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previous TB infection or having undergone previous treatment for active TB or
latent TB infection [ 24 ]. There are no 100% specific or 100% sensitive methods for
diagnosing latent TB infection. All patients should have a tuberculin skin test (TST)
or interferon-γ release assay (IGRA) test and a chest X-ray as indicated for higher-
risk individuals. It is important to recognize that concurrent immunosuppressive
therapies such as corticosteroids are associated with anergy and false-negative skin
test results can occur [ 25 ]. It is generally recommended to replace the TST with
IGRA, which is more specific and sensitive [ 24 ]. Patients screening positive for
latent TB should begin a 6-month course of antituberculosis therapy prior to initia-
tion of biologic therapy, and while the duration of treatment for latent TB prior to
initiation of anti-TNF therapy has not been definitively defined, common practice
suggests at least 1 month of antituberculosis therapy prior to anti-TNF therapy is
prudent in most cases.
Anti-TNF therapy may increase the risk of reactivation of HBV in patients who
are chronic carriers of this virus. Guidelines recommend screening all patients for
HBV prior to starting anti-TNF therapy. Serologic assessment for HBV should
include hepatitis B surface antigen (HBsAg), hepatitis B surface antibody
(HBsAb) with levels, and hepatitis B core antibody (HBcAb). If active HBV is
found, it should be treated and controlled before anti-TNF initiation. In
HBsAg + carrier patients, prophylactic antiviral treatment is recommended and
ideally started at least 2 weeks prior to the introduction of anti-TNF therapy and
continued for at least 6 months after its cessation [ 23 , 26 ] to reduce the risk of
HBV reactivation.
Anti-integrin Therapy
Clinical trial data suggest that anti-integrin therapies overall have a favorable safety
profile, with low rates of serious infections over an extended treatment period [ 27 ].
However, the occurrence of progressive multifocal leukoencephalopathy (PML)
due to reactivation of John Cunningham (JC) virus in approximately 1:1000 patients
treated with natalizumab both in clinical trials and in post-marketing surveillance
has limited the uptake of natalizumab for Crohn’s disease. Risk factors for PML
include positive JCV antibody status at baseline, concomitant immunosuppression,
and more than 2 years of exposure to natalizumab [ 28 ]. Therefore, testing for JCV
prior to starting natalizumab can identify those patients at lowest risk (i.e., negative
antibody status) for subsequent PML. Furthermore, patients treated with natali-
zumab should not be on concomitant immunosuppressives, and those on concomi-
tant steroids should be weaned off of steroids within 6 months of initiation of
natalizumab [ 17 ].
Although natalizumab and vedolizumab are both anti-integrins that prevent leu-
kocyte adhesion via blockade of α4 integrin, vedolizumab is more selective due to
additional β7 inhibition which is specific to leukocyte trafficking to the gut. To date,
no cases of PML have been reported in patients receiving vedolizumab [ 29 ], and
JCV testing is not indicated prior to initiation of vedolizumab therapy.
L. Zhu and G.Y. Melmed