Research Communication: Risk of Tuberculosis With Advanced Therapies in 20,705 Patients With Inflammatory Bowel Diseases in Low Incidence Regions-A U.S. Claims-Based Study.

To describe the incidence rates of inflammatory bowel disease (IBD) and tuberculosis (TB) in Korean patients with ankylosing spondylitis receiving biologics. Data from a Korean claims database between 2010 and 2021 was used to calculate crude incidence rates of TB and IBD using number of events and total patient-years (PYs). Overall, 43 643 and 43 396 patients were included in TB and IBD cohorts, respectively. Exposure-adjusted incidence rates (EAIRs) of TB for non-exposure, TNF inhibitors (TNFis), and IL-17 inhibitors (IL-17is) were 0.14, 0.25 and 0.12 and of IBD were 0.18, 0.19 and 0.44 per 100 PYs, respectively. Incidence rates during biologic DMARD (bDMARD) non-exposure, adalimumab, etanercept, golimumab, infliximab, secukinumab and ixekizumab exposures for TB were 13.96, 27.79, 14.28, 21.19, 33.62, 12.74 and 0.00 and for IBD were 18.29, 19.98, 22.41, 18.85, 15.73, 44.99 and 0.00 per 10 000 PYs, respectively. Compared with bDMARD non-exposure, adalimumab, golimumab and infliximab exposures were associated with a significantly higher risk of TB. Etanercept and secukinumab exposure showed no significant increase in risk of TB. Compared with bDMARD non-exposure, exposure to biologics did not show a significant difference in risk of IBD. EAIRs of TB and IBD with use of IL-17is in patients with AS were within anticipated low range. IL-17is had numerically lower incidence of TB, and numerically higher incidence of IBD compared with TNFis. Notably, secukinumab showed no increased risk of TB compared with bDMARD non-exposure. Neither TNFis nor IL-17is showed increased risk of IBD compared with bDMARD non-exposure.

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The aim of this study was to assess the risk of active tuberculosis (TB) in patients with immune-mediated inflammatory diseases treated with biologics and tofacitinib in randomized controlled trials (RCTs) and long-term extension (LTE) studies. A systematic review of the English-language literature by was performed by searching the Medline, Embase, Cochrane and Web of Knowledge databases. The search strategy focused on synonyms of diseases, biologics and tofacitinib. Data from RCTs were combined to assess the rate of TB using a random effects model. The incidence rate (IR) of TB and its association with disease, location and treatment were assessed in LTE studies. The search captured 11 130 articles and abstracts. One-hundred RCTs (75 000 patients) and 63 LTE studies (80 774.45 patient-years) met the inclusion criteria. There were 31 TB cases with TNF inhibitors, 1 with abatacept and none with rituximab, tocilizumab, ustekinumab or tofacitinib. The odds ratio for TNF inhibitors was 1.92 (95% CI 0.91, 4.03, P = 0.085). In LTE studies, the IR of TB was >40/100 000 with tofacitinib and all biologics except rituximab. IR was higher in RA patients with anti-TNF monoclonal antibodies [307.71 (95% CI 184.79, 454.93)] than in those with rituximab [20.0 (95% CI 0.10, 60)] and etanercept [67.58 (95% CI 12.1, 163.94)] or AS, PsA and psoriasis with etanercept [60.01 (95% CI 3.6, 184.79)]. The IR of TB was higher in high-background TB areas. RCTs are not sensitive enough to assess the risk of reactivation of latent TB infection (LTBI). Disease, treatment and background TB rate are associated with different frequencies of active TB. The benefit/risk balance of preventing reactivation of LTBI in different backgrounds should be considered in clinical practice.

Mo1727 High Incidence of TB in Large Hospital Database-Based Studies of IBD Patients in the Era of Biologics

BACKGROUND: Despite the decline in the incidence of Tuberculosis (TB) worldwide, this disease still causes high rates of morbimortality. It is estimated that TB caused 1.3 million deaths worldwide in 2017. Brazil is an endemic country and it counts nearly 70,000 new cases of TB per year (1). Whether the risk of TB infection in Inflammatory Bowel Disease (IBD) patients is related to immunosuppressants or to the disease itself is controversial. This study aimed to evaluate the incidence of active TB in patients with IBD, and its relationship with immunosuppressive treatment in a tertiary referral center. METHODS: Patients with active TB were identified among 1040 IBD patients in a regular follow up at Hospital das Clínicas, São Paulo, Brazil, from 2010 to 2017. Data regarding disease phenotype, IBD treatment at the time of TB diagnosis and the previous status of TB screening was retrospectively collected from electronic medical records. The diagnosis of active TB was based on symptoms, tuberculin skin test (TST), sample cultures, images, and endoscopic exams. RESULTS: Twenty-three patients with active TB were identified (mean age at TB diagnosis 49 [28–69]; 13/23 [56.5%] female). The person-time incidence rate of active TB was 2.21 cases/100 inhabitants/year in our IBD population. The relative risk of active TB was increased (RR 6.6) compared to general Brazilian population. Fifteen patients (65.2%) had Crohn’s Disease (7 perianal; 4 stricturing; 4 non-penetrating non-stricturing) and eight (34.7%) had Ulcerative Colitis (7 extensive disease). Regarding IBD treatment, 13/23 (56.5%) patients were under anti-TNF drugs (9 Infliximab; 4 Adalimumab), six of them (46.1%) in monotherapy and seven (53.8%) under combotherapy with thiopurines. Five patients (21.7%), were under AZA monotherapy and one was under steroids. Regarding the interval between anti-TNF use and TB diagnosis, just one case was diagnosed in the first 6 months of treatment. Most patients (14/19; 73.6%) developed active TB after 24 months of exposition to immunosuppressant medications; two (2/19; 10.5%) between 12–24 months of exposure and three (3/19; 15.7%) between 6–12 months. All four of the patients (4/23; 17.4%) that were not under immunosuppressant drugs were smokers, one of them was also an alcoholic and another one treated active TB seven years before the reinfection. The most common TB site was pulmonary (16/23, 69.5%) and no deaths resulted from active TB. One case of TB occurred three years after isoniazid chemoprophylaxis for latent TB in a patient under combotherapy (anti-TNF and AZA). CONCLUSION(S): Our patients presented an incidence of TB higher than the general population in Brazil. Immunosuppressive drugs seem to be a major causal factor, especially anti-TNF. Most cases occurred after the first six months of treatment suggesting a new infection. This study reinforced the importance of an accurate screening for TB at IBD diagnosis and prior to initiation of immunosuppressive therapy. Appropriate follow-up is required in immunosuppressed patients living in endemic areas for TB.

BackgroundAnti-tumor necrosis factor (TNF) treatment for inflammatory bowel disease (IBD) increases the risk of tuberculosis (TB) infection. In the present study, we analyzed the clinical characteristics and risks of TB in Korean patients with IBD who received anti-TNF treatment.MethodsThe study included patients with IBD who were treated using anti-TNF agents between January 2001 and June 2018 at the Asan Medical Center. Overall, 1434 patients with ulcerative colitis or Crohn’s disease were enrolled. We calculated the incidence of active TB infection after anti-TNF treatment and compared the clinical characteristics of the TB group with those of the non-TB group.ResultsTwenty-one patients (1.46%) developed active TB infection, and the incidence rate of active TB was 366.73 per 100,000 person-years. In total, 198 patients (14.9%) were positive for latent tuberculosis infection (LTBI), of whom only eight (4%) did not complete LTBI treatment. The age at which the anti-TNF therapy was started was significantly higher in the TB group than in the non-TB group (HR 1.041, 95% CI 1.014–1.069, p = 0.002), and as age increased, so did the incidence rate of active TB infection (linearity p < 0.001). There was no significant difference in the incidence rate of LTBI between the TB and non-TB groups (HR 0.896, 95% CI 0.262–3.066, p = 0.862).ConclusionsIn patients with IBD, the incidence rate of TB increased with age at anti-TNF therapy initiation. Active treatment of LTBI may lower the incidence of TB in patients with IBD who are to undergo anti-TNF therapy.

Mo1731 Prevalence and Risk Factors for Vitamin D Deficiency in Ulcerative Colitis

Mo1728 Increased Rate of Non Melanoma Skin Cancer Detection With Screening Skin Exam in Inflammatory Bowel Disease: Is it Time to Recommend Routine Dermatology Care?

Advanced therapies in inflammatory bowel disease: Special considerations.

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.

Background Inflammatory bowel disease (IBD) is a state of excess inflammatory cytokines, including tumor necrosis α (TNF). Studies in human and animal models showed that TNF has an important role in pathophysiology of insulin resistance (1). While there is some evidence of a link between IBD and diabetes mellitus (DM) and that anti-TNF therapy is associated with better glucose levels in patients with IBD and DM (2), the potential for prevention of onset or impact of other advanced therapies has not been described. Methods We used the TriNetX global federated network to identify patients with IBD ≥18 years diagnosed with IBD between 2019 and 2024, and who were treated with advanced therapy within 2 years of that diagnosis. Patients who were diagnosed with DM prior or within 3 months of IBD diagnosis or treatment were excluded. The primary endpoint was a diagnosis of DM or a HgbA1C&amp;gt;6.5%. Patients were divided into two different cohorts: 1) patients treated with anti-TNF, and 2) patients treated with vedolizumab, IL23 inhibitors or JAK inhibitors, and never with anti-TNF. Patients were compared using a 1:1 propensity matching by race, gender, age, sociodemographic comorbidities, BMI, hypertension, long term use of steroids, ischemic heart disease, IBD subtype and past total or partial colectomy. A diagnosis of psoriasis was used as positive control outcome, and a diagnosis of upper respiratory tract infections (URTI) was used as negative control outcome. Results 43,372 patients with a new diagnosis of IBD were identified: 30,583 treated with anti TNF and 12,789 treated with other advanced therapies. Following propensity scored matching, 12,762 patients were in each balanced cohort. After a follow up of 3 years, patients treated with anti TNF had a 72.5% lower risk for subsequent diabetes (0.3% vs. 1.04% HR 0.275, 95% CI 0.174 -0.437, p&amp;lt;0.001), a higher risk of psoriasis (HR 1.35, 95% CI 1.074 - 1.694, p&amp;lt;0.001) but no significant difference of URTI (Figure 1). Conclusion Patients with IBD treated with anti-TNF have a significantly lower risk of developing diabetes compared to patients treated with other advanced therapies. The mechanisms and protective effect of anti-TNF therapy warrants further investigation.

BACKGROUND Data on patients with inflammatory bowel disease (IBD) undergoing solid organ transplantation (SOT) are scarce. Most studies have focused on liver transplantation (LT) in IBD patients with primary sclerosing cholangitis (PSC), while IBD-related outcomes in other organ transplants are less well-described. In this study, we sought to characterize the population of patients with IBD undergoing SOT and describe both IBD and SOT outcomes. METHODS A single-centered, retrospective cohort study of patients with IBD who had an SOT from 2010 through 2022. Electronic records were reviewed for demographics, IBD, and transplantation history. IBD clinical activity (based on provider assessment), endoscopic activity, and medication use were assessed at time of SOT, one-year post-transplant, and at most recent follow-up. SOT outcomes evaluated included post-transplant medication use, rejection, and re-transplantation. RESULTS 69 patients with IBD underwent SOT (Table 1). The most common SOT was LT (n= 43), followed by kidney (KT)(n= 17), heart (n= 7), and liver/kidney (n= 2). The most common indication for LT was PSC (81%). The most common indications for KT were IgA nephropathy and interstitial nephritis (both n= 3). Nonischemic cardiomyopathy was the most common indication for heart transplant (71%). The mean follow-up time was 5.3 years post-SOT. At the time of SOT, 96% of patients were in clinical IBD remission. 15 patients had previously undergone colectomy. At the time of SOT, 36% patients were on no IBD therapy, 23% were on 5-ASA, 19% on immunomodulators, and 28% on advanced therapy (AT). At 1-year post-SOT, 91% were in clinical remission (Table 2) however 17% of patients who underwent endoscopic evaluation had endoscopic inflammation. There was a non-significant trend towards more IBD activity on endoscopy at 1-year post-SOT in patients on no IBD medications post-SOT (44% v 31%, p=0.5). 67% patients were on no specific IBD therapy 1-year post-SOT (SOT immunosuppression only). At 1-year post-SOT, only 12% were on AT; 1 patient was started post-SOT. The most common AT was vedolizumab (n= 7) followed by infliximab (n= 6). At last follow-up, 22% patients were on AT. Post-SOT, 29% of patients had an episode of acute rejection within 1 year, and 10% required re-transplantation of organ within the follow-up period. There was no statistical association between IBD status at the time of SOT or IBD advanced therapy use on transplant outcomes (data not shown). 29% of the patients were deceased at the end of our follow-up period with an average time to death of 4.95 years post-SOT. CONCLUSION In our cohort, most IBD patients undergoing SOT are in clinical remission at the time of SOT and do not require specific IBD therapy post-transplant. Despite the use of immunosuppression for SOT, some IBD patients still require AT for control of their disease. Table 1. Patient Characteristics Table 2. Pre- and Post-Transplant IBD Related Outcomes

While there are multiple safe and effective agents for COVID-19 treatment, their impact in inflammatory bowel disease (IBD) remains uncertain. Our objective was to assess the effects of these therapies on both IBD and COVID outcomes. A single-center retrospective study of adult patients with IBD who contracted COVID-19 between 12/2020 and 11/2022 was performed. Patients were stratified by COVID-19 treatment (antivirals and/or intravenous antibodies) vs no therapy. The primary outcome was the development of severe COVID-19 infection, defined by need for supplemental oxygen, corticosteroids and/or antibiotics, or hospitalization. Secondary outcomes included rates of withholding advanced IBD therapy (defined as biologic agents or small molecules) and of post-COVID-19 IBD flare. Of 127 patients with COVID-19 infection, 70% were on advanced therapies, 35% received COVID-19 treatment, and 15% developed severe COVID-19. Those treated for COVID-19 were more likely to be on corticosteroids [odds ratio (OR) 4.61, 95% confidence interval (CI) 1.72-12.39, p = 0.002] or advanced IBD therapies (OR 2.78, 95% CI 1.04-7.43, p = 0.041). After adjusting for age, race, sex, corticosteroid use, obesity, COVID-19 vaccination status, and severe COVID-19 infection, those treated for COVID-19 were more likely to have IBD therapy held (OR 6.95, 95% CI 1.72-28.15, p = 0.007). There was no significant difference in rates of post-COVID-19 IBD flares or severe COVID-19 infection. There were no COVID-related deaths. Patients with IBD on advanced therapies were frequently treated for acute COVID-19. Although COVID-19 treatment was associated with temporary withholding of IBD therapy, it did not result in increased IBD flares.

Background Data suggest limited use of advanced therapies (AT) in inflammatory bowel disease (IBD) despite the accumulating data for the benefits of early, broader AT use.1-3 We evaluated barriers to AT use in IBD using a multimodal approach. Methods Market research was conducted June-November 2023. Quantitative survey on prescribing trends amongst gastroenterologists (GEs) prescribing ATs was conducted to capture AT initiation drivers in Germany, Italy, UK and US; questions for this survey were identified in qualitative interviews. GEs cycling an average of 0-1 and ≥2 conventional therapies (CTs) before initiating AT were classified as low and high cyclers, respectively. The COM-B (Capability, Opportunity, Motivation and Behaviour) model was used for behavioural analysis.4 Results Qualitative analysis covered responses from 62 participants (28 patients [pts], 24 GEs, 7 nurses, 3 pt organisation representatives), and quantitative analysis – from 142 GEs (Germany, 30; Italy, 30; UK, 30; US, 52) currently prescribing ATs, with 559 pt report forms (ulcerative colitis [UC], 280; Crohn’s disease [CD], 279) collected. CT cycling was more prevalent in UC vs CD; AT treatment was less likely in pts with UC vs CD (Figure). Differences among GEs by geography were only partially explained by cost containment in highly regulated markets (eg, Italy, UK). High cycling variations were linked to behavioural and belief-driven factors as illustrated by the notable use (7-20%) of 5-aminosalicylates in CD despite the lack of clinical guideline support. In behavioural analysis, AT initiation barriers included a lack of awareness of AT value and prescribing approach of exhausting all CT options before initiating AT. Low vs high cyclers placed higher importance on patient preference (UC, +16%; CD, +19%) and peer recommendations (UC, +13%; CD, +20%). In UC, the belief of exhausting all CT options before initiating AT was more important for high vs low cyclers (+9%). Qualitative research showed that the lack of clear guidelines disproportionately impacted high cyclers as they had reduced academic interest and limited capacity as contributors. Physician-relevant AT initiation drivers were the perceived CT risks and the growing recognition of the AT clinical value and long-term impact on the quality of life. Pt-relevant drivers included improved AT awareness and the ability and confidence for pts to self-advocate. Conclusion Cost containment and guideline variations could partially explain the observed geographic variations in AT use. Within any given country, clinical beliefs play a determining role. In Europe, a tangible increase in AT vs CT share could be achieved by encouraging GEs to initiate AT in pts with poor prognostic factors as per guideline suggestions.

Background No tools exist to individualize treatment selection in Inflammatory bowel disease (IBD) to optimize outcomes. We prospectively recruited patients prior to initiation of molecularly targeted (advanced) therapy (MTT) to identify predictive biomarkers of response and define pathways impacted by successful treatment. Methods Serum was collected before initiation of treatment in all patients, and at visit 1 (V1~16 wks) for a subset of patients. Serum samples were analyzed for &amp;gt;140 protein biomarkers (OLINK) and &amp;gt;1200 lipid metabolites. Whole exome sequencing and GWAS data was generated for all participants. Initial data outline proteomic data. Results Of the first 166 IBD patients analyzed, therapies initiated included TNF antagonists (n=85), ustekinumab (n=43), vedolizumab (n=28) and janus kinase inhibitors (n=10). Bio-naïve (n=96) and patients using baseline corticosteroids (n=77) were included. Sixty-three patients achieved remission. In TNF-antagonist initiations, serum TNF concentrations increased between baseline and V1 (p=4E-3), while it decreased for other MTTs (p=0.07). In bio-naïve patients, serum TNF concentration had a strong correlation with CXCL10 (r=0.58, P=3E-10). From the Principal Component Analysis of analytes correlated to TNF in bio-naïve patients, we built a proxy for the level of active TNF. At baseline, compared to TNF antagonist naïve patients, significantly higher serum TNF concentrations existed in patients with prior TNF-antagonist exposure &amp;gt;1-month post-cessation and a markedly high TNF concentration with cessation &amp;lt;1 month prior to baseline (p&amp;lt; 2E-16). In patients with prior TNF-antagonist exposure, serum TNF concentrations did not correlate with other cytokines (incl. CXCL10). In these patients, elevated serum TNF were found at V1, suggesting accumulation of inactive (complexed) TNF with treatment. A similar pattern was observed for IL-12 after ustekinumab treatment (elevated serum IL-12 with recent ustekinumab (p= 8E-13), large increase in IL-12 after ustekinumab (p=9E-5)). Reduced IL-12 concentrations existed in current corticosteroid users, compared to previous users and those who never used (p=4E-8). In baseline samples in bio-naive patients prior to therapy initiation, serum concentrations of six analytes provided a discriminant model of corticosteroid use, whith an area under (AUC) the receiver operation characteristic (ROC) curve showed excellent discrimination (AUC=0.91). Conclusion These data uniquely characterize proteomic data in patients with various advanced therapies and will enable development of predictive panels. Unique availability of multiple therapies linked to longitudinal proteomic data may allow personalized panels for treatment selection.