Use Of Thiopurines Research Articles

Long-term prognosis of ulcerative colitis and its temporal changes between 1986 and 2015 in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea

ObjectiveNo population-based study has evaluated the natural course of UC over three decades in non-Caucasians. We aimed to assess the long-term natural course of Korean patients with UC in a...

Aspects of inflammatory bowel disease during the COVID-19 pandemic and general considerations

So far, available evidence suggests that patients with inflammatory bowel disease (IBD) are not at greater risk for developing COVID-19 infection. In regard to patients with IBD remission: 5-aminosalycylates (5-ASAs) do not increase the risk for infection and should be continued. There is no need to suspend them or lower the dose. Immunomodulating drugs, such as thiopurines and methotrexate, should be continued, without modifying doses (even in patients with positive SARS-CoV-2 infection). No type of biologic therapy should be suspended, unless there are signs of COVID-19. Regarding patients with IBD activity: the oral and/or topical 5-ASA dose should be optimized in cases of disease relapse. Budesonide MMX should be considered in cases of mild-to-moderate activity, to avoid systemic steroid use. Systemic steroids should be avoided whenever possible because doses above 20 mg per day have an immunosuppressive effect, which could increase susceptibility to any type of infection, including COVID-19. The combined use of thiopurines with steroids and/or tumor necrosis factor (TNF) monoclonal antibodies should also be avoided because those combinations can increase the risk for infections, including COVID-19. Finally, biologic treatment with anti-TNF-alpha agents or any other mechanism of action, such as anti-integrins or anti-interleukins, should be suspended if patients become infected with SARS-CoV-2. The drugs can be restarted once the infectious process is resolved.

Adherence of Infusible Biologics During the Time of COVID-19 Among Patients With Inflammatory Bowel Disease: A Nationwide Veterans Affairs Cohort Study

Adherence of Infusible Biologics During the Time of COVID-19 Among Patients With Inflammatory Bowel Disease: A Nationwide Veterans Affairs Cohort Study

Safety of Thiopurine Use in Paediatric Gastrointestinal Disease.

Thiopurines, alone or in combination with other agents, have a pivotal role in the treatment of specific gastrointestinal and hepatological disorders. In inflammatory bowel disease and autoimmune hepatitis thiopurines have proven their value as steroid sparing agents for the maintenance of remission and may be considered for preventing postoperative Crohn disease recurrence where there is moderate risk of this occurring. Their use with infliximab therapy reduces antibody formation and increases biologic drug levels. The routine clinical use of thiopurines has, however, been questioned due to a number of potential adverse effects. The aim of this article is to provide information regarding the use, and in particular, safety of these agents in clinical practice in the light of such potentially severe, albeit rare, effects.

NUDT15 gene variants and thiopurine-induced leukopenia in patients with inflammatory bowel disease.

Thiopurine has been used to maintain remission and to reduce antidrug antibody formation in monoclonal antibody therapy in patients with inflammatory bowel disease (IBD). The use of thiopurine is limited by side effects such as leukopenia. Thiopurine S-methyltransferase (TPMT) variants are associated with thiopurine-induced leukopenia in Westerners, but the frequency of the risk alleles is low in Asians. Recently, a variant in the nudix hydrolase 15 (NUDT15) gene (R139C, c.415C > T) was reported to be associated with early severe leukopenia in Asians. NUDT15 is an enzyme that converts 6-thio-(deoxy)guanosine triphosphate (6-T(d)GTP) to 6-thio-(deoxy)guanosine monophosphate (6-T(d)GMTP). The R139C variant impairs the stability of the protein and increases incorporation of 6-TGTP and 6-TdGTP into RNA and DNA, respectively, resulting in leukopenia. The frequency of C/C, C/T, and T/T are approximately 80%, 20%, and 1%, respectively in East Asians. Early leukopenia occurred in less than 3% of patients with C/C and in around 20% of those with C/T, whereas it occurred in almost all patients with T/T. Patients homozygous for this variant also develop severe hair loss. The measurement of NUDT15 R139C can increase the safety of thiopurine dramatically and is a successful example of personalized medicine in the field of IBD.

Impact of Anti-Tumor Necrosis Factor and Thiopurine Medications on the Development of COVID-19 in Patients With Inflammatory Bowel Disease: A Nationwide Veterans Administration Cohort Study

Impact of Anti-Tumor Necrosis Factor and Thiopurine Medications on the Development of COVID-19 in Patients With Inflammatory Bowel Disease: A Nationwide Veterans Administration Cohort Study

Gastroenterologists' preference and risk perception on the use of immunomodulators and biological therapies in elderly patients with ulcerative colitis: an international survey.

Comorbidities, polypharmacy, malignancies, and infections complicate management of elderly patients with inflammatory bowel diseases (IBD). This study assessed gastroenterologists' preference in the prescription of medications or surgery to elderly patients with IBD, and the factors associated with their choices. An international case-based survey was conducted that presented three cases of steroid-dependent ulcerative colitis assessing young-age versus elderly-age patients, with and without comorbidity. Physician characteristics and practice demographics were collected. Factors associated with selection of different choices of therapy were determined by logistic regression analysis. A total of 424 respondents from 41 countries were included. Vedolizumab (53.2%) and thiopurines (19.4%) were the top treatment preferences for moderate-to-severe ulcerative colitis (P < 0.0001). Comorbidity and older age were independently associated with more frequent use of vedolizumab (P < 0.0001), and less frequent use of immunomodulators and anti-tumour necrosis factor (TNF; P < 0.0001). Comorbidity was the only independent predictor for selecting colectomy (P < 0.0001). A history of lymphoma (94%) and opportunistic infection (78.3%) were the most frequent conditions precluding the use of thiopurine and anti-TNF in elderly patients with IBD. Only 6.1% of respondents considered patient age a limit for vedolizumab, while 37.9% considered age as a limiting factor in prescribing thiopurines (P < 0.001). Geographical heterogeneity was identified with significantly more physicians from Oceania and North America favouring the use of vedolizumab. Vedolizumab was the preferred first-line agent in the treatment of elderly patients with IBD with steroid-dependent moderate-to-severe ulcerative colitis. Older age and presence of comorbidity influenced the selection of medication. Comorbidity was the main predictor of colectomy. Geographical heterogeneity in prescribing habits may relate to medication reimbursement in individual countries.

Repeated Occurrences of Basal Cell Cancer in Patients With Inflammatory Bowel Disease Treated With Immunosuppressive Medications

There are limited data on repeated basal cell cancer (BCC) occurrences among patients with inflammatory bowel disease (IBD), especially the impact of continuing immunosuppressive medications. We conducted a retrospective cohort study of 54,919 patients with IBD followed in the Veterans Affairs Healthcare System. We identified patients who had an incident BCC after their IBD diagnosis. We defined patients' exposure based on their IBD medications use as follows: (i) only aminosalicylate (5-ASA) use, (ii) only active thiopurine (TP) use, (iii) past TP use (discontinued >6 months ago) and no antitumor necrosis factor (TNF) use, (iv) anti-TNF use after previous TP use, (v) only anti-TNF use, and (vi) active anti-TNF and TP use. The outcome of interest was the repeated occurrence of BCC. Adjusted and unadjusted hazard ratios with 95% confidence intervals were used to estimate the risk of repeated BCC occurrence. A total of 518 patients developed BCC after their IBD diagnosis. The numbers of repeated BCC occurrences per 100 person-years were 12.8 (5-ASA use only), 34.5 (active TP use), 19.3 (past TP use and no anti-TNF use), 25.4 (anti-TNF use after previous TP use), 17.8 (only anti-TNF use), and 22.4 (active anti-TNF and TP use). Compared with 5-ASA use alone, only active TP use was associated with an increased risk for repeated BCC occurrence (adjusted hazard ratio 1.65, 95% confidence interval 1.24-2.19; P = 0.0005). However, the increased risk was no longer present for other exposure categories. Among IBD patients who developed an incident BCC while taking a TP and continued it, there was an increased risk of repeated BCC occurrences.

Increased incidence of systemic serious viral infections in patients with inflammatory bowel disease associates with active disease and use of thiopurines.

The magnitude and drivers of the risk of serious viral infections in Inflammatory Bowel diseases (IBD) are unclear. The objective of this study was to assess the incidence and risk factors for systemic serious viral infections in IBD patients. Using MICISTA, a database detailing prospective characteristics and complications of IBD, we identified patients that were followed for IBD in 2005-2014 outside the context of organ transplantation, HIV infection or chronic viral hepatitis. We estimated incidences of systemic serious viral infections, defined by the need for hospitalization or permanent organ damage. Standardized incidence ratios (SIRs) were calculated using the French hospital database. We performed a case-control study nested in MICISTA for assessing the role of exposure to IBD drugs and IBD clinical activity in the risk of developing infection. We identified 31 patients with serious viral infections among 2645 patients followed for 15,383 person-years. We observed 13 cases of cytomegalovirus, 10 Epstein-Barr virus, 5 varicella zoster virus and 3 herpes simplex virus infections. No deaths occurred. The incidence rate of infections in patients with IBD was 2.02/1000 person-years, and the SIR was 3.09 (95% confidence interval (CI), 1.98-4.20; p = 0.0002) in the study population. By multivariate analysis, increased risk of infection was associated with exposure to thiopurines (odds ratio (OR), 3.48; 95% CI, 1.36-8.90; p = 0.009), and clinically active IBD at onset of infection (OR, 3.35; 95% CI, 1.23-9.23; p = 0.02). The incidence of systemic serious viral infections in patients with IBD is tripled compared to general population. Clinically active IBD and exposure to thiopurines are the main drivers of the risk.

Concordance between tuberculin skin test and interferon-gamma release assay for latent tuberculosis screening in inflammatory bowel disease.

Background/AimsLatent tuberculosis screening is mandatory prior to initiating anti-tumor necrosis factor (anti-TNF) medications. Guidelines recommend interferon-gamma release assays (IGRA) as first line screening method for the general population. Studies provided conflicting evidence on IGRA and tuberculin skin test (TST) performance in inflammatory bowel disease (IBD) patients. We assessed test concordance and the effects of immunosuppression on their performance in IBD patients.MethodsWe searched MEDLINE, Embase and Cochrane databases (2011–2018) for studies testing TST and IGRA in IBD. Primary outcome was TST and IGRA concordance. Secondary outcomes were effects of immunosuppressive therapy on performance. Immunosuppression defined as either steroids, thiopurine, methotrexate or cyclosporine use. We used the pooled random effects model to adjust for heterogeneity analyzed using (I2–Q statistics). We compared the fixed model to exclude smaller study effects.ResultsSixteen studies (2,488 patients) were included. Pooled TST and IGRA concordance was 85% (95% confidence interval [CI], 81%–88%; P=0.01). Effects of immunosuppression were reported in 8 studies (814 patients). The odds ratio of testing positive by IGRA decreased to 0.57 if immunosuppressed (95% CI, 0.31–1.03; P=0.06). The odds ratio of testing positive by TST if immunosuppressed was 1.14 (95% CI, 0.61–2.12; P=0.69). The fixed model yielded similar results, however the negative effect of immunosuppression on IGRA reached statistical significance (P=0.01).ConclusionsWhile concordance was 85% between TST and IGRA, the performance of IGRA seems to be negatively affected by immunosuppression. Given the importance of detecting latent tuberculosis prior to anti-TNF initiation, further randomized controlled trials comparing the performance of TST and IGRA in IBD patients are needed.

Tacrolimus induces short-term but not long-term clinical response in inflammatory bowel disease.

Tacrolimus is a calcineurin inhibitor commonly used for prophylaxis of rejection in renal and liver transplantation. There are limited but favourable data regarding its possible use in patients with inflammatory bowel disease (IBD). To evaluate the efficacy and safety of tacrolimus in patients with IBD in clinical practice. We performed a retrospective, multicentre study in 22 centres in Spain. All adult patients who received oral tacrolimus for luminal or perianal IBD were included. Clinical response was assessed by Harvey-Bradshaw index and partial Mayo score after 3months. Perianal disease was evaluated by fistula drainage assessment. One hundred and forty-three patients were included (mean age 38years; 51% male; median disease duration 110months). In ulcerative colitis (UC) (n=58), the partial Mayo score decreased after 3months from median 6 to 3 (P=0.0001), whereas in Crohn's disease (CD) (n=85), the Harvey-Bradshaw index decreased after 3months from median 9 to 7 (P=0.011). In CD patients, blood tacrolimus concentrations during induction (>10ng/mL vs <10ng/mL; odds ratio 0.23, 95% CI 0.05-0.87) and the concomitant use of thiopurines (odds ratio 0.18, 95% CI 0.04-0.81) were associated with lower clinical disease activity at 3months. Of 62 patients with perianal disease, complete closure was observed in 8% (n=5) of patients with perianal fistulas, with 34% (n=21) showing partial response. Treatment was maintained for a median of 6months (IQR, 2-16). After a median clinical follow-up of 24months (IQR, 15-57), the rate of treatment-related adverse events was 34%, correlating with blood drug concentrations (P=0.021). Finally, 120 patients (84%) discontinued tacrolimus, usually due to absence or loss of response. Three patients (2%) were subsequently diagnosed with cancer. The overall rate of surgery was 39%, with a 33% colectomy rate in UC. Tacrolimus shows a clinical benefit in both CD and UC after 3months of treatment, but its long-term effectiveness and frequent adverse events remain relevant issues in clinical practice.

Role of Thiopurines in Pediatric Inflammatory Bowel Diseases: A Real-Life Prospective Cohort Study.

Use of thiopurines for inflammatory bowel diseases (IBDs) is declining in some parts of the world. We aimed to explore outcomes of thiopurines and predictors of response in a real-world prospective cohort of children with dose optimization. Children with IBD treated with thiopurines without biologics were enrolled. Dosing was guided by thiopurine S-methyltransferase-activity at baseline and by clinical response and toxicity at 4 months; 1 year into the study, therapeutic drug monitoring at 4 months was also considered in the decision making. The primary outcome was steroid-free remission without treatment escalation by 12 months (SFR), using the intention-to-treat approach. A total of 129 children were included (74% Crohn disease [CD] and 26% ulcerative colitis [UC]). SFR was achieved in 37 (39%) CD and 13 (39%) UC patients, and SFR with normal erythrocyte sedimentation rate/C-reactive protein in 20 (21%) and 9 (27%), respectively. At 4 months, mean corpuscular volume/white blood cell ratio and Δ absolute neutrophil count weakly correlated with 6-thioguanine (r = 0.33, P = 0.02 and r = 0.32, P = 0.02, respectively). In CD, SFR was associated with 4-month median weighted Pediatric Crohn Disease Activity Index (2.5 [IQR 0-7.5] in responders vs 5 in nonresponders [0-12.5], P = 0.048) and Δabsolute neutrophil count (1.7 [IQR 0.7-4.1] vs 0.05 [-2.3-0.9]; P = 0.03). Mild drug-related adverse events were recorded in 30 children (22%), 3 required stopping the drug. In this real-life prospective cohort using dose optimization, thiopurines were safe and effective in 21% of CD and 27% of UC patients, including normalization of C-reactive protein and erythrocyte sedimentation rate. Thiopurines remain a viable option in the treatment algorithm of mild-moderate pediatric IBD, especially in girls whose risk for lymphoma is lower.

P150 Risk of hepatitis flare in patients with previous hepatitis B virus exposure amongst inflammatory bowel disease patients: results from a territory-wide Hong Kong IBD Registry study

Abstract Background Biological therapies, thiopurines and steroid are commonly used in the treatment of inflammatory bowel disease (IBD) and may cause hepatitis B virus (HBV) reactivation. However, their exact risk of hepatitis B flare in patients with previous HBV exposure is poorly defined. We aim to study the risk of hepatitis flare in IBD patients with previous HBV exposure. Methods Patients were identified from a territory-wide Hong Kong IBD Registry. IBD patients who were negative for HBsAg and received biological therapies or thiopurines or steroids from 1 January 2000 to 30 June 2019 were included. Patients who were positive for total antibody to hepatitis B core antigen (anti-HBc) and/or hepatitis B surface antigen (anti-HBs) were defined to have previous HBV exposure. Primary endpoint was development of hepatitis flare (alanine Aminotransferase [ALT) &amp;gt;80U/L). Results Total 369 patients fulfilled the inclusion criteria and were classified into three groups: anti-HBs positive only (n = 246); anti-HBs and anti-HBc positive (n = 78) and anti-HBc positive only (n = 45). Median follow-up duration was 60 months (Interquartile range: 32.7–60 months). Seventy-six IBD patients (20.6%) developed hepatitis flare. Cumulative incidence of hepatitis flare were 13.2%, 18.3% and 22% at 12 months, 36 months and 60 months respectively. Use of thiopurine [adjusted hazard ratio (aHR) 2.56; 95% Confidence Interval (CI) 1.54 – 4.26, p &amp;lt; 0.001]and ever exposure to steroid [aHR 2.73; 95% CI 1.30–5.72; p = 0.008] were risk factors for hepatitis flare after adjustment of baseline ALT level. The use of biological therapy was not associated with risk of hepatitis flare [aHR 1.79; 95% CI 0.79–3.99; p = 0.14]. Ever exposure to steroid was associated with increased risk of hepatitis flare irrespective of the peak dose (&amp;lt;20mg prednisolone daily, 20-40mg daily or &amp;gt;40mg daily) [aHR: 2.34–4.18]. Fifteen patients (4.1%) developed severe icteric hepatitis flare (ALT &amp;gt; 120U/L and bilirubin &amp;gt;38 mmol/L). Cumulative incidence of severe icteric hepatitis flare were 2.7%, 7.2% and 8.4% at 12 months, 36 months and 60 months respectively. Conclusion Amongst IBD patients with previous HBV exposure who were treated with biological therapy, thiopurines or steroid, 20.6% developed hepatitis flare. The use of thiopurine and ever exposure to steroid were risk factors for hepatitis flare. The use of biological therapy was not associated with risk of hepatitis flare.

P527 A review of adverse events associated with immunosuppressive treatments in inflammatory bowel disease patients

Abstract Background Medical therapies that suppress various pathways involved in inflammation comprise the mainstay of inflammatory bowel disease (IBD) treatment. Adverse events, including the development of serious infection and malignancy, have been associated with these therapies. This study evaluates the current evidence regarding serious adverse events associated with immunosuppressive agents in the IBD patient population. Methods A systematic search was conducted in September 2019 by combining three key research themes: inflammatory bowel disease, immunosuppression, and adverse events. For this systematic review, adverse events are defined as either the development or recurrence of malignancy or the development of serious infection necessitating hospital admission. Results There is a demonstrated association between thiopurine use and increased risk of both nonmelanoma skin cancer (NMSC) or lymphoma. The length of thiopurine exposure required to increase NMSC risk is, however, unclear. Of the papers reporting on exposure length and NMSC risk, the thiopurine exposure duration required to result in a statistically significant increase in NMSC risk varied from 6 months to 5 years. Among the studies retrieved, there is a lack of consensus on malignancy risk associated with the use of anti-TNF agents. From 5 studies on malignancy risk associated with the use of anti-TNF agents, one concluded that malignancy risk is increased while three concluded that risk is unchanged from baseline. The fifth study is inconclusive on any possible association. Confounding by past or concurrent thiopurine exposure remains an issue. There is a clear association between combination therapy with both thiopurines and anti-TNF agents and increased malignancy risk when compared with exposure to either thiopurine or anti-TNF therapy alone. Anti-integrin agents were not found to be associated with an increase in adverse effects when compared with placebo, while nil studies on ustekinumab were retrieved. Individual studies on infection risk do not consistently stratify infections according to severity, limiting any analysis. Conclusion An established association between thiopurine use and increased risk of both lymphoma or NMSC exists. However, the duration of thiopurine exposure necessary to increase NMSC risk is uncertain. There is a lack of consensus on whether anti-TNF agents increase malignancy risk due to confounding from past or concurrent thiopurine exposure. Combination therapy increases malignancy risk when compared with exposure to either thiopurine or anti-TNF therapy alone. Limited studies on the newer biologic therapies were retrieved. Finally, evidence which stratifies infections according to severity is lacking.

P596 Risk of colorectal cancer and other malignancies in association with the use of thiopurines, tumour necrosis factor antagonists or mesalazine

Abstract Background Mesalazine, thiopurines and TNF antagonists play an important role in management of inflammatory bowel disease (IBD). It is generally accepted that longstanding ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). In addition to colorectal cancer, there are data that suggest that IBD is also associated with an increased risk of extra-intestinal malignancies but the results are inconclusive. The evidence concerning the effects of mesalazine on the risk of CRC in IBD patients remains conflicting. Methods In this review, cancer-reported outcomes with IBD drugs reported to FAERS (USA) were extracted for adalimumab, infliximab, thiopurines and mesalazine and compared with all other 25’382 drugs in the database. The data were used to calculate reporting odds ratio (ROR) and 95% CI for CRC, lymphoma, Hodgkin’s disease and all cancers outcomes. A sub-analysis was conducted to include patients exposed to mesalazine alone without IBD co-medications. Results The databases contained approximately 17 million reports for all drugs of which 401’084 were for adalimumab, 121 562 for infliximab, 11’985 for mesalazine, and 25’286 for thiopurines. Of these, a total of 259 757 concerned cancer-related AEs associated with the drugs under consideration. All IBD drugs were associated with a positive ROR for CRC with infliximab presenting the highest point estimate 8.01 (CI 95% 7.48–8.59) and adalimumab the lowest 2.52 (CI 95% 2.35–2.69). Considering patients exposed to only mesalazine, this association remained positive at 2.39 (CI 95% 1.58–3.59). For lymphoma, all IBD drugs also showed a positive ROR where thiopurines were associated with the highest 7.25 (CI 95% 6.69–7.84) and mesalazine with the lowest 1.46 (CI 95% 1.14 -2.73) point estimate. With regards to patients only exposed to mesalazine, the association showed protective effect, 0.24 (CI 95% 0.13–0.47). For Hodgkin’s disease again all IBD drugs showed a positive ROR where thiopurines were associated with the highest 34.65 (CI 95% 28.88–41.59) and adalimumab with the lowest 4.98 (CI 95% 4.39 -5.65) point estimate. In patients only exposed to mesalazine, no association 0.66 (CI 95% 0.09–4.66) was observed. Considering all cancers only positive ROR were observed where infliximab was associated with the highest 7.31 (CI 95% 7.17–7.45) and mesalazine with the lowest 1.33 (CI 95% 1.17–1.51) point estimate. In patients only exposed to mesalazine, a protective effect 0.73 (CI 95% 0.61–0.88) was observed. Conclusion FAERS data showed an association between reported occurrence of cancer and the drugs under consideration. Considering patients only exposed to mesalazine the odds ratio was positive only for colorectal cancer but lower than all other IBD drugs.

DOP25 Medication use and comorbidities among elderly when compared with younger patients with inflammatory bowel disease in the TARGET-IBD cohort

Abstract Background When compared with younger patients, much less is known regarding inflammatory bowel disease (IBD)-related medications in the elderly (&amp;gt;65 years) patients. This analysis uses a large cohort of patients with IBD to describe the distribution of patient characteristics and patterns of medication use. Methods TARGET-IBD is a longitudinal cohort of patients with IBD receiving usual care at community and academic practices in the US. Patients with IBD enrolled between July 2017 and May 2019 were included in this analysis. The prevalence of medication use by drug class at the time of enrolment among patients with both ulcerative colitis (UC) and Crohn’s disease (CD) was estimated. Age was stratified into the following categories: &amp;lt;30, 30–49, 50–65 and &amp;gt;65 years. Proportions and means of patient characteristics were compared using tests of association. The odds of biologic use at enrolment was modelled as was the 95% CI by patient characteristics using logistics regression. Results 681 patients with UC and 979 patients with CD were included in the analysis. At enrolment, mesalamine was the most common medication used among patients with CD &amp;gt;65 years (34%) and among patients with UC across all age categories (58%–77%, Table 1). The use of mesalamine generally increased with advancing age. Patients with CD &amp;gt;65 years were more than twice as likely to be users of mesalamine at enrolment than patients &amp;lt;30 years (p &amp;lt; 0.0001). Among patients with either disease type, anti-tumour necrosis factor α (anti-TNF) use decreased in patients &amp;gt;65 years compared with patients &amp;lt;30 years. Thiopurine use did not vary across age categories. Among patients &amp;gt;65 at enrolment, use of a 5-ASA derivative, anti-TNF, steroid, or thiopurine did not differ by established and newly diagnosed patients. There was no association between age, type of IBD, insurance, gender, race or cardiovascular disease and the odds of biologic use in patients &amp;gt;65 years (Figure 1). Conclusion Elderly patients with IBD, whether those with new diagnoses or individuals with the longstanding disease make up a substantial portion of the IBD population. Given that elderly patients demonstrate significant differences in medication use patterns compared with younger patients with IBD, studies of efficacy and adverse events specific to this population are warranted.

P246 Long-term prognosis of ulcerative colitis and its temporal changes between 1986 and 2015 in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea

Abstract Background No population-based study has evaluated the natural course of ulcerative colitis (UC) over three decades in non-Caucasians. We aimed to assess the long-term natural course of Korean patients with UC in a population-based cohort. Methods This Korean population-based SK-IBD cohort included all patients (N = 1013) newly diagnosed with UC during 1986–2015. Disease outcomes and their predictors were evaluated. Results During the median follow-up of 105 months, the overall use of systemic corticosteroids, thiopurines, and anti-tumour necrosis factor (TNF) agents was 40.8%, 13.9%, and 6.5%, respectively. Over time, the cumulative risk of commencing corticosteroids decreased, whereas that of commencing thiopurines and anti-TNF agents increased. During follow-up, 28.7% of 778 patients with proctitis or left-sided colitis at diagnosis experienced proximal disease extension. A total of 28 patients (2.8%) underwent colectomy, demonstrating cumulative risks of colectomy at 1, 5, 10, 20, and 30 years after diagnosis of 1.0%, 1.9%, 2.2%, 5.1%, and 6.4%, respectively. Multivariate Cox regression analysis revealed that extensive colitis at diagnosis (hazard ratio [HR] 8.249, 95% confidence interval [CI] 2.394–28.430), ever use of corticosteroids (HR 6.437, 95% CI 1.440–28.773), and diagnosis in the anti-TNF era (HR 0.224, 95% CI 0.057–0.886) were independent predictors of colectomy. The standardised mortality ratio in UC patients was 0.725 (95% CI 0.508–1.004). Conclusion Korean UC patients may have a better clinical course than Western patients, as indicated by a lower colectomy rate. The overall colectomy rate has continued to decrease over the past three decades.

P768 Long-term prognosis of Crohn’s disease and its temporal changes between 1986 and 2015 in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea

Abstract Background No previous population-based study has evaluated the natural course of Crohn’s disease (CD) over three decades in non-Caucasians. We previously reported a 30-year trend in the epidemiology of inflammatory bowel disease (IBD) in the Songpa-Kangdong (SK) District of Seoul, Korea between 1986 and 2015 (1). In this study, we aimed to analyse the long-term natural course of Korean patients with CD in the SK-IBD population-based cohort. Methods All patients newly diagnosed with CD between 1986 and 2015 were enrolled in this study. To assess the temporal trends in treatment paradigms and in the prognosis of CD, patients were divided into two cohorts according to the year of CD diagnosis: cohort 1, 1986–2003 and cohort 2, 2004–2015 (the anti-tumour necrosis factor [anti-TNF] era). Disease characteristics at diagnosis, outcomes and their predictors were evaluated. Results A total of 418 patients were enrolled. There were 318 males (76.1%) and median age at CD diagnosis was 22 years (interquartile range [IQR], 18–29). Disease location at CD diagnosis was ileal in 104 patients (24.9%), colonic in 39 (9.3%), and ileocolonic in 275 (65.8%). Disease behaviour at CD diagnosis was inflammatory in 339 patients (81.1%), stricturing in 34 (8.1%), and penetrating in 45 (10.8%). Perianal fistula/abscess was present in 43.3% (n = 181) before or at CD diagnosis. During the median follow-up of 108.1 months, the overall use of systemic corticosteroids, thiopurines, and anti-TNF agents was 57.4%, 80.9%, and 34.2%, respectively. Compared with the cohort 1, the cumulative probability of commencing corticosteroids decreased (p = 0.001), whereas that of commencing thiopurines and anti-TNF agents increased (both p &amp;lt; 0.001) in the cohort 2. A total of 113 patients (27.0%) underwent intestinal resection, demonstrating cumulative risks of intestinal resection at 1, 5, 10, 20, and 25 years after diagnosis of 12.5%, 16.5%, 25.6%, 49.7%, and 55.5%, respectively. Multivariate Cox regression analysis revealed that stricturing behaviour at diagnosis (hazard ratio [HR] 2.393, 95% confidence interval [CI] 1.234–4.641), penetrating behaviour at diagnosis (HR 4.514, 95% CI 1.752–11.629), and the cohort 2 (HR 0.530, 95% CI 0.297–0.945) were independent predictors of intestinal resection. The standardised mortality ratio was 1.867 (95% confidence interval, 0.502–4.780). Conclusion Korean patients showed a similar clinical course and intestinal resection rate compared with Western patients. The risk of intestinal resection has decreased in the anti-TNF era. Reference

Association Between Serological Markers and Crohn's Disease Activity.

BackgroundThe aim was to study the association between six serological markers and Crohn’s disease (CD) activity at an inflammatory bowel disease (IBD) referral center.MethodsWe designed a retrospective cohort study using adults (> 18 years) with CD followed for at least 1 year at University of Alabama at Birmingham. Baseline serological markers ASCA-IgA, ASCA-IgG, anti-OmpC IgA, anti-CBir1 IgG, anti-A4Fla2 IgG and anti-FlaX IgG were drawn at initial visit. Poisson regression was used to assess the longitudinal relationship between these markers drawn at baseline and rate of active clinical disease during follow-up.ResultsEach marker, from 135 patients, was categorized into high vs. low. A Poisson regression model adjusted for age, gender, race, duration of disease, obesity, proton pump inhibitor; steroid and thiopurine use, and disease location demonstrated that CD patients with high anti-CBir1 IgG at baseline were approximately twice more likely to have active clinical disease (incidence rate ratio (IRR) 2.06, 95% confidence interval (CI) 1.28 - 3.33, P = 0.0032). The unadjusted Poisson regression model for A4Fla2 IgG antibody level did suggest that a high A4Fla2 IgG at baseline was associated with a higher likelihood of active CD (IRR 1.64, 95% CI 1.07, 2.53, P = 0.0238) which however, upon adjustment based on effect size, was not significant. The other four antibodies did not appear to predict clinical course.ConclusionsHigh levels of anti-CBir1 IgG appear to be associated with a greater likelihood of active CD. Whether routine baseline testing for anti-CBir1 IgG to predict a more active clinical course is warranted needs more research.

Can We Predict the Toxicity and Response to Thiopurines in Inflammatory Bowel Diseases?

Thiopurines are a cheap, effective treatment option in the management of inflammatory bowel disease (IBD). However, with the growing choice of targeted therapies available, as well as the well-documented toxicities of thiopurines, the role of thiopurines has been questioned. Nevertheless, given their inexpense in an era of spiraling healthcare costs, thiopurines remain an attractive option in the right patients. In the age of personalized medicine, being able to predict patients who will respond as well as those that will develop toxicity to a treatment is vital to tailoring therapy. This review will summarize the available literature with respect to predictors of response and toxicity to thiopurines in order to guide management in IBD. Specifically, toxicities addressed will include myelotoxicity, hepatotoxicity, pancreatitis, alopecia, gastrointestinal and flu-like symptoms, and complications associated with Epstein-Barr virus. While more work needs to be done to further our ability to predict both response to and side effects from therapies, pharmacogenomic research shows significant promise in its ability to personalize our use of thiopurines.