Therapeutic drug monitoring of infliximab in inflammatory bowel disease patients in a teaching hospital setting: results of a prospective cohort study.

OBJECTIVE: Therapeutic drug monitoring (TDM) of infliximab (IFX) is not routinely implemented in our clinical practice. We therefore carried out a prospective cohort study measuring IFX trough levels in our total inflammatory bowel disease (IBD) population in relation to remission. METHODS: Patient demographics, and medication and clinical history were collected from the electronic hospital information system. Blood was drawn at one time point for the determination of IFX trough levels and antibodies to IFX (ATI). Disease activity indices [Crohn's disease activity index (CDAI) and the Truelove-Witts disease activity index (TWDAI) for Crohn's disease and ulcerative colitis, respectively] and quality-of-life scores (Visual Analog Scale) were obtained. RESULTS: We included 107 patients. IFX levels varied from less than 0.02 to 21.9 µg/ml. The median IFX level was 2.8 µg/ml [interquartile range (IQR) 1.37-5.13]. The IFX level was associated significantly with remission (P=0.007). The median IFX level was 3.9 µg/ml (IQR 1.9-6.53) in patients in remission and 2.1 µg/ml in patients with active disease (IQR 0.77-4.38) (P=0.074). Receiver operating charecteristic curve analysis indicated a cutoff value of 2.18 µg/ml for CD and 6.26 µg/ml for UC. Eleven patients (10.3%) had developed ATI. The appearance of ATI was associated with the disappearance of IFX [relative risk: 2.2 (95% confidence interval: 1.368-3.610) P<0.0001], but not with relapse. The presence of ATI induced more infusion reactions [relative risk: 11.7 (95% confidence interval: 2.74-49.60) P<0.001]. CONCLUSION: TDM of IFX in IBD outpatients in a teaching hospital setting showed large interindividual differences in IFX trough levels. Despite this, we still found a significant association between remission and IFX trough levels. We determined cutoff values for both IBD modalities. IFX trough levels were not detectable in a significant proportion of IBD patients; TDM is indicated to identify this group of patients.

The tuberculin skin test is unreliable in school children BCG-vaccinated in infancy and at low risk of tuberculosis infection.

BACKGROUND: The tuberculin skin test (TST) is often used to screen for latent tuberculosis infection (LTBI) in school children, many of whom were bacille Calmette-Guérin (BCG)-vaccinated in infancy. The reliability of the TST in such children is unknown. METHODS: TSTs performed in low-risk BCG-vaccinated and -nonvaccinated grade 1 and grade 6 First Nations (North American Indian) school children in the province of Alberta, Canada, were evaluated retrospectively. To further assess the specificity of the TST, BCG-vaccinated children with a positive TST (≥10 mm of induration) and no treatment of LTBI were administered a QuantiFERON-TB Gold In-Tube test (QFT-GIT, Cellestis International). RESULTS: A total of 3996 children, 2063 (51.6%) BCG-vaccinated and 1933 (48.4%) BCG-nonvaccinated, were screened for LTBI. Vaccinated children were more likely than nonvaccinated children to be TST positive (5.7% vs. 0.2%, P < 0.001). Vaccinated children with a positive TST were more likely to have a recent past TST as compared with those with a negative TST (6.8% versus 2.8%, P = 0.01). Among 65 BCG-vaccinated TST-positive children who underwent a QFT-GIT, only 5 (7.7%; 95% CI: 2.5%, 17.0%) were QFT-GIT positive. A TST of ≥15 mm was more likely to be associated with a positive QFT-GIT than a TST of 10 to 14 mm, 16.0% (95% CI: 4.5%, 36.1%) versus 2.5% (95% CI: 0.1%, 13.2%), P = 0.047. CONCLUSION: The TST is unreliable in school children, BCG-vaccinated in infancy, and who are at low risk of infection. The QFT-GIT is a useful confirmatory test for LTBI in BCG-vaccinated TST-positive school children.

Mycobacterium tuberculosis infection in First Nations preschool children in Alberta: implications for BCG (bacille Calmette-Guérin) vaccine withdrawal.

BACKGROUND: On April 1, 2004, BCG (bacille Calmette-Guérin), a tuberculosis (TB) control vaccine, was discontinued in all but four high-risk communities in Alberta. To confirm the safety of vaccine withdrawal, and for future planning, the annual risk of infection (ARI) was determined in preschool First Nations children. METHODS: First Nations children born into reserve communities in Alberta between April 1, 1998 and March 31, 2004, and still living on reserve in 2004-2005, were identified. Health centre TB histories were validated by cross-referencing the birth cohort with the provincial TB Registry. Children that were not BCG vaccinated and not known to be tuberculin skin test (TST) positive underwent a TST. Birth cohort children were grouped as follows: (i) BCG vaccinated; (ii) BCG non-vaccinated, no TST; (iii) BCG non-vaccinated, TST; (iv) BCG vaccination status unknown. The ARI was calculated and the age and community characteristics of the groups were compared. RESULTS: There were 8447 children in the 6-year birth cohort, 4699 (55.6%) vaccinated, 2696 (31.9%) non-vaccinated, and 1052 (12.5%) whose vaccination status was unknown. Of the non-vaccinated children, 1921 (71.3%) were tested and only 2 were TST positive. No other TST positive, BCG non-vaccinated children were identified in the TB Registry cross-match. The prevalence of infection in 2004-2005 was 0.1% and the ARI was 0.03%. The community risk of TB exposure was comparable in tuberculin-tested and non-tested BCG non-vaccinated children. CONCLUSION: In low BCG-uptake First Nations communities in Alberta, the ARI is low and it is safe to withdraw BCG.