Anti-tumor necrosis factor therapy (anti-TNF) has emerged as an effective treatment for IBD[20-23
]. It, however, carries risk of infection due to immunosuppression. The incidence of reactivation of latent tuberculosis infection (LTBI) has been shown to be increased among individuals treated with anti-TNF. A review of the United States Food and Drug Administration Adverse Eve nt Reporting System found an incidence of 24 cases of tuberculosis per 100000 per year among those treated with anti-TNF, which translates into a 4 fold increased risk[24
]. Similarly, the incidence of hepatitis B virus (HBV) reactivation is also increased among these patients[25-27
In order to minimize this risk, screening measures have been recommended prior to initiating anti-TNF therapy. Screening for LTBI and HBV prior to treatment has been recommended by the United States Food and Drug Administration, Health Canada, and all gastrointestinal societies[28-31
]. Screening is effective in reducing infections complications, is easy to perform, and has minimal risks to patients[32-34
]. This involves tuberculin skin testing and chest-X-ray for LTBI and a panel of three serological blood tests for HBV (HBsAg, HBsAb, HBcAb). Adherence to screening with tuberculin skin testing and chest x-ray has been shown to reduce the risk of tuberculosis by 78%-90%[32,33
]. Screening for HBV with subsequent vaccination or chemoprophylaxis if indicated has also been shown to be effective[34
Despite these recommendations, cases of severe and sometimes fatal infection with tuberculosis or hepatitis B have been described, and many of these can be attributed to lack of screening[34-36
]. A retrospective review of over 200 patients followed at a large United States academic IBD center revealed only 65% of patients were appropriately screened for tuberculosis and 25% screened for hepatitis B[37
]. Similarly, a study from Australia showed that only 50% of gastroenterologists were routinely screening for HBV prior to starting anti-TNF[38
]. This underscores the problem in provider’s adherence to screening. The development of tuberculosis or hepatitis B while on anti-TNF has the potential for high morbidity and mortality. Given the ease and effectiveness of screening and the consequences of lack of screening, one can argue that anti-TNF screening rates less than 100% are unacceptable.
There is growing literature exploring contributors to this safety problem. In their review of 287 IBD patients starting anti-TNF, Vaughn et al[37
] identified factors most often associated with lack of screening for tuberculosis: previous exposure to anti-TNF [OR = 5.3 (95%CI: 2.8-10.3)], health care providers in practice for more than 10 years [2.5 (95%CI: 1.4-4.5) and treatment at a non-IBD center [1.9 (95%CI: 1-3.4)]. The factors contributing to lack of HBV screening were the same. These reasons highlight the role of lack of knowledge, as physicians in practice longer or those at a non-IBD center may be less likely to be up to date with current guidelines. Previous exposure to anti-TNF may falsely reassure the prescribing physician that the appropriate work up had already been completed. This highlights the contribution of confusion as to who is responsible for screening. Uncertainty as to how and when to screen is also an important contributor, as evident in a gastroenterology practice audit that showed that while most knew that screening was indicated, there was significant heterogeneity in the type and timing of screening[38
]. Thus, knowledge gaps as to the need for screening, confusion surrounding responsibility for screening, and details regarding how to screen appear to be major contributors to this problem.