Monitoring

Patients with Crohn disease (CD) should be seen by a gastroenterologist on a routine basis to monitor for complications and flares of the disease and adjust treatment accordingly. Patients with uncomplicated cases of CD need follow-up visits every 6 months, while those on azathioprine or mercaptopurine require visits on a 3-month basis. Telemedicine has also been shown to be a safe method of follow-up, which may minimize need for outpatient visits and help reduce hospital admissions.[308][309]​​​

To minimize the risk of iatrogenic complications, guidelines recommend baseline blood-test screening prior to initiation of all non-nutritional treatments and regular monitoring, to exclude sepsis and pre-existing renal or liver impairment.[110] Drugs can cause nephrotoxicity or hepatotoxicity.

Particular mention should be made of immunomodulators (azathioprine, mercaptopurine, methotrexate, and tumor necrosis factor [TNF]-alpha inhibitors), which can produce life-threatening consequences if started without due caution.

Monitoring for patients treated with immunomodulators

Immunomodulators should never be started if there is any indication of sepsis. Before commencing azathioprine or mercaptopurine, it is advisable to measure the patient's blood thiopurine S-methyltransferase level to assess susceptibility to toxicity. Blood counts and liver function tests require close monitoring during treatment. Previous exposure to common viruses, such as varicella zoster (chickenpox), may be checked by antibody testing prior to initiation of azathioprine.[116] Before commencing methotrexate, it is important to measure complete blood count and renal and liver function, and these should be monitored regularly while on treatment.

In patients who relapse on thiopurine maintenance therapy, thiopurine metabolite testing (6-thioguanine nucleotide [6-TGN] and 6-methylmercaptopurine [6-MMP]) can guide dose optimization and likelihood of side effects.[229]

Thiopurine metabolites can also be used to:[230]

  • Assess compliance to therapy

  • Detect sub/supra therapeutic dosing

  • Identify resistance to thiopurines or the need to add allopurinol (in patients who are hypermethylators of thiopurines), or

  • Investigate possible thiopurine side effects

The British Society of Gastroenterology suggests checking metabolites in patients with newly abnormal liver function tests or myelotoxicity, and using results to alter dosing (or stop the drug) as necessary.[70] However, routine measurement of metabolites has not been shown to be beneficial, due to wide variations in levels reported.[231] Prospective studies show a lack of clinical benefit.[232][233][234]

Monitoring for patients treated with TNF-alpha inhibitors

TNF-alpha inhibitor agents are associated with an increased risk of developing tuberculosis (TB).[117][310] Patients should be screened with a combination of history-taking, chest x-rays, an interferon-gamma release assay blood test, and/or a tuberculin skin test if deemed high risk. Reactivation of hepatitis B has been reported, with a theoretical risk of reactivation of hepatitis C; patients with CD should be tested for serologic markers of hepatitis B and hepatitis C before treatment is initiated.[120][121] In clinical practice, the same TB precautions are taken for those starting newer biologic agents as those starting TNF-alpha inhibitor therapies. This is despite the fact that data suggest that biologics have favorable safety profiles with low risk of adverse events.[110]

Antibodies to TNF-alpha inhibitor therapies are a potential concern as they may lead to loss of clinical response and lower serum levels.[163][164]

Therapeutic monitoring of TNF-alpha inhibitors can be done by testing the serum level of circulating drug (trough level, taken before the next dose is due). This may allow dose adjustment if levels are too high. If levels are too low, additional testing for anti-TNF antibody levels can be done, where their presence may render any dose escalation futile and inadvisable and may encourage a switch to an alternative agent. This can be done in two groups of patients, those who lose response to TNF-alpha inhibitor treatment, and those who are maintained on treatment and could benefit from sustained treatment.

Guidelines do not recommend proactive therapeutic drug monitoring in those in clinical remission or for those who have lost response to a TNF-alpha agent.[110][246] Further research is required regarding the best method to measure TNF-alpha inhibitor levels, the reference standards, the accuracy for predicting clinical state, and clinically meaningful thresholds.[247] One trial compared proactive therapeutic drug monitoring (individualized, scheduled monitoring of serum drug levels) with standard infliximab therapy in patients with immune-mediated inflammatory diseases, including CD. Patients who received therapeutic drug monitoring were more likely to sustain disease remission compared with patients who received standard care (73.6% vs. 55.9%).[248] The National Institute for Health and Care Excellence in the UK has evaluated a commercially available enzyme-linked immunosorbent assay (ELISA) as a technology for this purpose for centers where TNF levels and antibody levels are performed.[249]

Monitoring for patients treated with immunosuppressants and corticosteroids

Patients on immunosuppressants and corticosteroids should receive routine evaluation and testing with regard to drug levels and complications of the treatment. Bone mineral densitometry scanning (dual energy x-ray absorptiometry) should be considered in all patients with CD, due to the higher risk of osteoporosis. Patients at particularly high risk fall into two groups as follows:

  • Patients ages <65 years, receiving prolonged courses of corticosteroids (>3 months per year)

  • Patients who have continuing active disease, are underweight (body mass index <20 kg/m²), ages >75 years, or with weight loss >10% from baseline

Monitoring for malabsorption

Patients should be monitored for evidence of malabsorption, with diet adjustments and supplementations given accordingly. Serum B12 levels should be monitored in patients with ileal CD and in those with ileal resection.

Cancer surveillance

Patients with CD have more than twofold increased risk of developing colon cancer.[280]​ Patients who have had the disease for more than 8 years, or who have predominantly colonic disease, are at greater risk. Surveillance colonoscopy screening is recommended for patients with CD; those with colonic disease are likely to benefit most from surveillance.[311][312][313][314]​​ [ Cochrane Clinical Answers logo ] ​ Patients with CD are also at higher risk of developing squamous cell carcinoma of the anus, duodenal neoplasia, and lymphoma. There is some evidence to say that patients with perianal CD are at increased risk for developing colorectal and anal cancer.[315]

Where dysplasia (precancerous change) is found in a patient with inflammatory bowel disease, management options include enhanced surveillance, endoscopic resection or prophylactic surgery depending on the individual situation.[316]

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