Hot topics in Epidemiology from ECCO’19

One of the many difficult questions to answer has been the impact of biologic therapy on disease course. Complete remission with mucosal healing is postulated to reduce surgical rates by halting disease progression, thereby avoiding complications. Results from large-scale studies have been conflicting. Three studies presented at ECCO 2019 addressed this topic. The first, from the United Kingdom, used a hospital dataset linked to a prescription dataset. Within the limits of the study, the authors reported an association, albeit a non-significant one, between reduction in Ulcerative Colitis (UC) surgery rates and the introduction of infliximab in 2008 [2]. Similarly, while a decline in colectomy rates due to anti-TNF therapy was observed in a study from Denmark in 334 children and adolescents with UC, this reduction did not reach the level of significance. Instead the population showed a benefit in terms of reduced use of steroids following the start of anti-TNF therapy [3]. In contrast, analysis of a large administrative dataset from Quebec in Canada concerning a newly diagnosed population suggested an increased probability of major surgery during the years after the introduction of biologic drugs despite increasing use of these drugs [4].

Inherent limitations of retrospective studies are the indirect analysis of treatment and surgery rates as well as the assumption that prescription of biologic drugs is associated with remission. Studies investigating comparative surgical rates between patients receiving drug treatment versus no drug treatment and assessing disease activity to determine the association between remission and surgery may explain some of these inconsistent findings. A post-hoc analysis of GEMINI trials addressed the issue of effects on surgical rates and showed a lower rate of surgery with vedolizumab (VDZ) therapy versus placebo at one year. In patients who continued VDZ therapy for five years, low rates of surgical intervention were observed [5]. Another potential confounder is disease duration. Disease duration within the GEMINI studies was >7 years, raising the question of whether administration of biologic therapy early in the disease course might influence outcomes to a greater extent. In a paediatric population, surgical resection rates declined with increasing use of anti-TNF drugs in CD but not UC. It is noteworthy that in this study, anti-TNF therapy within three years of diagnosis had a greater impact on surgical rates [6]. Further studies with a higher surgical event rate and collecting additional variables such as short disease duration before biologic therapy and correlation between response to biologic therapy and measures of disease activity would be invaluable in clarifying the impact on surgery rates.

The emergence of IBD as an epidemic in low-incidence countries has opened up the potential for studies of the risk factors underlying this trend. Abstracts presented from Brazil, Iran, Thailand, Singapore and French Polynesia all highlighted the global impact of IBD and the introduction of databases or registries to monitor disease patterns. The incidence in French Polynesia remains the lowest among Eastern countries [7–11].

Similarly, studies are required to explore the causes and risk factors underlying temporal trends in populations in high-incidence countries. In this context, observations stemming from well-developed databases were presented, addressing the alarming rise in incidence and prevalence in Scotland and the continued rise in Israel, the United States and Spain [12–15].

Reports on treatment outcomes across IBD population cohorts in Denmark and Sweden and across Europe offered a better understanding of treatment patterns and outcomes in response to different therapeutic interventions. A study in Denmark compared outcomes of combination therapy with thiopurine and allopurinol versus thiopurine monotherapy in 10,367 IBD patients [16]. No significant differences were noted between the groups with regard to either benefits (surgery, hospitalisation) or risks (adverse events), even though previous studies have indicated improved clinical remission with the studied combination. Drug survival assessed through the Swedish database was greater for adalimumab than for infliximab, both when it was used as a first-line anti-TNF drug and when it was used as a second-line treatment. This result encourages use of adalimumab as a first-line biologic in CD [17]. In the Epi-IBD study, elderly patients were found to have received less aggressive therapy; further studies are needed to explore the reason for this, and particularly whether the finding reflects a less severe disease course in late-onset IBD [18].

The nature of the relation between cancer and IBD is an important topic, and two abstracts presented findings on the increased risk of cancer in patients with paediatric-onset IBD [19, 20]. In another study, the risk of colorectal cancer following low-grade dysplasia (LGD) was explored in a Dutch cohort of 1215 IBD patients with colonic LGD. The significance of LGD recurrence at a subsequent surveillance colonoscopy was investigated in comparison with absence of such recurrence. It was found that 21.3% of patients developed a recurrence of LGD within three years of the index lesion. Within this group, 17.8% developed subsequent advanced neoplasia compared with 10% without a second LGD lesion, suggesting that LGD recurrence is a high-risk precursor of future cancer [21].

Epidemiology research continues to address questions of clinical importance. Progress is anticipated through the acquisition of large prospective datasets that collect specific standardised variables as well as the harmonisation of data across databases to enable collaborative studies across the world. These measures may help to close the gaps in knowledge, and one may look forward to presentation of further illuminating studies at future ECCO Congresses.

References

1. Kuller LH. Epidemiology: then and now. Am J Epidemiol. 2016:183:372–80.
2. Worley G, Almoudaris A, Bassett P, et al. A nationwide cohort study of colectomy rates for ulcerative colitis during the introduction of biologic therapy. Journal of Crohn's and Colitis 2019;13: S065.
3. Lund K, Larsen MD, Knudsen T, et al. Anti-TNF-α therapy, use of corticosteroids, and colectomy among paediatric and adolescent patients with ulcerative colitis: a nationwide study Denmark. Journal of Crohn's and Colitis 2019;13: S442.
4. Verdon C, Reinglas J, Coulombe J, et al. Surgery and hospitalisations rates in inflammatory bowel disease patients in the Québec provincial database from 199–6 to 2015. Journal of Crohn's and Colitis 2019;13: S075.
5. Feagan BG, Sands BE, Lirio R, et al.  Effect of vedolizumab on surgical rates in IBD post hoc analysis from the GEMINI trials. Journal of Crohn's and Colitis 2019;13: S077.
6. Ashton JJ, Borca F, Mossotto E, et al. A significant decline in surgical resections during childhood with increased prevalence of anti-TNF therapy in patients with paediatric inflammatory bowel disease. Journal of Crohn's and Colitis 2019;13: S494.
7. Parra RS, Feitosa MR, Ferreira SC, et al. Inflammatory bowel disease epidemiology a tertiary centre in Brazil. Journal of Crohn's and Colitis 2019;13: S214.
8. Malekzadeh M, Sima A, Alatab S, et al. Iranian Registry of Crohn’s and Colitis (IRCC): first nation-wide IBD registry in Middle East, a study protocol. Journal of Crohn's and Colitis 2019;13: S492.
9. Aniwan S, Limsrivilai J. Differences among disease pattern, medication use, surgery and hospitalisation rates in a low prevalence of ulcerative colitis population: A retrospective cohort from Bangkok, Thailand. Journal of Crohn's and Colitis 2019;13: S504.
10. Grymonpré V, Loria A, Beaugendre E, et al. Epidemiology of inflammatory bowel diseases in French Polynesia. Journal of Crohn's and Colitis 2019;13: S506.
11. Chan WPW, Lim MS, Tan AXH, et al. Phenotype and natural history of inflammatory bowel disease: results from the largest centre in Singapore. Journal of Crohn's and Colitis 2019;13: S518.
12. C. Burgess C, Henderson P. Chalmers I, et al. Nationwide incidence and prevalence of paediatric inflammatory bowel disease in Scotland 2015–2017 demonstrates the highest paediatric prevalence rate recorded worldwide. Journal of Crohn's and Colitis 2019;13: S081.
13. Friedman M, Navon D, Asayag N, et al. The prevalence of inflammatory bowel disease doubled in the last decade in Israel: an epiIIRN national population-based study.  Journal of Crohn's and Colitis 2019;13: S513.
14. Hunter T, Naegeli A, Dong Y, et al. Increasing trends in prevalence and treatment patterns of paediatric ulcerative colitis patients in the USA. Journal of Crohn's and Colitis 2019;13: S519.
15. Chaparro M, Barreiro-de Acosta M, Benítez J, et al. Epidemiology, clinical characteristics, evolution and treatments in newly diagnosed inflammatory bowel disease (IBD): results from the nationwide EpidemIBD study of GETECCU. Journal of Crohn's and Colitis 2019;13: S516.
16. Thomsen SB, Allin KH, Burisch J, et al. Thiopurine and allopurinol combination therapy and the risk of adverse outcomes and step-up medical therapy in inflammatory bowel disease patients: a nationwide Danish cohort study. Journal of Crohn's and Colitis 2019;13: S083.
17. Visuri I, Eriksson C, Mårdberg E, et al. Anti-TNF agent drug survival in patients with IBD: real-world comparisons of individual anti- TNF agents based on the Swedish National Quality Registry for IBD (SWIBREG). Journal of Crohn's and Colitis 2019;13: S443.
18. Hernandez V, Martinez-Cadilla J, Langholz E, et al. Medical treatment and surgery in patients with elderly-onset inflammatory bowel disease: 3-year follow-up of Epi-IBD 2010-2011 cohorts. Journal of Crohn's and Colitis 2019;13: S510.
19. Malham M, Jakobsen C, Paerregaard A, et al. The cancer incidence in paediatric onset inflammatory bowel disease: a population-based study from Denmark. Journal of Crohn's and Colitis 2019;13: S509.
20. Kjærgaard VS, Jensen CB, Burisch J, et al. Risk of cancer in paediatric onset inflammatory bowel disease: a nationwide cohort study 1977–2014. Journal of Crohn's and Colitis 2019;13: S510.
21. de Jong M, Kanne H, Nissen L, et al. Increased risk of advanced neoplasia in inflammatory bowel disease patients with recurrent low-grade dysplasia. Journal of Crohn's and Colitis 2019;13: S073.