting fecal microbiota transplant as the most effective therapy, with 87% cure rates (R. Balfour Sartor, MD, University of North Carolina, Chapel Hill).