Tuberculosis In Inflammatory Bowel Disease Patients Research Articles

Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America.

BACKGROUNDThere has been an increase in cases of inflammatory bowel disease (IBD) in recent years. There is also greater access and availability of immunosuppressive and biological agents, which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing. Tuberculosis (TB) remains a public health problem, and it has a high incidence in several countries. Therefore, knowledge of the risk of developing TB in patients with IBD is important.AIMTo evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America.METHODSA standard questionnaire included demographic variables, clinical aspects of IBD disease, history of active TB during treatment, active TB characteristics and evolution, initial screening and results and time from the start of anti-tumor necrosis factor alpha (TNFα) to TB development.RESULTSAzathioprine, anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence. The TNFα blockers increased the relative risk of developing active TB compared to other treatments. All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB. After adjustment for sex, age, type of IBD and latent TB, anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment. Late TB, which was diagnosed 3 mo after the start of anti-TNFα, was the most frequent.CONCLUSIONTreatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America. This risk was increased when anti-TNFα was combined with azathioprine. The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection.

Higher risk of tuberculosis in combination therapy for inflammatory bowel disease: A nationwide population-based cohort study in South Korea.

Inflammatory bowel disease (IBD) in Asia has become increasingly prevalent. As a treatment of IBD, many immunomodulators and biological agents were introduced and shown to be effective in inducing and maintaining remission. However, many cases with treatment failure were reported. To overcome the failure, combination therapy of immunomodulatory and biologics have emerged, showing better outcomes by optimizing biologic pharmacokinetics and minimizing immunogenicity. Adversely, rates of tuberculosis (TB) have been increased as a result. The aim of this study is to compare the risk of TB according to the therapy using large population data.We used data from the South Korean Health Insurance and Review Agency over the period 2008–2016 and calculated the hazard ratio (HR) for TB in IBD. We compared the risk of TB according to the medication: infliximab only, azathioprine only (AZA), combination of azathioprine and infliximab (CAI), azathioprine monotherapy and infliximab monotherapy (AIM), and azathioprine and infliximab whether simultaneously or separately (AISS).In IBD patients, a total of 249 patients were identified as active TB. After one-to-one matching with age, sex and disease duration, the risks of TB were significantly higher in AZA group (HR, 2.06; 95% CI, 1.35–3.12, P < .001), AIM group (HR, 3.26; 95% CI, 1.18–9.05, P = .02), AISS group (HR, 3.50; 95% CI, 1.92–6.37, P < .001), and CAI group (HR, 5.67; 95% CI, 2.42–10.21, P < .001), and the HR increased gradually in this order. In UC patients, the results were in similar pattern, but this pattern was not observed in CD patients in our study.Our study shows that Korean IBD patients are at risk of TB, and the risk increases with usage of IBD medication; moreover, the risk is the highest if combination therapy is used. These results highlight the importance of screening for TB in IBD patients, especially in combination therapy.

P809 Increase of tuberculosis due to combination therapy in inflammatory bowel disease: a nationwide population-based study in Korea

Abstract Background Recent researches reported that inflammatory bowel disease (IBD) in Asia has become more prevalent. Since IBD is chronic inflammation disorder and its relapse is frequent, obtaining and maintaining remission is important. As our knowledge on the pathogenesis of IBD deepened, many immunosuppressants and biological agents were introduced and confirmed to be both safe and effective. However, biologics known as anti-tumour necrosis factor (anti-TNF) agents was reported to lose response over time in 23–46% of patients. Therefore, combination therapy adding immunomodulator drug such as azathioprine was introduced and showed better outcome by optimising biologic pharmacokinetics and minimising immunogenicity. Adversely, rates of tuberculosis are increased, but there is no large population data estimating and comparing these risk in combination therapy. Methods We used 2008–2016 data of the South Korean Health Insurance and Review Agency (HIRA), and odd ratio (OR) for tuberculosis in IBD patients who underwent anti-tumour necrosis factor (TNF) agent, azathioprine, or combination therapy. Results Between 2008 and 2016, 47,760 patients were newly diagnosed as IBD, 29,440 as UC and 15,320 as CD. We compared the risk of tuberculosis according to the medication divided into 5 groups; infliximab only, azathioprine only, combination of azathioprine and infliximab, azathioprine monotherapy and infliximab monotherapy, and azathioprine and infliximab whether simultaneously or separately. We also compared the risk between male and female. Hazard ratio of tuberculosis in infliximab monotherapy, azathioprine, and combination therapy in IBD patients were 1.132, 1.256, and 2.118, respectively. Conclusion Our study shows that Korean IBD patients are at risk for tuberculosis, and this results may highlight the importance of screening for tuberculosis in IBD patients.

P077 Tuberculosis in inflammatory bowel disease patients from a referral center in Salvador-Bahia, Brazil

BACKGROUND: In the last decade, potent immunosuppressive therapy has become the standard treatment for inflammatory bowel disease (IBD) (1). However, the increasingly use of immunomodulators associated to biological therapy—especially the inhibitors of tumor necrosis factor alpha (TNF-α)—have considerably increased the cases of tuberculosis (TB) in IBD patients (2,3). Meanwhile, Brazil is a high TB burden country, with 87,000 new cases per year, and the state of Bahia reports more than 3,600 new cases annually (4,5). METHODS: Were included IBD patients under treatment followed at a referral center from August 2017 to July 2018. The IBD was diagnosed according to the guideline criteria of was according to the criteria the European Crohn's and Colitis Organizsation. Diagnosis of latent TB infection (LTBI) was based on tuberculin skin test (TST) induration ≥5 mm without evidence of clinically manifested active tuberculosis (TB). The development of active TB, diagnosed during the treatment for inflammatory bowel disease, was based on symptoms, TST, chest X ray and laboratory finding. In addition, Sstatistical analysies was performed using the statistical software package SPSS version 21.0 for Windows. A P-value less than 0.05 was considered statistically significant. RESULTS: Of the 302 patients evaluated, 185 were submitted to screening for LTBI and 24 (12.9%) were positive. Of the total sample, 8 (2.6%) developed active TB during treatment for IBD. Six cases occurred despite theof negative screening for LTBI and 2 cases occurred even after chemoprophylaxis with isoniazid. Among 186 UC patients, 4 (2.1%) developed active TB and all cases were pulmonary TB. Two patients were under azathioprine monotherapy (?) with azathioprine and 2 were using 5-ASA derivatives without immunosuppressant. Among 116 Crohn disease (CD) patients, 4 (3.4%) developed active TB, 2 cases of pulmonary TB and 2 cases of pleural TB. All patients with CD who developed active TB were under anti-TNF therapy, 2 under treatment with infliximab monotherapy and 2 with adalimumab combotherapy associated with azathioprine. In total, 63 (20.9%) patients were under biological therapy. The frequency of active TB disease among patients exposed to anti-TNF when compared to patients not exposed was 6.3% (4/63) and 1.7% (4/239), respectively, and the difference was significant (P = 0.047) between those groups. The median time between initiation of anti-TNF therapy and the diagnosis of TB was 19 months (range: 3.0–45.0). CONCLUSION(S): The frequency of latent TB in our center is comparable to the frequency described in IBD patients from endemic countries. It was observed a high frequency of active TB in IBD patients under anti-TNF therapy from a reference center in Brazil. ACKNOWLEDGMENT: Fellowship Program from University of the State of Bahia (PICIN UNEB).

Risk of incident Mycobacterium tuberculosis infection in patients with inflammatory bowel disease: a nationwide population-based study in South Korea.

The low incidence of Mycobacterium tuberculosis infection and lack of adequate controls have prevented researchers from estimating tuberculosis (TB) risk in inflammatory bowel disease (IBD) patients. To evaluate the risk of incident TB among IBD patients. Using the 2011-2013 data of the South Korean National Health Insurance (NHI) system, we calculated the incidence rates (IRs), standardised incidence ratio (SIR) and number needed to screen (NNS) for incident TB in IBD patients compared to the general population in terms of subtype, age, gender and IBD medications. The IR, SIR and NNS for TB in IBD patients were 223.9/100000 person-years, 2.64 (2.30-3.01) and 446.6 (392.8-517.6), respectively. The TB IR in Crohn's disease (CD) patients was significantly higher than that in ulcerative colitis (UC) patients (340.1/100000 person-years vs. 165.5/100000 person-years, respectively; P<0.001). The SIR and NNS for TB among CD patients were 4.00 (3.59-4.45) and 604.2 (506.1-749.6), respectively; those among UC patients were 1.95 (1.66-2.27) and 294.0 (246.9-363.4). The TB IRs in IBD patients did not differ significantly by age or gender (Ptrend =0.505 and P=0.861, respectively). The TB IRs among IBDpatients prescribed 5-ASA, corticosteroids, immunomodulators and anti-TNF-α were 143.5, 208.5, 284.6 and 554.1 per 100000 person-years, respectively. Among IBD patients treated using anti-TNF-α, the TB IR was significantly higher than that among all IBD patients (P<0.001); the SIR and NNS for TB were 6.53 (5.99-7.09) and 180.5 (144.6-240.1) respectively. Clinicians should be aware of the increased risk of active tuberculosis in patients with IBD who are receiving anti-TNF-α therapy.

The risk of tuberculosis in Korean patients with inflammatory bowel disease receiving tumor necrosis factor-α blockers.

The aims of this study were to assess the risk of tuberculosis (TB) and the status of latent tuberculosis infection (LTBI) in Korean patients with inflammatory bowel disease (IBD) receiving tumor necrosis factor (TNF)-α blockers. We reviewed medical records of 525 Korean IBD patients (365 TNF-α blocker naïve and 160 TNF-α blocker exposed) between January 2001 and December 2013. The crude incidence of TB was significantly higher in IBD patients receiving TNF-α blockers compared to TNF-α-blocker-naïve patients (3.1% vs. 0.3%, P=0.011). The mean incidence of TB per 1,000 patient-years was 1.84 for the overall IBD population, 4.89 for TNF-α blocker users, and 0.45 for TNF-α-blocker-naïve patients. The adjusted risk ratio of TB in IBD patients receiving TNF-α blocker was 11.7 (95% confidence interval, 1.36-101.3). Pulmonary TB was prevalent in patients treated with TNF-α blockers (80.0%, 4/5). LTBI was diagnosed in 17 (10.6%) patients, and none of the 17 LTBI patients experienced reactivation of TB during treatment with TNF-α blockers. Treatment with TNF-α blockers significantly increased the risk of TB in IBD patients in Korea. De novo pulmonary TB infection was more prevalent than reactivation of LTBI, suggesting an urgent need for specific recommendations regarding TB monitoring during TNF-α blocker therapy.

Tuberculosis in an inflammatory bowel disease cohort from South Africa

Potent immunosuppressive therapy is standard treatment for inflammatory bowel disease (IBD) but carries a risk of reactivating latent tuberculosis (TB). No data exist on the burden of TB in South African patients with IBD. To evaluate the burden of TB in IBD patients attending a large tertiary IBD clinic. A retrospective analysis was performed on data pertaining to patients attending the Groote Schuur Hospital IBD clinic. Data were extracted from an existing IBD database, patient notes, the National Health Laboratory Services database and chest X-ray analysis. Of 614 patients, 72 (11.7%) were diagnosed with TB; 40 (55.6%) developed TB prior to the diagnosis of IBD. On regression analysis, coloured IBD patients were at increased risk for TB development (p=0.004, odds ratio (OR) 3.57, 95% confidence interval (CI) 1.49 - 8.56), as were patients with extensive Crohn's disease (CD) compared with those with less extensive disease (p=0.001,OR 2.84, 95% CI 1.27 - 6.33). No other risk factors, including the use of immunosuppressive agents, were identified for the development of TB. Of over 600 patients, 12% had TB either before or after IBD diagnosis. The high rate of previous TB and positive association with ethnicity probably reflects the high burden of TB in a socio-economically disadvantaged community. We recommend that IBD patients should be screened actively and monitored for TB when immunosuppressive medications are used.

Serious infections in patients with inflammatory bowel disease receiving anti‐tumor‐necrosis‐factor‐alpha therapy: An Australian and New Zealand experience

Anti-tumor-necrosis-factor-alpha (anti-TNF-α) medications are effective in inflammatory bowel disease (IBD), but have an increased risk of tuberculosis (TB) and serious infections. The aim of this study was to examine the Australian/New Zealand experience of serious infections and TB in IBD patients receiving anti-TNF-α therapy from 1999-2009. Serious infections, defined as 'requiring hospital admission' and TB cases in patients receiving, or within 3 months following, anti-TNF-α therapy were analyzed across Australia and New Zealand. Patient demographics, IBD medications, duration of anti-TNF-α therapy, and infection details were collected. A total of 5562 IBD patients were managed across the centers. Of these, 489 (16.8%) Crohn's disease and 137 (5.2%) ulcerative colitis patients received anti-TNF-α therapy. There were three cases of latent TB that received prophylaxis prior to anti-TNF-α therapy. No cases of active TB were reported. Fourteen (2.2%) serious infections occurred. Seven occurred in patients receiving anti-TNF-α therapy for less than 6 months, including two cases of primary Varicella zoster (VZV), two cases of Pneumocystis jiroveci pneumonia, two cases of Staphylococcus aureus bacteremia, and one severe flu-like illness. Six patients were taking additional immunosuppressive medications. The other seven infections occurred after 6 months (mean 32.6 ± 24.3 months) and included one case of primary VZV, one flu-like illness, and five bacterial infections. All infections resolved with treatment. TB is a very rare complication of anti-TNF-α therapy in Australia and New Zealand. Serious infections are uncommon but early opportunistic infections with Pneumocystis jiroveci pneumonia suggest a need for vigilance in patients on multiple immunosuppressive medications. VZV vaccination prior to immunosuppressive therapy should be considered in VZV-naïve patients.