scholarly journals P243 Changes in the therapeutic management of inflammatory bowel disease in the biological era – a nationwide retrospective cohort study in three Nordic countries: Results from the TRINordic study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S267-S267
Author(s):  
M Zhao ◽  
M Lördal ◽  
E Langholz ◽  
T Knudsen ◽  
M Voutilainen ◽  
...  

Abstract Background The use of biologic therapy has increased significantly during the last decade. In 2015, one in three Crohn’s disease (CD) patients and one in five ulcerative colitis (UC) patients had received biologics within 2 years of diagnosis 1 in Denmark (DEN), Sweden (SWE) and Norway (NOR). Whether this change in treatment strategy has resulted in changes in the use of conventional drugs (5-aminosalicylates [5-ASA], immunomodulators [IM] or corticosteroids) remains unknown. An aim of this study was to investigate the use of these drugs in the biological era.1 Høivik ML et al. Time to first treatment with biologic agents for ulcerative colitis and Crohn’s disease across four Nordic countries: Results from the TRINordic study, Submitted to ECCO 2020. Methods A total of 67,758 incident IBD patients (42,894 UC, 24,864 CD) diagnosed between 2010 to 2017 were included in a nationwide cohort in DEN, NOR and SWE. Information on drug treatment was extracted from the National Patient Registries and the National Prescription Registries. Patients were required to have at least 1-year of follow-up post-diagnosis; results are limited to patients diagnosed between 2010 to 2016, inclusive. Results During 2010 to 2016, cumulative exposure to 5-ASA in CD patients at 2 years after diagnosis declined from 19.0%, 39.0% and 50.5% in 2011 to 16.3%, 31.1% and 39.6% in 2016 in DEN, NOR and SWE, respectively (p < 0.001). The opposite trend was observed in UC where 87.3–91.1% received 5-ASA within 2 years in 2015 compared with 75.8–87.3% in 2011 (p < 0.001) (Figure 1). In all countries, corticosteroid use remained stable in CD with more than half of patients receiving corticosteroids within 2 years of diagnosis. In UC, corticosteroid use within 2 years of diagnosis increased in NOR from 42.2% in 2011 to 51.6% in 2015 (p < 0.001) but remained stable in DEN and SWE (Figure 2). The use of IM within 2 years increased in CD patients in NOR and SWE from 36.5% and 40.8% in 2010 to 51.3% and 52.1% in 2015 (p < 0.001). IM were less frequently used in UC but increased similarly from 14.0% and 21.1% in 2010 to 22.5% and 26.4% in 2015 (p < 0.001). In DEN, IM use remained stable over time (Figure 3). Conclusion The use of 5-ASA declined over time in patients diagnosed with CD but increased over time in patients diagnosed with UC. Corticosteroid use remained stable in CD but increased over time in UC patients in NOR. The increasing and earlier use of biologics was accompanied by increasing use of IM in all countries. While this could suggest a more aggressive treatment approach, differences in treatment practices across countries might contribute to these findings. The impact of changes in treatment strategies on disease outcomes remains to be shown.

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S261-S262
Author(s):  
M Lördal ◽  
J Burisch ◽  
E Langholz ◽  
T Knudsen ◽  
M Voutilainen ◽  
...  

Abstract Background Incidence and prevalence of inflammatory bowel diseases (IBD) have been increasing for the past decades in the western world, however with an emerging trend of incidence stabilisation in recent years. There is an indication of higher IBD incidence and prevalence in northern Europe, especially in the Nordic region, compared with southern Europe. Methods This retrospective observational study collected data from the National Patient Registries and National Prescription Registries (Sweden [SWE], Norway [NOR], Denmark [DEN]) and one university hospital database (Turku, Finland [FIN]) during 2010–2017 to investigate the annual incidence and prevalence of ulcerative colitis (UC) and Crohn’s disease (CD). Patients with ≥2 ICD-10 diagnosis codes for UC (K51) or CD (K50) from 2010 or later and no K51 or K50 codes prior to 2010 were included; patients were classified according to their last code. The look-back period for SWE was until 2000, for NOR until 2008, for DEN until 1995, and for FIN until 2004. Incidence proportions highlight results through 2016, as 2017 patients had less than 1-year follow-up. Results In total, 69,876 patients were included (SWE n = 27,902, NOR n = 20,761, FIN n = 2,118, DEN n = 19,095), of which 44 367 patients were diagnosed with UC and 25,509 with CD. In 2016, the annual incidence of UC was 28 patients per 100,000 persons in NOR, 32 patients per 100,000 persons in DEN, 25 patients per 100,000 persons in SWE, and 44 patients per 100,000 in FIN. The corresponding results for the annual incidence of CD per 100,000 persons were 22 in NOR, 16 in DEN, 16 in SWE, and 21 in FIN. The prevalence per 100,000 persons of both UC and CD was the highest in DEN, followed by SWE and NOR, and lowest in FIN. Prevalence estimates increased in all four Nordic countries during 2010–2017: for UC, from 409 to 488 patients in SWE, from 256 to 428 in NOR, from 129 to 375 in FIN, and from 577 to 798 in DEN. For CD, it increased from 261 to 313 patients in SWE, from 164 to 258 in NOR, from 54 to 164 in FIN, and from 280 to 400 in DEN. Conclusion This retrospective observational study showed that during 2016, the annual incidence of UC ranged from 25–44 patients per 100,000 persons across the evaluated Nordic countries, whereas the annual incidence of CD was 16–22 patients per 100,000 persons. Prevalence of both UC and CD increased during 2010–2017 in all four countries. Estimates of UC and CD incidence and prevalence in this analysis are greater than reported in the published literature. Additional analyses are underway to further explore the impact of methodological decisions on the estimates of UC and CD annual incidence and prevalence.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S060-S061
Author(s):  
M Høivik ◽  
M Lördal ◽  
J Burisch ◽  
E Langholz ◽  
T Knudsen ◽  
...  

Abstract Background Real-world data on time from diagnosis to first biologic treatment is limited for ulcerative colitis (UC) and Crohn’s disease (CD) patient populations. Methods This retrospective observational study collected data from the National Patient Registries and National Prescription Registries in Sweden (data on biologic use was only available for Stockholm [STK], Norway [NOR], Denmark [DEN]) and one university hospital database (Turku, Finland [FIN]) during 2010–2017 to investigate time from diagnosis to first biologic treatment for UC and CD. Patients with ≥2 ICD-10 diagnosis codes for UC (K51) or CD (K50) from 2010 or later were included; patients were classified according to their last code. The look-back period for SWE was until 2000, for NOR until 2008, for DEN until 1995, and for FIN until 2004. Time to first biologic was defined as the period from the first UC or CD code to first biologic record. In FIN, it was only possible to investigate infliximab (IFX). Results A total of 47,568 patients were included (STK n = 5594, NOR n = 20,761, FIN n = 2118, DEN n = 19,095). Of them, 30 397 patients had UC and 17 171 CD diagnosed during 2010–2017. Time to first biologic following diagnosis of UC or CD was decreased over time. For patients diagnosed with CD in 2015, in STK, NOR, FIN, and DEN, 30%, 35%, 25%, and 26%, respectively, received a biologic within 2 years; in 2010, the proportions were less than 10%, 20%, 5%, and 22%, respectively. FIN results may be attributed to only IFX use captured in the data sources. NOR had in most cohorts the shortest time between diagnosis and first treatment with a biologic agent, e.g. 33%, 35%, 36%, 34% and 33% of patients diagnosed with CD in 2011, 2012, 2013, 2014 and 2015, respectively, received a biologic already one month after diagnosis compared with 2%, 1%, 3%, 4% and 6%, respectively, in STK, 7%, 5%, 9%, 4% and 5%, respectively, in FIN and 3%, 10%, 28%, 12% and 23%, respectively, in DEN. Fewer UC than CD patients received biologics, but the time to first biologic was shortened to the same extent (Figure 1 and 2, respectively). In NOR, FIN and DEN, the most common biologic used was IFX for UC and CD, e.g. 18%, 14% and 15%, respectively, of UC and 35%, 17% and 35%, respectively, of CD patients diagnosed in 2015 had received IFX; in STK it was IFX for UC (8% of patients diagnosed in 2015) and adalimumab for CD (20% of patients diagnosed in 2015). Conclusion This retrospective observational study of >45 000 patients with inflammatory bowel disease in four Nordic countries showed reduced time between diagnosis and first biologic from 2010 to 2017, with the shortest time between diagnosis and first biologic in Norway. IFX was most commonly used.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S036-S037
Author(s):  
M Zhao ◽  
M Lördal ◽  
E Langholz ◽  
T Knudsen ◽  
M Voutilainen ◽  
...  

Abstract Background Biological therapy has been suggested to decrease surgery and hospitalisation risk in patients diagnosed with inflammatory bowel disease (IBD). During 2010 to 2016, the use of biologics in Denmark (DEN), Sweden (SWE) and Norway (NOR) increased dramatically and the time to first biologic treatment declined.1 However, the impact of increasing use of biologics on disease outcomes remains to be shown in real-life practice. In this nationwide study in three Nordic countries, we aimed to investigate trends in surgery and hospitalisation rates in IBD patients in the biological era.1 Høivik ML et al. Time to first treatment with biologic agents for Ulcerative Colitis and Crohn’s Disease across four Nordic countries: Results from the TRINordic study, Submitted to ECCO 2020. Methods A total number of 67 758 IBD patients (42 894 patients with ulcerative colitis (UC) and 24 864 Crohn’s disease (CD) diagnosed during the period from 2010 to 2017 in DEN, NOR and SWE were included using the National Patient Registries. Patients were required to have 1-year follow-up; results are limited to patients diagnosed between 2010 and 2016, inclusive. Using the unique personal identification number, individual-level information on surgery, hospitalisation and drug treatment were extracted from the National Patient Registries and the National Prescription Registries. Disease outcomes within two years after diagnosis were compared across annual cohorts. Results During 2010 to 2016, 2-year surgery rates in CD patients showed a non-significant decline from 11.9% in 2011 to 9.5% in 2016 in SWE while remaining stable in NOR and DEN (Figure 1). No temporal pattern in surgery risk was observed for UC. The proportion of CD patients being hospitalised within two years from diagnosis declined in SWE and NOR from 52.3% and 51.0% in 2011 to 47.3% and 38.5% in 2015 (p < 0.001), respectively, while hospitalisation in UC remained stable. In contrast, 2-year hospitalisation rates in DEN increased in CD from 27.0% in 2011 to 31.5% in 2016 (p = 0.045) and similarly in UC from 20.4 to 35.0% (p < 0.001), respectively (Figure 2). Conclusion No clear pattern was seen in two-year surgery and hospitalisation rates in IBD patients during 2010 to 2017 despite a concurrent increase in biological use in all countries. However, differences in treatment practices across countries might influence these findings. The impact of increased biological use on long-term outcomes in IBD remains to be shown.


2019 ◽  
Vol 13 (11) ◽  
pp. 1433-1438 ◽  
Author(s):  
Geoffrey C Nguyen ◽  
Lillian Du ◽  
Rachel Y Chong ◽  
Timothy D Jackson

Abstract Background The inflammatory bowel diseases [IBD], including Crohn’s disease [CD] and ulcerative colitis [UC], frequently lead to bowel surgery. Hypoalbuminaemia has been shown to be a prognostic factor for outcomes following surgery for other indications, and we sought to determine its role in predicting IBD-related postoperative outcomes. Methods We included patients who underwent IBD-related major abdominal surgery in the American College of Surgeons’ National Surgical Quality Improvement Program [ACS-NSQIP] between 2005 and 2012. We assessed the impact of indicators of protein-energy malnutrition [PEM] including hypoalbuminaemia, weight loss, and body mass index on postoperative outcomes. Results We identified 10 913 IBD patients [6082 Crohn’s disease and 4831 ulcerative colitis] who underwent bowel surgery. The prevalence of modest and severe hypoalbuminaemia was 17% and 24%, respectively; 30-day mortality was higher in Crohn’s patients with modest and severe hypoalbuminaemia compared with those with normal albumin levels preoperatively [0.7% vs 0.2%, p <0.05; 2.4% vs 0.2%, p <0.01]. The same was true for patients with UC with modest and severe hypoalbuminaemia [0.9% vs 0.1%, p <0.01; 5.6% vs 0.1%, p <0.01]. Overall infectious complications were more common in the presence of severe hypoalbuminaemia for CD [20% vs 13%, p <0.01]. and UC [28% vs 15%, p <0.01] patients. Last, there were higher rates of extra-intestinal, non-septic complications in both CD and UC patients with hypoalbuminaemia compared with those with normal albumin levels. Conclusions This study suggests that moderate-severe hypoalbuminaemia is associated with worse IBD-related postoperative outcomes and may have a role in preoperative risk stratification.


2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Christopher Moore ◽  
Shriram Jakate ◽  
Ali Keshavarzian

Inflammatory bowel disease (IBD) comprises the principal subtypes Crohn’s disease (CD) and ulcerative colitis (UC), with a fraction remaining as IBD unclassified (IBDU). Given the complexity of IBD manifestations in a patient over time and our increasing understanding of IBD biology, a modification in subtype diagnosis can also occur. Herein is a case of a 27-year-old female with well-controlled and long-standing pan-UC, who developed Crohn’s-like esophagogastroduodenitis. The difficulty in classifying IBD into a single traditional subtype, and the debated presentation of a coexistent IBD will be discussed.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S016-S017
Author(s):  
Q Zhang ◽  
L Fachal ◽  
R Shawky ◽  
M Parkes ◽  
C Anderson ◽  
...  

Abstract Background Patients with Crohn’s disease (CD) can develop complications including stricturing and penetrating disease [1, 2]. Although reliable baseline predictors of disease progression are urgently needed to inform management strategies, few studies have comprehensively explored the phenotypic and genetic determinants of disease progression in a sufficiently powered cohort. Methods We used data from 13,926 patients with CD in the UK IBD BioResource to investigate the effects of clinical phenotypes and genetics on CD progression. Median follow-up was 10.6 years and total follow-up was 193,033 patient-years. We applied the Montreal classification system to define disease as B1 (inflammatory), B2 (stricturing) and B3 (penetrating). Patients with B2 or B3 disease (N = 5,185) were compared to patients with B1 disease (N = 8,471) in a multivariate model fitted with both phenotype data and a polygenic score that we developed. Associations with q-values (false discovery rate adjusted p-values) less than 0.05 were defined as statistically significant. Results CD progression occurred over time from diagnosis (Figure 1). Consistent with previous findings, we confirmed factors including smoking, disease location and perianal disease were associated with disease progression [3] (Table 1). The impact of a genetic influence on disease progression was confirmed and shown to be independent of genetic effects on disease location [4]. Early prescription of medications showed a protective effect on disease progression: Infliximab, adalimumab and thiopurines significantly reduced the chance of B2/B3 progression when prescribed within two years of diagnosis. Additionally, we observed a decreased progression to B2/B3 disease in patients diagnosed recently (between 2012–2020) compared to those diagnosed before 2012. This finding persisted after conditioning on exposure to biologics and correcting for follow-up time and interval to first thiopurine prescription, and thus may be indicative of other improvements in standards of care in recent years. Conclusion Using a large, well-characterised cohort we confirm the importance of disease location, smoking status and genetics on disease progression. We highlight the positive impact of early medication prescription on disease progression and discover an independent signal relating to potential improvements in the standard of care in CD over time. These results create the framework for reliable predictors of CD progression that may better guide future CD management strategies. References


1994 ◽  
Vol 8 (7) ◽  
pp. 430-432 ◽  
Author(s):  
Robert N Allan

This paper summarizes our current knowledge of the role of the oral contraceptive pill in the pathogenesis of inflammatory bowel disease (IBO), followed by a review of fertility in women and men. IBD and pregnancy, including the impact on the fetus and the mother with ulcerative colitis or Crohn’s disease, is considered. The safety of drug treatment during pregnancy, the outcome of surgical treatment during pregnancy and the problems that may be encountered during pregnancy in patients with an ileostomy or ileo-anal pouch are discussed, followed by a review of the short and long term prognosis of ulcerative colitis and Crohn’s disease partition.


2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S57-S57
Author(s):  
Chaoyang Wang ◽  
Mazen Tolaymat ◽  
Raymond Cross

Abstract Background Anti-TNF drugs, adalimumab (ADA) and infliximab (IFX), are effective treatments for ulcerative colitis (UC) and Crohn’s disease (CD). However, 30% of patients do not respond to treatment (primary non-response) and 40% lose response over time (loss of response). Loss of response is often due to development of antibodies to ADA (ATA) and IFX (ATI). While it is known that undetectable or low ATA/ATI titers (&lt;200 ng/mL) are associated with better outcomes and high ATA/ATI titers (&gt;1000 ng/mL) are associated with poor outcomes, the significance of intermediate ATA/ATI titers (200–999 ng/mL) is not well understood. This study aims to investigate the impact of intermediate ATA/ATI titers on outcomes in CD and UC patients. Methods A retrospective chart review was conducted on CD and UC patients to determine associations between intermediate ATA/ATI titers and adverse clinical outcomes. The primary clinical outcome of interest is persistence on anti-TNF therapy 1 year after measurement of ATA/ATI titers. Secondary clinical outcomes of interest include clinical response to therapy 1 year after measurement of ATA/ATI titers. Participants consist of UC or CD patients treated with IFX or ADA at the University of Maryland IBD Program between October 2016 and October 2019 that had at least one measurement of ADA/ IFX and ATA/ATI during the study period. Results 376 patients were identified (ADA=157 and IFX=219). 271 of 322 low titer patients persisted on their original anti-TNF compared to 9 of 15 intermediate titer patients (p=0.026) and 1 of 10 high titer patients (p&lt;0.0001) (Table 1). The odds ratio (OR) of persistence comparing intermediate titer to low was 0.26 (0.09 to 0.80) and comparing high titer to low was 0.02 (0.00 to 0.14). In the low titer group, 47, 33, and 251 of 331 patients had no, partial, or complete response to therapy, respectively. In the intermediate titer group: 6, 1, and 8 of 15 patients, had no, partial or complete response; in the high titer group: 3, 1, and 3 of 10 patients, had no, partial, or complete response (Table 2). The difference in distribution of patients who showed no, partial, and complete response was significantly different between low titer patients and intermediate titer patients (p=0.019), but not different between intermediate titer and high titer patients (p=0.440). Conclusion Patients with intermediate titers were more likely than patients with low titers to lose response to anti-TNF and require a change anti-TNF therapy. Although our sample size of patients with intermediate titers was small, providers should consider dose optimization of anti-TNF with or without addition of an immune suppressant when intermediate titers are present. An alternative approach would be to repeat drug and antidrug antibody levels to assess for worsening pharmacokinetics. Persistence on original anti-TNF 1 year after first measurement in low, intermediate, and high titer patients (Fisher’s test). Response to therapy 1 year after first measurement in low, intermediate, and high titer patients (Fisher’s test).


2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 34-35 ◽  
Author(s):  
J W Windsor ◽  
M Buie ◽  
S Coward ◽  
R Gearry ◽  
T Hansen ◽  
...  

Abstract Background Inflammatory bowel disease (IBD) first presents in a population as cases of ulcerative colitis (UC) followed by cases of Crohn’s disease (CD). Newly industrialized countries (NIC) show a prallel epidemiology of IBD to highly industrialized countries (HIC) in the previous century; one marker of this is the relative incidence/prevalence rates of UC to CD, which approximates 1 over time. Aims Provide evidence for the UC:CD ratio as a proxy for disease penatrance in a population. Methods Systematic review of MedLine and Embase for studies reporting incidence or prevalence of UC and CD. Log-linear regression (by region and NIC/HIC [2019 United Nations definitions]) was used to calculate average annual percent change (AAPC) and associated 95% confidence intervals (CI). Data were plotted on an online, interactive map to show trends (link provided). Results We extracted data from 218 studies compising population-level data from 69 countries. We found negative AAPCs as the prevalence ratio of UC:CD significantly decreased over time in East Asia, West Asia, North Europe, and South Europe; 6/12 global regions displayed significantly decreasing incidence ratios. No AAPC was found to be significantly increasing (Table 1). When examing HIC/NIC, we found a significant effect of NIC on the UC:CD prevalence ratio after 2000 (AAPC:−3.83;95%CI:−6.28,−1.31) while HIC regions remained stable (AAPC:2.14;95%CI:−1.40,5.82). Looking at all available data, both HICs and NICs show significantly decreasing UC:CD prevalence ratios (HIC:AAPC:−3.72;95% CI:−4.46,−2.97; NIC:AAPC:−2.62;95%CI:−4.13,−1.08). Conclusions In some HICs (eg. Canada), the UC:CD incidence ratio was &lt;1 in the earliest available data (1966), explaining the stable AAPC in North America (AAPC:−0.24;95%CI:−1.12,0.65). However, in NICs (eg. Southern Asia), the AAPC is rapidly decreasing (AAPC:−24.68;95%CI:−37.85,−8.71) as areas like Sri Lanka rapidly fall from an incidence ratio of 7.5 (2007) to 2.8 (2012), mimicking trends in IBD epidimeology of HICs in the previous century. Funding Agencies None


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