Contemporary Risk of Surgery in Patients With Ulcerative Colitis and Crohn’s Disease: A Meta-Analysis of Population-Based Cohorts

Published:October 27, 2020DOI:https://doi.org/10.1016/j.cgh.2020.10.039

      Background & Aims

      We conducted a systematic review with meta-analysis to estimate rates and trends of colectomy in patients with ulcerative colitis (UC), and of primary and re-resection in patients with Crohn’s disease (CD), focusing on contemporary risks.

      Methods

      Through a systematic review until September 3, 2019, we identified population-based cohort studies that reported patient-level cumulative risk of surgery in patients with UC and CD. We evaluated overall and contemporary risk (after 2000) of surgery and analyzed time trends through mixed-effects meta-regression.

      Results

      In patients with UC (26 studies), the overall 1-, 5-, and 10-year risks of colectomy was 4.0% (95% CI, 3.3–5.0), 8.8% (95% CI, 7.7–10.0), and 13.3% (95% CI, 11.3–15.5), respectively, with a decrease in risk over time (P < .001). Corresponding contemporary risks were 2.8% (95% CI, 2.0–3.9), 7.0% (95% CI, 5.7–8.6), and 9.6% (95% CI, 6.3–14.2), respectively. In patients with CD (22 studies), the overall 1-, 5-, and 10-year risk of surgery was 18.7% (95% CI, 15.0–23.0), 28.0% (95% CI, 24.0–32.4), and 39.5% (95% CI, 33.3–46.2), respectively, with a decrease in risk over time (P < .001). Corresponding contemporary risks were 12.3% (95% CI, 10.8–14.0), 18.0% (95% CI, 15.4–21.0), and 26.2% (95% CI, 23.4–29.4), respectively. In a meta-analysis of 8 studies in patients with CD with prior resection, the cumulative risk of a second resection at 5 and 10 years after the first resection was 17.7% (95% CI, 13.5–22.9) and 31.3% (95% CI, 24.1–39.6), respectively.

      Conclusions

      Patient-level risks of surgery have decreased significantly over time, with a 5-year cumulative risk of surgery of 7.0% in UC and 18.0% in CD in contemporary cohorts. This decrease may be related to early detection and/or better treatment.

      Graphical abstract

      Keywords

      Abbreviations used in this paper:

      CD (Crohn’s disease), IBD (inflammatory bowel disease), I2 (inconsistency index), UC (ulcerative colitis)
      See editorial on page 2029.
      The global incidence and prevalence of inflammatory bowel disease (IBD) is increasing.
      • Ng S.C.
      • Shi H.Y.
      • Hamidi N.
      • et al.
      Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies.
      By 2030, the disease is estimated to affect 1% of individuals in the Western world. IBD is characterized by a lifelong, unpredictable, relapsing-remitting course, leading to substantial morbidity, diminished quality of life, and increased health care resource utilization.
      • Coward S.
      • Clement F.
      • Benchimol E.I.
      • et al.
      Past and future burden of inflammatory bowel diseases based on modeling of population-based data.
      Approximately 80% of patients require hospitalization, with 25% being re-admitted within 30 to 90 days of admission.
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      • Panaccione N.
      • et al.
      Trends in hospitalisation rates for inflammatory bowel disease in Western versus newly industrialised countries: a population-based study of countries in the Organisation for Economic Co-operation and Development.
      ,
      • Nguyen N.H.
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      • Dulai P.S.
      • et al.
      Rate of risk factors for and interventions to reduce hospital readmission in patients with inflammatory bowel diseases.
      A prior meta-analysis suggested that approximately one third of patients with Crohn’s disease (CD) require surgery within 5 years of their diagnosis, with the number increasing to nearly 50% within 10 years of their diagnosis.
      • Frolkis A.D.
      • Dykeman J.
      • Negron M.E.
      • et al.
      Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies.
      Similarly, approximately 1 in 6 patients with ulcerative colitis (UC) undergo colectomy within 10 years of their diagnosis. However, the number of cohorts reporting contemporary surgical risk in patients diagnosed in the 21st century was very small in this meta-analysis. Over the past 2 decades, several therapeutic measures have improved disease outcomes, including the following: (1) earlier diagnosis, (2) changes in approach to management of IBD with targeted use of disease-modifying immunosuppressive therapy, (3) introduction and increasing uptake of biologic agents such as tumor necrosis factor-α antagonists, and (4) earlier detection and endoscopic management of colorectal neoplasia.
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      • Mehandru S.
      • Allen P.B.
      • et al.
      Ulcerative colitis.
      • Torres J.
      • Mehandru S.
      • Colombel J.F.
      • et al.
      Crohn's disease.
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      • et al.
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      Accordingly, several studies variably have shown a decrease in risk of surgery over the past 2 decades.
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      • Lord R.
      • Hull M.A.
      • et al.
      Decreasing risk of first and subsequent surgeries in patients with Crohn's disease in England from 1994 through 2013.
      • Shinagawa T.
      • Hata K.
      • Ikeuchi H.
      • et al.
      Rate of reoperation decreased significantly after year 2002 in patients with Crohn's disease.
      • Rungoe C.
      • Langholz E.
      • Andersson M.
      • et al.
      Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011.
      To better understand surgical risk of IBD in contemporary cohorts, we performed a systematic review with meta-analysis to analyze the cumulative 1-, 5-, and 10-year risks of major abdominal surgery (and repeat surgery in patients with CD) in patients with UC and CD, in population-based inception cohorts.

      Methods

      We performed this systematic review based on an a priori protocol and reported our findings according to the guidelines as prescribed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • et al.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

       Study Selection

      We included population-based cohort studies in patients with incident UC and/or CD, reporting the cumulative risk of major abdominal surgery since their diagnosis, with at least a 1-year minimum follow-up period. Population-based studies were identified as those that investigated the entire population in a defined geographic area in a defined time period, used appropriate sampling techniques to infer risk for the entire population, or used national registries capturing nearly the entire population in a region (>90%). For inclusion, these studies were required to report the number of patients with incident UC or CD (or the number of patients with incident CD with initial abdominal surgery to analyze the risk of repeat surgery), calendar year of cohort recruitment, and the cumulative risk of surgery estimated by Kaplan–Meier methodology. When multiple studies reported surgical risk from the same cohort, the most comprehensive study reporting from nonoverlapping times was included.
      We excluded the following studies: (1) studies that reported only overall annual surgical rates without patient-level cumulative risk of surgery; (2) studies that reported risk of surgery in patients with IBD, without distinguishing CD or UC; (3) were not population-based (single-center or multicenter referral studies, or clinical trials); or (4) reported the incidence rate of surgery without cumulative risk.

       Search Strategy, Data Extraction, and Risk of Bias Assessment

      Details of the search strategy are reported in the "Data Sources and Search Strategy" section and Supplementary Table 1 in the Supplementary Methods. Data extraction and risk of bias assessment are reported in the "Data Extraction and Risk of Bias Assessment" section in the Supplementary Methods. Supplementary Methods can be found in the Supplementary Appendix.

       Outcomes

      The primary outcome was the cumulative 1-, 5-, and 10-year risks of major abdominal surgery in patients with UC (defined as colectomy with or without an ileal pouch–anal anastomosis) and CD (intestinal resection in patients with CD), and the 5- and 10-year risks of repeat major abdominal surgery in patients with CD with initial intestinal resection. Although most studies reported cumulative risk at 1, 5, and 10 years, there were some instances in which different cumulative risk at different years was reported. As such, we grouped 1- to 3-year risk as 1-year risk, 4- to 6-year risk as 5-year risk, and 7- to 10-year risk as 10-year risk.
      Subsequently, to estimate contemporary risks of surgery in patients diagnosed with IBD in the 21st century, we performed an analysis of cohorts in which the majority of patients were diagnosed after 2000 (>90% cohort).

       Statistical Analysis

      The pooled risk of major abdominal surgery and 95% CIs at 1, 5, and 10 years for both UC and CD, and the 5- and 10-year risk of repeat abdominal surgery in patients with CD with prior resection, was estimated using a random-effects model.
      • DerSimonian R.
      • Laird N.
      Meta-analysis in clinical trials.
      To estimate 95% CIs for individual study estimates from Kaplan–Meier curves, we assumed complete follow-up evaluation of the entire cohort. For time-trend analyses, to assess changes in surgical risk over time, the start year of inclusion of patients with incident UC and CD was included as a continuous variable in a meta-regression model of all studies.
      • Frolkis A.D.
      • Dykeman J.
      • Negron M.E.
      • et al.
      Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies.
      When the slope of the surgery incidences fit by the mixed-effect model had an associated P value of less than .05, we concluded that the incidence of surgery was changing significantly over time.
      Heterogeneity between studies was assessed using the inconsistency index (I2), with values greater than 50% suggesting significant heterogeneity.
      • Higgins J.P.
      • Thompson S.G.
      • Deeks J.J.
      • et al.
      Measuring inconsistency in meta-analyses.
      We anticipated high statistical heterogeneity as a meta-analysis of cumulative incidence, and took measures to address this in the design stage (strict study inclusion/exclusion criteria) and analysis. We performed subgroup analyses based on geographic location (North America vs Europe vs other geographic locations) and age of cohort, with a P value for differences between subgroups of less than .10 considered statistically significant. We also conducted mixed-effects meta-regression based on population composition (proportion of males) and disease characteristics (UC: proportion of patients with extensive colitis [E3 on the Montreal classification]; CD: proportion of patients with ileum-dominant CD [L1/L3 on the Montreal classification], proportion of patients with penetrating and/or fibrostenotic behavior [B2/B3 on the Montreal classification]); specific data on age at cohort entry was not reported consistently. Sensitivity analyses were performed to exclude conference proceedings, and to estimate the 10-year risk of surgery, by excluding studies in which the median population follow-up evaluation since diagnosis was shorter than 5 years or was not reported. Publication bias was assessed quantitatively using the Egger regression test (publication bias was considered present if P ≤ .10), and was assessed qualitatively by visual inspection of funnel plots.
      • Sterne J.A.
      • Egger M.
      • Smith G.D.
      Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis.
      All analyses were performed using Comprehensive Meta-Analysis software, version 2 (Biostat, Englewood, NJ).

      Results

      A total 5138 unique studies were identified using our search strategy. Of these, 137 full-text articles were reviewed, and 44 studies were included in quantitative synthesis, reporting on 26 cohorts of patients with UC,
      • Rungoe C.
      • Langholz E.
      • Andersson M.
      • et al.
      Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011.
      ,
      • Benchimol E.
      • Guttmann A.
      • To T.
      • et al.
      Changes in surgical and hospitalization rates in pediatric inflammatory bowel disease in Ontario, Canada (1994-2007).
      • Charpentier C.
      • Salleron J.
      • Savoye G.
      • et al.
      Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study.
      • Chhaya V.
      • Saxena S.
      • Cecil E.
      • et al.
      The impact of timing and duration of thiopurine treatment on colectomy in ulcerative colitis: a national population-based study of incident cases between 1989-2009.
      • Chow D.K.
      • Leong R.W.
      • Tsoi K.K.
      • et al.
      Long-term follow-up of ulcerative colitis in the Chinese population.
      • Eriksson C.
      • Cao Y.
      • Rundquist S.
      • et al.
      Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Orebro, Sweden, 1963-2010.
      • Gheorghe C.
      • Pascu O.
      • Gheorghe L.
      • et al.
      Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study.
      • Gower-Rousseau C.
      • Sarter H.
      • Turck D.
      • et al.
      Long-term outcome of paediatric-onset ulcerative colitis: early years are shaping the future.
      • Guasch M.
      • Clos A.
      • Ordas I.
      • et al.
      The availability of anti-TNF agents is associated with reduced early surgical requirements in Crohn's disease but not in ulcerative colitis. A nationwide study from the Eneida registry.
      • Lakatos L.
      • Kiss L.S.
      • David G.
      • et al.
      Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002-2006.
      • Langholz E.
      • Munkholm P.
      • Krasilnikoff P.A.
      • et al.
      Inflammatory bowel diseases with onset in childhood. Clinical features, morbidity, and mortality in a regional cohort.
      • Leijonmarck C.E.
      • Persson P.G.
      • Hellers G.
      Factors affecting colectomy rate in ulcerative colitis: an epidemiologic study.
      • Lirhus S.S.
      • Hoivik M.L.
      • Moum B.
      • et al.
      Regional differences in anti-TNF-alpha therapy and surgery in the treatment of inflammatory bowel disease patients: a Norwegian nationwide cohort study.
      • Lund K.
      • Larsen M.D.
      • Knudsen T.
      • et al.
      Anti-TNF-alpha therapy, use of corticosteroids, and colectomy among paediatric and adolescent patients with ulcerative colitis: a nationwide study.
      • Malaty H.M.
      • Abraham B.P.
      • Mehta S.
      • et al.
      The natural history of ulcerative colitis in a pediatric population: a follow-up population-based cohort study.
      • Nguyen G.C.
      • Bernstein C.N.
      • Benchimol E.I.
      Risk of surgery and mortality in elderly-onset inflammatory bowel disease: a population-based cohort study.
      • Niewiadomski O.
      • Studd C.
      • Hair C.
      • et al.
      Prospective population-based cohort of inflammatory bowel disease in the biologics era: disease course and predictors of severity.
      • Nordenvall C.
      • Rosvall O.
      • Bottai M.
      • et al.
      Surgical treatment in childhood-onset inflammatory bowel disease-a nationwide register-based study of 4695 incident patients in Sweden 2002-2014.
      • O'Keefe E.A.
      • Wright J.P.
      • Froggatt J.
      • et al.
      Medium-term follow-up of ulcerative colitis in Cape Town.
      • Parragi L.
      • Fournier N.
      • Zeitz J.
      • et al.
      Colectomy rates in ulcerative colitis are low and decreasing: 10-year follow-up data from the Swiss IBD cohort study.
      • Probert C.S.J.
      • Bhakta P.
      • Wicks T.C.B.
      • et al.
      How necessary is colectomy? An epidemiological study of the surgical management of ulcerative colitis amongst different ethnic groups in Leicestershire.
      • Ronnblom A.
      • Holmstrom T.
      • Tanghoj H.
      • et al.
      Low colectomy rate five years after diagnosis of ulcerative colitis. Results from a prospective population-based cohort in Sweden (ICURE) diagnosed during 2005-2009.
      • Samuel S.
      • Ingle S.B.
      • Dhillon S.
      • et al.
      Cumulative incidence and risk factors for hospitalization and surgery in a population-based cohort of ulcerative colitis.
      • Solberg I.C.
      • Lygren I.
      • Jahnsen J.
      • et al.
      Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN study).
      • Spizzo P.
      • Hair C.
      • Beswick L.
      • et al.
      A combined cohort IBD natural history study: high rates of immunomodulator and biologic use, low rates of intestinal surgery for Crohn's disease.
      • Targownik L.E.
      • Singh H.
      • Nugent Z.
      • et al.
      The epidemiology of colectomy in ulcerative colitis: results from a population-based cohort.
      22 cohorts of patients with CD,
      • Burr N.E.
      • Lord R.
      • Hull M.A.
      • et al.
      Decreasing risk of first and subsequent surgeries in patients with Crohn's disease in England from 1994 through 2013.
      ,
      • Rungoe C.
      • Langholz E.
      • Andersson M.
      • et al.
      Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011.
      ,
      • Charpentier C.
      • Salleron J.
      • Savoye G.
      • et al.
      Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study.
      ,
      • Gheorghe C.
      • Pascu O.
      • Gheorghe L.
      • et al.
      Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study.
      ,
      • Guasch M.
      • Clos A.
      • Ordas I.
      • et al.
      The availability of anti-TNF agents is associated with reduced early surgical requirements in Crohn's disease but not in ulcerative colitis. A nationwide study from the Eneida registry.
      ,
      • Lirhus S.S.
      • Hoivik M.L.
      • Moum B.
      • et al.
      Regional differences in anti-TNF-alpha therapy and surgery in the treatment of inflammatory bowel disease patients: a Norwegian nationwide cohort study.
      ,
      • Nguyen G.C.
      • Bernstein C.N.
      • Benchimol E.I.
      Risk of surgery and mortality in elderly-onset inflammatory bowel disease: a population-based cohort study.
      • Niewiadomski O.
      • Studd C.
      • Hair C.
      • et al.
      Prospective population-based cohort of inflammatory bowel disease in the biologics era: disease course and predictors of severity.
      • Nordenvall C.
      • Rosvall O.
      • Bottai M.
      • et al.
      Surgical treatment in childhood-onset inflammatory bowel disease-a nationwide register-based study of 4695 incident patients in Sweden 2002-2014.
      ,
      • Spizzo P.
      • Hair C.
      • Beswick L.
      • et al.
      A combined cohort IBD natural history study: high rates of immunomodulator and biologic use, low rates of intestinal surgery for Crohn's disease.
      ,
      • Bernell O.
      • Lapidus A.
      • Hellers G.
      Risk factors for surgery and postoperative recurrence in Crohn's disease.
      • Chatu S.
      • Saxena S.
      • Subramanian V.
      • et al.
      The impact of timing and duration of thiopurine treatment on first intestinal resection in Crohn's disease: national UK population-based study 1989-2010.
      • Jeuring S.
      • Van Den Heuvel T.
      • Zeegers M.
      • et al.
      Hospitalisation and surgery risk in Crohn's disease in the biological era - results from the Dutch population-based IBD-SL cohort.
      • Lakatos P.L.
      • Golovics P.A.
      • David G.
      • et al.
      Has there been a change in the natural history of Crohn's disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009.
      • O'Keefe E.A.
      • Wright J.P.
      • Froggatt J.
      • et al.
      Medium-term follow-up of Crohn's disease in Cape Town.
      • Pandey A.
      • Salazar E.
      • Kong C.S.C.
      • et al.
      Risk of major abdominal surgery in an Asian population-based Crohn's disease cohort.
      • Peneau A.
      • Salleron J.
      • Fumery M.
      • et al.
      Long-term outcome of paediatric-onset Crohn's disease: a population-based study.
      • Peyrin-Biroulet L.
      • Harmsen W.S.
      • Tremaine W.J.
      • et al.
      Surgery in a population-based cohort of Crohn's disease from Olmsted County, Minnesota (1970-2004).
      • Rabilloud M.L.
      • Bretagne J.F.
      • Bajeux E.
      • et al.
      Predictive factors of surgery and bowel damage during the course of Crohn's disease: a population-based study.
      • Ramadas A.V.
      • Gunesh S.
      • Thomas G.A.O.
      • et al.
      Natural history of Crohn's disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates.
      • Solberg I.C.
      • Vatn M.H.
      • Hoie O.
      • et al.
      Clinical course in Crohn's disease: results of a Norwegian population-based ten-year follow-up study.
      • Zhulina Y.
      • Udumyan R.
      • Tysk C.
      • et al.
      The changing face of Crohn's disease: a population-based study of the natural history of Crohn's disease in Orebro, Sweden 1963-2005.
      and 8 cohorts of patients with CD with prior surgery.
      • Burr N.E.
      • Lord R.
      • Hull M.A.
      • et al.
      Decreasing risk of first and subsequent surgeries in patients with Crohn's disease in England from 1994 through 2013.
      ,
      • Shinagawa T.
      • Hata K.
      • Ikeuchi H.
      • et al.
      Rate of reoperation decreased significantly after year 2002 in patients with Crohn's disease.
      ,
      • O'Keefe E.A.
      • Wright J.P.
      • Froggatt J.
      • et al.
      Medium-term follow-up of Crohn's disease in Cape Town.
      ,
      • Beelen E.M.J.
      • van der Woude C.J.
      • Pierik M.J.
      • et al.
      Decreasing trends in intestinal resection and re-resection in Crohn's disease: a nationwide cohort study.
      • Benchimol E.
      • Boualit M.
      • Wong J.
      • et al.
      Predictors of the need for second intestinal resection in children with Crohn's disease.
      • Boualit M.
      • Salleron J.
      • Turck D.
      • et al.
      Long-term outcome after first intestinal resection in pediatric-onset Crohn's disease: a population-based study.
      • Nguyen G.C.
      • Saibil F.
      • Steinhart A.H.
      • et al.
      Postoperative health-care utilization in Crohn's disease: the impact of specialist care.
      • Vester-Andersen M.K.
      • Vind I.
      • Prosberg M.V.
      • et al.
      Hospitalisation, surgical and medical recurrence rates in inflammatory bowel disease 2003-2011-a Danish population-based cohort study.
      Ninety-three studies were excluded, with detailed reasons reported in Supplementary Figure 1.

       Cumulative Risk of Colectomy in Patients With Ulcerative Colitis

      Table 1 details the characteristics of 26 studies in patients with UC.
      • Rungoe C.
      • Langholz E.
      • Andersson M.
      • et al.
      Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011.
      ,
      • Benchimol E.
      • Guttmann A.
      • To T.
      • et al.
      Changes in surgical and hospitalization rates in pediatric inflammatory bowel disease in Ontario, Canada (1994-2007).
      • Charpentier C.
      • Salleron J.
      • Savoye G.
      • et al.
      Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study.
      • Chhaya V.
      • Saxena S.
      • Cecil E.
      • et al.
      The impact of timing and duration of thiopurine treatment on colectomy in ulcerative colitis: a national population-based study of incident cases between 1989-2009.
      • Chow D.K.
      • Leong R.W.
      • Tsoi K.K.
      • et al.
      Long-term follow-up of ulcerative colitis in the Chinese population.
      • Eriksson C.
      • Cao Y.
      • Rundquist S.
      • et al.
      Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Orebro, Sweden, 1963-2010.
      • Gheorghe C.
      • Pascu O.
      • Gheorghe L.
      • et al.
      Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study.
      • Gower-Rousseau C.
      • Sarter H.
      • Turck D.
      • et al.
      Long-term outcome of paediatric-onset ulcerative colitis: early years are shaping the future.
      • Guasch M.
      • Clos A.
      • Ordas I.
      • et al.
      The availability of anti-TNF agents is associated with reduced early surgical requirements in Crohn's disease but not in ulcerative colitis. A nationwide study from the Eneida registry.
      • Lakatos L.
      • Kiss L.S.
      • David G.
      • et al.
      Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002-2006.
      • Langholz E.
      • Munkholm P.
      • Krasilnikoff P.A.
      • et al.
      Inflammatory bowel diseases with onset in childhood. Clinical features, morbidity, and mortality in a regional cohort.
      • Leijonmarck C.E.
      • Persson P.G.
      • Hellers G.
      Factors affecting colectomy rate in ulcerative colitis: an epidemiologic study.
      • Lirhus S.S.
      • Hoivik M.L.
      • Moum B.
      • et al.
      Regional differences in anti-TNF-alpha therapy and surgery in the treatment of inflammatory bowel disease patients: a Norwegian nationwide cohort study.
      • Lund K.
      • Larsen M.D.
      • Knudsen T.
      • et al.
      Anti-TNF-alpha therapy, use of corticosteroids, and colectomy among paediatric and adolescent patients with ulcerative colitis: a nationwide study.
      • Malaty H.M.
      • Abraham B.P.
      • Mehta S.
      • et al.
      The natural history of ulcerative colitis in a pediatric population: a follow-up population-based cohort study.
      • Nguyen G.C.
      • Bernstein C.N.
      • Benchimol E.I.
      Risk of surgery and mortality in elderly-onset inflammatory bowel disease: a population-based cohort study.
      • Niewiadomski O.
      • Studd C.
      • Hair C.
      • et al.
      Prospective population-based cohort of inflammatory bowel disease in the biologics era: disease course and predictors of severity.
      • Nordenvall C.
      • Rosvall O.
      • Bottai M.
      • et al.
      Surgical treatment in childhood-onset inflammatory bowel disease-a nationwide register-based study of 4695 incident patients in Sweden 2002-2014.
      • O'Keefe E.A.
      • Wright J.P.
      • Froggatt J.
      • et al.
      Medium-term follow-up of ulcerative colitis in Cape Town.
      • Parragi L.
      • Fournier N.
      • Zeitz J.
      • et al.
      Colectomy rates in ulcerative colitis are low and decreasing: 10-year follow-up data from the Swiss IBD cohort study.
      • Probert C.S.J.
      • Bhakta P.
      • Wicks T.C.B.
      • et al.
      How necessary is colectomy? An epidemiological study of the surgical management of ulcerative colitis amongst different ethnic groups in Leicestershire.
      • Ronnblom A.
      • Holmstrom T.
      • Tanghoj H.
      • et al.
      Low colectomy rate five years after diagnosis of ulcerative colitis. Results from a prospective population-based cohort in Sweden (ICURE) diagnosed during 2005-2009.
      • Samuel S.
      • Ingle S.B.
      • Dhillon S.
      • et al.
      Cumulative incidence and risk factors for hospitalization and surgery in a population-based cohort of ulcerative colitis.
      • Solberg I.C.
      • Lygren I.
      • Jahnsen J.
      • et al.
      Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN study).
      • Spizzo P.
      • Hair C.
      • Beswick L.
      • et al.
      A combined cohort IBD natural history study: high rates of immunomodulator and biologic use, low rates of intestinal surgery for Crohn's disease.
      • Targownik L.E.
      • Singh H.
      • Nugent Z.
      • et al.
      The epidemiology of colectomy in ulcerative colitis: results from a population-based cohort.
      These studies included patients diagnosed between 1962 and 2016, with sample sizes ranging from 41 to 35,782 patients with UC; the largest study was a Danish nationwide register-based study.
      • Rungoe C.
      • Langholz E.
      • Andersson M.
      • et al.
      Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011.
      Six studies reported only on pediatric-onset UC. Fourteen studies reported data from patients in the biologic era, whereas 13 studies reported on surgical risks in the prebiologic era. Study-level risk of bias assessment showed an unclear risk of bias, specifically for cohort attrition and reasons for loss to follow-up evaluation (Supplementary Table 2).
      Table 1Characteristics of Included Studies on Colectomy Risk in Ulcerative Colitis
      StudyCountryData sourceStudy span, ySample sizeAge groupSex (%)Disease extent (%)Time intervals reported, y
      Benchimol et al,
      • Benchimol E.
      • Guttmann A.
      • To T.
      • et al.
      Changes in surgical and hospitalization rates in pediatric inflammatory bowel disease in Ontario, Canada (1994-2007).
      2010
      CanadaOntario Province1994–2004Pediatric3
      Charpentier et al,
      • Charpentier C.
      • Salleron J.
      • Savoye G.
      • et al.
      Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study.
      2014
      FranceEPIMAD1988–2006474ElderlyM (62), F (38)E1 (29), E2 (45), E3 (26)1, 5, and 10
      Chhaya et al,
      • Chhaya V.
      • Saxena S.
      • Cecil E.
      • et al.
      The impact of timing and duration of thiopurine treatment on colectomy in ulcerative colitis: a national population-based study of incident cases between 1989-2009.
      2015
      United KingdomCPRD1989–20098673All agesM (52), F (48)1, 5, and 10
      Chow et al,
      • Chow D.K.
      • Leong R.W.
      • Tsoi K.K.
      • et al.
      Long-term follow-up of ulcerative colitis in the Chinese population.
      2009
      ChinaPrince of Wales Hospital1985–2006172All agesM (52), F (48)E1 (28), E2 (30), E3 (42)1 and 10
      Eriksson et al,
      • Eriksson C.
      • Cao Y.
      • Rundquist S.
      • et al.
      Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Orebro, Sweden, 1963-2010.
      2017
      SwedenOrebro University Hospital1963–2005835All ages10
      Gheorghe et al,
      • Gheorghe C.
      • Pascu O.
      • Gheorghe L.
      • et al.
      Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study.
      2004
      Romania18 secondary and tertiary centers2002–2003163AdultsM (56), F (44)E1 (22), E2 (54), E3 (24)1
      Gower-Rousseau et al,
      • Gower-Rousseau C.
      • Sarter H.
      • Turck D.
      • et al.
      Long-term outcome of paediatric-onset ulcerative colitis: early years are shaping the future.
      2014
      FranceEPIMAD1988–2004159PediatricM (42.1), F (57.9)E1 (25), E2 (38), E3 (37)1, 5, and 10
      Guasch et al,
      • Guasch M.
      • Clos A.
      • Ordas I.
      • et al.
      The availability of anti-TNF agents is associated with reduced early surgical requirements in Crohn's disease but not in ulcerative colitis. A nationwide study from the Eneida registry.
      2018
      SpainENEIDA1995–2000,2007–20128028All ages1 and 5
      Lakatos et al,
      • Lakatos L.
      • Kiss L.S.
      • David G.
      • et al.
      Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002-2006.
      2011
      HungaryVeszprem Province2002–2006220All agesM (56.8), F (43.2)E1 (27), E2 (51), E3 (22)1 and 5
      Langholz et al,
      • Langholz E.
      • Munkholm P.
      • Krasilnikoff P.A.
      • et al.
      Inflammatory bowel diseases with onset in childhood. Clinical features, morbidity, and mortality in a regional cohort.
      1997
      DenmarkCopenhagen1962–198780PediatricM (53), F (47)E1 (25), E2 (43), E3 (29)1, 5, and 10
      Leijonmarck et al,
      • Leijonmarck C.E.
      • Persson P.G.
      • Hellers G.
      Factors affecting colectomy rate in ulcerative colitis: an epidemiologic study.
      1990
      SwedenStockholm County1955–19841586All ages1, 5, and 10
      Lirhus et al,
      • Lirhus S.S.
      • Hoivik M.L.
      • Moum B.
      • et al.
      Regional differences in anti-TNF-alpha therapy and surgery in the treatment of inflammatory bowel disease patients: a Norwegian nationwide cohort study.
      2018
      NorwayNorwegian Patient Registry2010–20125428All agesM (52.8), F (47.2)3
      Lund et al,
      • Lund K.
      • Larsen M.D.
      • Knudsen T.
      • et al.
      Anti-TNF-alpha therapy, use of corticosteroids, and colectomy among paediatric and adolescent patients with ulcerative colitis: a nationwide study.
      2019
      DenmarkDNPR1977–20164449Pediatric5
      Malaty et al,
      • Malaty H.M.
      • Abraham B.P.
      • Mehta S.
      • et al.
      The natural history of ulcerative colitis in a pediatric population: a follow-up population-based cohort study.
      2013
      United StatesSingle Pediatric Center1989–2003112PediatricM (45), F (55)E1 (25), E2 (40), E3 (35)1 and 5
      Nguyen et al,
      • Nguyen G.C.
      • Bernstein C.N.
      • Benchimol E.I.
      Risk of surgery and mortality in elderly-onset inflammatory bowel disease: a population-based cohort study.
      2017
      CanadaOntario Province1999–200812233AdultM (48.7), F (51.3)5 and 10
      Niewiadomski et al,
      • Niewiadomski O.
      • Studd C.
      • Hair C.
      • et al.
      Prospective population-based cohort of inflammatory bowel disease in the biologics era: disease course and predictors of severity.
      2015
      AustraliaBarwon area2007–2008, 2010–201396All ages1 and 5
      Nordenvall et al,
      • Nordenvall C.
      • Rosvall O.
      • Bottai M.
      • et al.
      Surgical treatment in childhood-onset inflammatory bowel disease-a nationwide register-based study of 4695 incident patients in Sweden 2002-2014.
      2018
      SwedenSwedish Patient Register2002–20142295PediatricM (54), F (46)3
      O’Keefe et al,
      • O'Keefe E.A.
      • Wright J.P.
      • Froggatt J.
      • et al.
      Medium-term follow-up of ulcerative colitis in Cape Town.
      1989a
      South AfricaCape Town1970–197991 (5 y), 61 (10 y)All ages5 and 10
      Parragi et al,
      • Parragi L.
      • Fournier N.
      • Zeitz J.
      • et al.
      Colectomy rates in ulcerative colitis are low and decreasing: 10-year follow-up data from the Swiss IBD cohort study.
      2018
      SwitzerlandSIBDCS2006–20151245All agesM (54.6), F (45.4)E1 (20), E2 (32), E3 (38)5 and 10
      Probert et al,
      • Probert C.S.J.
      • Bhakta P.
      • Wicks T.C.B.
      • et al.
      How necessary is colectomy? An epidemiological study of the surgical management of ulcerative colitis amongst different ethnic groups in Leicestershire.
      1993
      EnglandLeicestershire1972–1989691All ages5 and 10
      Ronnblom et al,
      • Ronnblom A.
      • Holmstrom T.
      • Tanghoj H.
      • et al.
      Low colectomy rate five years after diagnosis of ulcerative colitis. Results from a prospective population-based cohort in Sweden (ICURE) diagnosed during 2005-2009.
      2016
      SwedenUppsala health care region2005–2009524All agesM (55.2), F (44.8)E1 (32), E2 (31), E3 (31)1 and 5
      Rungoe et al,
      • Rungoe C.
      • Langholz E.
      • Andersson M.
      • et al.
      Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011.
      2014
      DenmarkDNPR1979–201135,782All agesM (47), F (53)1, 5, and 9
      Samuel et al,
      • Samuel S.
      • Ingle S.B.
      • Dhillon S.
      • et al.
      Cumulative incidence and risk factors for hospitalization and surgery in a population-based cohort of ulcerative colitis.
      2013
      United StatesOlmsted County1970–2004369All agesM (58), F (42)E1 (29), E2 (37), E3 (32)1, 5, and 10
      Solberg et al,
      • Solberg I.C.
      • Lygren I.
      • Jahnsen J.
      • et al.
      Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN study).
      2009
      NorwayIBSEN1990–1993519All agesM (51.4), F (48.6)E1 (33), E2 (35), E3 (32)1, 5, and 10
      Spizzo et al,
      • Spizzo P.
      • Hair C.
      • Beswick L.
      • et al.
      A combined cohort IBD natural history study: high rates of immunomodulator and biologic use, low rates of intestinal surgery for Crohn's disease.
      2016
      AustraliaGECCO2007–201541All ages4
      Targowinik et al,
      • Targownik L.E.
      • Singh H.
      • Nugent Z.
      • et al.
      The epidemiology of colectomy in ulcerative colitis: results from a population-based cohort.
      2012
      CanadaUMIBDED1984–20083752All agesM (48), F (52)1, 5, and 10
      CPRD, Clinical Practice Research Datalink; DNPR, Danish National Patient Register; ENEIDA, Estudio Nacional en Enfermedad Inflamatoria intestinal sobre Determinantes genéticos y Ambientales; E1, proctitis; E2, left-sided colitis; E3, pancolitis; F, female; GECCO, Geelong Epidemiologic Crohn's and Colitis Outcomes; IBSEN, Inflammatory Bowel Disease in Sourtheastern Norway; M, male; SIBDCS, Swiss Inflammatory Bowel Disease Cohort Study; UMIBDED, University of Manitoba Inflammatory Bowel Disease Epidemiologic Database.
      On meta-analysis, the cumulative risk of colectomy at 1, 5, and 10 years after diagnosis was 4.0% (95% CI, 3.3–5.0), 8.8% (95% CI, 7.7–10.0), and 13.3% (95% CI, 11.3–15.5), respectively, with considerable heterogeneity (I
      • Coward S.
      • Clement F.
      • Benchimol E.I.
      • et al.
      Past and future burden of inflammatory bowel diseases based on modeling of population-based data.
       = 95%–98%) (Figure 1A–C). A time-trend, mixed-effects, meta-regression showed a progressive decrease in the 1-, 5-, and 10-year risk of colectomy (P < .01). In contemporary cohorts of patients diagnosed with UC in the 21st century, the cumulative risk of colectomy at 1, 5, and 10 years after diagnosis was 2.8% (95% CI, 2.0–3.9; 42% lower than in patients diagnosed in prior decades; P = .01), 7.0% (95% CI, 5.7–8.6; 26% lower than in patients diagnosed in prior decades, P = .04), and 9.6% (95% CI, 6.3–14.2; 37% lower than in patients diagnosed in prior decades, P = .04), respectively (Supplementary Figure 2).
      Figure thumbnail gr1ab
      Figure 1Cumulative risk of colectomy in patients with ulcerative colitis by (A) 1 year, (B) 5 years, and (C) 10 years after diagnosis. Studies are arranged in order of midyear of cohort recruitment.
      Figure thumbnail gr1c
      Figure 1Cumulative risk of colectomy in patients with ulcerative colitis by (A) 1 year, (B) 5 years, and (C) 10 years after diagnosis. Studies are arranged in order of midyear of cohort recruitment.
      On subgroup analyses, no significant differences were observed in the 1-, 5-, and 10-year risk of colectomy based on geographic location (Supplementary Table 3). On meta-regression, study-level sex distribution and disease extent did not affect risk of surgery (Supplementary Table 4). The cumulative risk of the 1-, 5-, and 10-year risk of colectomy in patients with pediatric-onset UC was 5.7% (95% CI, 4.2–7.8), 14.1% (95% CI, 10.0–19.6), and 21.0% (95% CI, 18.8–23.4), respectively. Sensitivity analyses after exclusion of studies published only in abstract form, and the cumulative 10-year risk of surgery after excluding studies with fewer than 5 years of follow-up evaluation, did not significantly change estimates (data not shown).

       Cumulative Risk of First Major Abdominal Surgery in Patients With Crohn’s Disease

      Table 2 details the characteristics of 22 studies in patients with CD reporting on risk of first surgery.
      • Burr N.E.
      • Lord R.
      • Hull M.A.
      • et al.
      Decreasing risk of first and subsequent surgeries in patients with Crohn's disease in England from 1994 through 2013.
      ,
      • Rungoe C.
      • Langholz E.
      • Andersson M.
      • et al.
      Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011.
      ,
      • Charpentier C.
      • Salleron J.
      • Savoye G.
      • et al.
      Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study.
      ,
      • Gheorghe C.
      • Pascu O.
      • Gheorghe L.
      • et al.
      Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study.
      ,
      • Guasch M.
      • Clos A.
      • Ordas I.
      • et al.
      The availability of anti-TNF agents is associated with reduced early surgical requirements in Crohn's disease but not in ulcerative colitis. A nationwide study from the Eneida registry.
      ,
      • Lirhus S.S.
      • Hoivik M.L.
      • Moum B.
      • et al.
      Regional differences in anti-TNF-alpha therapy and surgery in the treatment of inflammatory bowel disease patients: a Norwegian nationwide cohort study.
      ,
      • Nguyen G.C.
      • Bernstein C.N.
      • Benchimol E.I.
      Risk of surgery and mortality in elderly-onset inflammatory bowel disease: a population-based cohort study.
      • Niewiadomski O.
      • Studd C.
      • Hair C.
      • et al.
      Prospective population-based cohort of inflammatory bowel disease in the biologics era: disease course and predictors of severity.
      • Nordenvall C.
      • Rosvall O.
      • Bottai M.
      • et al.
      Surgical treatment in childhood-onset inflammatory bowel disease-a nationwide register-based study of 4695 incident patients in Sweden 2002-2014.
      ,
      • Spizzo P.
      • Hair C.
      • Beswick L.
      • et al.
      A combined cohort IBD natural history study: high rates of immunomodulator and biologic use, low rates of intestinal surgery for Crohn's disease.
      ,
      • Bernell O.
      • Lapidus A.
      • Hellers G.
      Risk factors for surgery and postoperative recurrence in Crohn's disease.
      • Chatu S.
      • Saxena S.
      • Subramanian V.
      • et al.
      The impact of timing and duration of thiopurine treatment on first intestinal resection in Crohn's disease: national UK population-based study 1989-2010.
      • Jeuring S.
      • Van Den Heuvel T.
      • Zeegers M.
      • et al.
      Hospitalisation and surgery risk in Crohn's disease in the biological era - results from the Dutch population-based IBD-SL cohort.
      • Lakatos P.L.
      • Golovics P.A.
      • David G.
      • et al.
      Has there been a change in the natural history of Crohn's disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009.
      • O'Keefe E.A.
      • Wright J.P.
      • Froggatt J.
      • et al.
      Medium-term follow-up of Crohn's disease in Cape Town.
      • Pandey A.
      • Salazar E.
      • Kong C.S.C.
      • et al.
      Risk of major abdominal surgery in an Asian population-based Crohn's disease cohort.
      • Peneau A.
      • Salleron J.
      • Fumery M.
      • et al.
      Long-term outcome of paediatric-onset Crohn's disease: a population-based study.
      • Peyrin-Biroulet L.
      • Harmsen W.S.
      • Tremaine W.J.
      • et al.
      Surgery in a population-based cohort of Crohn's disease from Olmsted County, Minnesota (1970-2004).
      • Rabilloud M.L.
      • Bretagne J.F.
      • Bajeux E.
      • et al.
      Predictive factors of surgery and bowel damage during the course of Crohn's disease: a population-based study.
      • Ramadas A.V.
      • Gunesh S.
      • Thomas G.A.O.
      • et al.
      Natural history of Crohn's disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates.
      • Solberg I.C.
      • Vatn M.H.
      • Hoie O.
      • et al.
      Clinical course in Crohn's disease: results of a Norwegian population-based ten-year follow-up study.
      • Zhulina Y.
      • Udumyan R.
      • Tysk C.
      • et al.
      The changing face of Crohn's disease: a population-based study of the natural history of Crohn's disease in Orebro, Sweden 1963-2005.
      These studies included patients diagnosed between 1955 and 2015, with sample sizes ranging from 53 to 13,185 patients with CD; a large study was a Danish nationwide register-based study.
      • Rungoe C.
      • Langholz E.
      • Andersson M.
      • et al.
      Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011.
      Two studies were conducted exclusively on pediatric-onset CD. Thirteen studies each reported data from patients in the biologic and prebiologic eras.
      Table 2Characteristics of Included Studies on Primary Resection Risk in Crohn’s Disease
      StudyCountryData sourceStudy span, ySample sizeAge groupSex (%)Location at diagnosis (%)Behavior at diagnosis (%)Time intervals reported, y
      Bernell et al,
      • Bernell O.
      • Lapidus A.
      • Hellers G.
      Risk factors for surgery and postoperative recurrence in Crohn's disease.
      2000
      SwedenStockholm County1955–19891936All agesM (47) F (53)1, 5, and 10
      Burr et al,
      • Burr N.E.
      • Lord R.
      • Hull M.A.
      • et al.
      Decreasing risk of first and subsequent surgeries in patients with Crohn's disease in England from 1994 through 2013.
      2019
      United KingdomResearch One1994–20133059All agesM (47) F (53)1, 5, and 10
      Charpentier et al,
      • Charpentier C.
      • Salleron J.
      • Savoye G.
      • et al.
      Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study.
      2014
      FranceEPIMAD1988–2006367ElderlyM (38) F (62)B1 (78), B2 (17), B3 (5)1, 5, and 10
      Chatu et al,
      • Chatu S.
      • Saxena S.
      • Subramanian V.
      • et al.
      The impact of timing and duration of thiopurine treatment on first intestinal resection in Crohn's disease: national UK population-based study 1989-2010.
      2014
      United KingdomCPRD1989–20105640All agesM (42) F (57)5
      Gheorghe et al,
      • Gheorghe C.
      • Pascu O.
      • Gheorghe L.
      • et al.
      Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study.
      2004
      Romania18 secondary and tertiary centers2002–200385AdultsM (57) F (43)L1 (15), L2 (52), L3 (32), L4 (2)1
      Guasch et al,
      • Guasch M.
      • Clos A.
      • Ordas I.
      • et al.
      The availability of anti-TNF agents is associated with reduced early surgical requirements in Crohn's disease but not in ulcerative colitis. A nationwide study from the Eneida registry.
      2018
      SpainENEIDA1990–1995, 2007–20127496All ages1 and 5
      Jeuring et al,
      • Jeuring S.
      • Van Den Heuvel T.
      • Zeegers M.
      • et al.
      Hospitalisation and surgery risk in Crohn's disease in the biological era - results from the Dutch population-based IBD-SL cohort.
      2015
      The NetherlandsIBD-SL1991–20111159All ages1, 5, and 10
      Lakatos et al,
      • Lakatos P.L.
      • Golovics P.A.
      • David G.
      • et al.
      Has there been a change in the natural history of Crohn's disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009.
      2012
      HungaryVeszprem Province1977–2008506All agesM (49.6) F (50.4)L1 (32.8), L2 (36.0), L3 (30.6), L4 (0.6)B1 (56.9), B2 (19.8), B3 (23.3)1, 5, and 10
      Lirhus et al,
      • Lirhus S.S.
      • Hoivik M.L.
      • Moum B.
      • et al.
      Regional differences in anti-TNF-alpha therapy and surgery in the treatment of inflammatory bowel disease patients: a Norwegian nationwide cohort study.
      2018
      NorwayNorwegian Patient Registry2010–20122829All agesM (47.5) F (52.5)3
      Nguyen et al,
      • Nguyen G.C.
      • Bernstein C.N.
      • Benchimol E.I.
      Risk of surgery and mortality in elderly-onset inflammatory bowel disease: a population-based cohort study.
      2017
      CanadaOntario Province1999–20088985AdultM (44.3) F (55.7)5 and 10
      Niewiadomski et al,
      • Niewiadomski O.
      • Studd C.
      • Hair C.
      • et al.
      Prospective population-based cohort of inflammatory bowel disease in the biologics era: disease course and predictors of severity.
      2015
      AustraliaBarwon area2007–2008,

      2010–2013
      146All ages1 and 5
      Nordenvall et al,
      • Nordenvall C.
      • Rosvall O.
      • Bottai M.
      • et al.
      Surgical treatment in childhood-onset inflammatory bowel disease-a nationwide register-based study of 4695 incident patients in Sweden 2002-2014.
      2018
      SwedenSwedish patient register2002–20142174PediatricM (58) F (42)3
      O’Keefe et al,
      • O'Keefe E.A.
      • Wright J.P.
      • Froggatt J.
      • et al.
      Medium-term follow-up of Crohn's disease in Cape Town.
      1989 b
      South AfricaCape Town1970–197972 (5 y),

      53 (10 y)
      All ages5 and 10
      Pandey et al,
      • Pandey A.
      • Salazar E.
      • Kong C.S.C.
      • et al.
      Risk of major abdominal surgery in an Asian population-based Crohn's disease cohort.
      2015
      Singapore8 hospitals1970–2013430All agesM (61.8) F (38.2)L1 (27.7), L2 (27.7), L3 (41.9), L4 (17.9)B1 (78.1), B2 (14.0), B3 (7.9)5 and 10
      Peneau et al,
      • Peneau A.
      • Salleron J.
      • Fumery M.
      • et al.
      Long-term outcome of paediatric-onset Crohn's disease: a population-based study.
      2012
      FranceEPIMAD1988–2004538Pediatric1, 5, and 10
      Peyrin-Biroulet et al,
      • Peyrin-Biroulet L.
      • Harmsen W.S.
      • Tremaine W.J.
      • et al.
      Surgery in a population-based cohort of Crohn's disease from Olmsted County, Minnesota (1970-2004).
      2012
      United StatesOlmsted County1970–2004310All agesM (50.3) F (49.7)L1 (31.2), L2 (33.1), L3 (33.4), L4 (2.3)B1 (81.3), B2 (4.6), B3 (14.1)5 and 10
      Rabilloud et al,
      • Rabilloud M.L.
      • Bretagne J.F.
      • Bajeux E.
      • et al.
      Predictive factors of surgery and bowel damage during the course of Crohn's disease: a population-based study.
      2016
      FranceBrittany area1994–1997272All ages1, 5, and 10
      Ramadas et al,
      • Ramadas A.V.
      • Gunesh S.
      • Thomas G.A.O.
      • et al.
      Natural history of Crohn's disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates.
      2010
      United KingdomCardiff1986–2003341All agesM (38) F (62)1 and 5
      Rungoe et al,
      • Rungoe C.
      • Langholz E.
      • Andersson M.
      • et al.
      Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011.
      2014
      DenmarkDNPR1979–201113,185AdultM (41) F (59)1, 5, and 9
      Solberg et al,
      • Solberg I.C.
      • Vatn M.H.
      • Hoie O.
      • et al.
      Clinical course in Crohn's disease: results of a Norwegian population-based ten-year follow-up study.
      2007
      NorwayIBSEN1990–1993237All agesM (50.2) F (49.8)L1 (27), L2 (48.5), L3 (22.8), L4 (1.7)B1 (62.0), B2 (27.0), B3 (11.0)1, 5, and 10
      Spizzo et al,
      • Spizzo P.
      • Hair C.
      • Beswick L.
      • et al.
      A combined cohort IBD natural history study: high rates of immunomodulator and biologic use, low rates of intestinal surgery for Crohn's disease.
      2016
      AustraliaGECCO2007–201562All ages4
      Zhulina et al,
      • Zhulina Y.
      • Udumyan R.
      • Tysk C.
      • et al.
      The changing face of Crohn's disease: a population-based study of the natural history of Crohn's disease in Orebro, Sweden 1963-2005.
      2016
      SwedenOrebro University Hospital1963–2005472All agesM (47) F (53)L1 (40.5), L2 (33.9), L3 (23.7), L4 (1.7)B1 (63.5), B2 (19.5), B3 (16.7)1 and 5
      B1, inflammatory; B2, fibrostenotic; B3, penetrating; CPRD, Clinical Practice Research Datalink; DNPR, Danish National Patient Register; ENEIDA, Estudio Nacional en Enfermedad Inflamatoria intestinal sobre Determinantes genéticos y Ambientales; F, female; GECCO, Geelong Epidemiologic Crohn's and Colitis Outcome; IBD-SL, Inflammatory Bowel Disease South Limburg; IBSEN, Inflammatory Bowel Disease in Sourtheastern Norway; L1, ileal; L2, colonic; L3, ileocolonic; L4, upper gastrointestinal tract; M, male.
      On meta-analysis, the cumulative risk of first major abdominal surgery at 1, 5, and 10 years after diagnosis was 18.7% (95% CI, 15.0–23.0), 28.0% (95% CI, 24.0–32.4), and 39.5% (95% CI, 33.3–46.2), respectively, with considerable heterogeneity (I
      • Coward S.
      • Clement F.
      • Benchimol E.I.
      • et al.
      Past and future burden of inflammatory bowel diseases based on modeling of population-based data.
       = 95%–98%) (Figure 2). A time-trend, mixed-effects, meta-regression showed a progressive decrease in the 1-, 5-, and 10-year risk of first major abdominal surgery (P < .001). In contemporary cohorts of patients diagnosed with CD in the 21st century, the cumulative risk of first major abdominal surgery at 1, 5, and 10 years after diagnosis was 12.3% (95% CI, 10.8%–14.0%; 48% lower than in patients diagnosed in prior decades, P < .01), 18.0% (95% CI, 15.4%–21.0%; 50% lower than in patients diagnosed in prior decades, P < .01), and 26.2% (95% CI, 23.4%–29.4%; 44% lower than in patients diagnosed in prior decades, P < .01), respectively (Supplementary Figure 3).
      Figure thumbnail gr2ab
      Figure 2Cumulative risk of major abdominal surgery in patients with Crohn’s disease by (A) 1 year, (B) 5 years, and (C) 10 years after diagnosis. Studies are arranged in order of midyear of cohort recruitment.
      Figure thumbnail gr2c
      Figure 2Cumulative risk of major abdominal surgery in patients with Crohn’s disease by (A) 1 year, (B) 5 years, and (C) 10 years after diagnosis. Studies are arranged in order of midyear of cohort recruitment.
      On subgroup analyses, no significant differences were observed in the 1-, 5-, and 10-year risk of major abdominal surgery based on geographic location (Supplementary Table 3). On meta-regression, study-level sex distribution, disease extent, and behavior did not affect risk of surgery, except for a higher 1-year risk of surgery in studies with a higher proportion of patients with ileum-dominant CD (Supplementary Table 4). The cumulative risk of 1-, 5-, and 10-year risks of major abdominal surgery in patients with pediatric-onset CD was 8.9% (95% CI, 6.8–11.6), 15.5% (95% CI, 3.0–52.2), and 44.1% (95% CI, 39.9–48.3), respectively. Sensitivity analyses after exclusion of studies published only in abstract form, and the cumulative 10-year risk of surgery after excluding studies with fewer than 5 years of follow-up evaluation, did not significantly change estimates (data not shown).

       Cumulative Risk of Re-resection in Patients With Crohn’s Disease With Prior Surgery

      Supplementary Table 5 details the characteristics of 8 studies in patients with CD with prior resection, reporting on risk of re-resection.
      • Burr N.E.
      • Lord R.
      • Hull M.A.
      • et al.
      Decreasing risk of first and subsequent surgeries in patients with Crohn's disease in England from 1994 through 2013.
      ,
      • Shinagawa T.
      • Hata K.
      • Ikeuchi H.
      • et al.
      Rate of reoperation decreased significantly after year 2002 in patients with Crohn's disease.
      ,
      • O'Keefe E.A.
      • Wright J.P.
      • Froggatt J.
      • et al.
      Medium-term follow-up of Crohn's disease in Cape Town.
      ,
      • Beelen E.M.J.
      • van der Woude C.J.
      • Pierik M.J.
      • et al.
      Decreasing trends in intestinal resection and re-resection in Crohn's disease: a nationwide cohort study.
      • Benchimol E.
      • Boualit M.
      • Wong J.
      • et al.
      Predictors of the need for second intestinal resection in children with Crohn's disease.
      • Boualit M.
      • Salleron J.
      • Turck D.
      • et al.
      Long-term outcome after first intestinal resection in pediatric-onset Crohn's disease: a population-based study.
      • Nguyen G.C.
      • Saibil F.
      • Steinhart A.H.
      • et al.
      Postoperative health-care utilization in Crohn's disease: the impact of specialist care.
      • Vester-Andersen M.K.
      • Vind I.
      • Prosberg M.V.
      • et al.
      Hospitalisation, surgical and medical recurrence rates in inflammatory bowel disease 2003-2011-a Danish population-based cohort study.
      These studies included patients diagnosed between 1982 and 2016, with sample sizes ranging from 130 to 8172 patients with CD with prior resection. Two studies were conducted exclusively in pediatric-onset CD. Three studies each reported data from patients in the biologic and prebiologic eras.
      On meta-analysis, the cumulative risk of re-resection at 5 and 10 years after the first resection was 17.7% (95% CI, 13.5–22.9) and 31.3% (95% CI, 24.1–39.6), respectively, with considerable heterogeneity (I2 = 97%–98%) (Figure 3). A time-trend, mixed-effects, meta-regression did not show a significant decrease in the risk of re-resection (5- and 10-year re-resection, P = .21 and P = .16, respectively). In contemporary cohorts of patients diagnosed with CD in the 21st century, the cumulative risk of re-resection in patients with CD with a prior resection 5 and 10 years after diagnosis was 14.8% (95% CI, 11.0–19.7) and 25.5% (95% CI, 11.9–46.6), respectively. The cumulative risk of re-resection in patients with pediatric-onset CD with prior resection at 5 and 10 years after diagnosis was 21.4% (95% CI, 14.5–30.4) and 33.6% (95% CI, 27.5–40.2), respectively.
      Figure thumbnail gr3
      Figure 3Cumulative risk of re-resection in patients with Crohn’s disease with prior surgery by (A) 5 years and (B) 10 years after first surgery. Studies are arranged in order of midyear of cohort recruitment.
      Because of considerable heterogeneity for all analyses, a statistical assessment of publication bias was not performed.

      Discussion

      In this systematic review of 44 population-based cohort studies, we estimated the cumulative risk of surgery in patients with UC and CD and observed that the short- and long-term risk of surgery was 25% to 50% lower in patients diagnosed with IBD in the past 2 decades than prior decades. In contrast to prior estimates, the contemporary 5-year risk of major abdominal surgery was 7.0% in UC and 17.8% in CD in the 21st century. These risks were comparable in patients in North America and Europe; contemporary data from other parts of the world are evolving. Overall, these findings confirm decreasing trends in risk of surgery, which may be related to the disease-modifying effect of a contemporary management approach in patients with IBD.
      Our systematic review updates a prior comprehensive review on risk of surgery in patients with IBD that was published in 2013.
      • Frolkis A.D.
      • Dykeman J.
      • Negron M.E.
      • et al.
      Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies.
      In that review, Frolkis et al
      • Frolkis A.D.
      • Dykeman J.
      • Negron M.E.
      • et al.
      Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies.
      included 30 population-based studies in patients with IBD, largely diagnosed before 2007 and followed up until 2011. The number of cohorts reporting contemporary surgical risk in patients diagnosed after 2000 was very small: 3 and 0 cohorts reporting 5- and 10-year risks of surgery in UC, and 2 and 0 cohorts reporting 5- and 10-year risks of surgery in CD. They inferred a progressively lower 5-year risk of surgery in patients with CD, but not UC, over 5 decades. They speculated that a lower burden of surgery would be observed for patients diagnosed with IBD in the 21st century, but could not provide reliable estimates of contemporary surgical risks owing to a paucity of studies. With an updated literature search, based on 13 and 12 cohorts of patients with UC and CD, respectively, diagnosed after 2000, we have observed significantly lower 5- and 10-year risks of major abdominal surgery in patients diagnosed at the beginning of the 21st century than those observed in the 20th century.
      Several population-based studies have attempted to examine surgical trends in IBD over the past decade. However, most studies have examined annual rates of IBD-related surgery among patients with prevalent IBD, rather than evaluating individual patient-level cumulative risks of surgery in incident cases. These studies generally have shown a decrease in annual rates of emergent surgeries in patients with IBD over time. By using administrative claims data from Ontario between 2003 and 2014, Rahman et al
      • Rahman A.
      • Jairath V.
      • Feagan B.G.
      • et al.
      Declining hospitalisation and surgical intervention rates in patients with Crohn's disease: a population-based cohort.
      observed an approximately 40% decrease in resection surgeries in patients with CD between 2003 and 2014, with a corresponding 33% increase in risk of outpatient nonresection surgeries for CD (related to perianal fistulae and stricture dilations) over the same time period. Ma et al
      • Ma C.
      • Moran G.W.
      • Benchimol E.I.
      • et al.
      Surgical rates for Crohn's disease are decreasing: a population-based time trend analysis and validation study.
      similarly observed a 3.5% annual decrease in rates of surgery in patients with CD between 2002 and 2010, driven primarily by a 10.1% annual decrease in rates of emergent surgery, offset by a 3.7% annual increase in rates of elective surgeries. Based on an administrative claims study, Barnes et al
      • Barnes E.L.
      • Herfarth H.H.
      • Kappelman M.
      • et al.
      A significant decrease in the rate of colectomy for ulcerative colitis among commercially insured patients in the United States between 2007-2016.
      observed similar trends in risk of colectomy in patients with UC. They observed a significant 46% decrease in risk of colectomy between 2007 and 2016, with a 4.5-fold increase in use of biologic therapy in the same time period. Kayal et al
      • Kayal M.
      • Saha A.
      • Poojary P.
      • et al.
      Emergent colectomy rates decreased while elective ileal pouch rates were stable over time: a nationwide inpatient sample study.
      observed a 7.4% annual decrease in risk of emergent colectomy in patients with UC, without a significant change in risk of elective ileal pouch–anal anastomosis surgeries. Although these studies are helpful in informing the overall burden of IBD-related surgeries to the health system, they do not provide patient-level risk estimates, which are critical for prognostication for both patient care and development of risk-based treatment algorithms.
      The exact factors at play contributing to a decrease in risk of surgery in patients with IBD are unclear, although the causes likely are multifactorial and merit further assessment. Although a reduction in surgical rates has been associated with a parallel increase in the use of biologic agents, their exact contribution is hard to quantify. Through claims-based analyses in Ontario, Murthy et al
      • Murthy S.K.
      • Begum J.
      • Benchimol E.I.
      • et al.
      Introduction of anti-TNF therapy has not yielded expected declines in hospitalisation and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study.
      determined that introduction of infliximab may not have resulted in a substantial decrease in risk of CD- and UC-related surgeries, despite high market penetration in patients with CD. They attributed these findings to a “misguided use of infliximab in CD patients and underuse of infliximab in UC.”
      • Murthy S.K.
      • Begum J.
      • Benchimol E.I.
      • et al.
      Introduction of anti-TNF therapy has not yielded expected declines in hospitalisation and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study.
      Other factors such as early diagnosis resulting from increased patient and provider awareness and improved diagnostics may allow timely introduction of disease-modifying therapy, decreasing risk of early surgery. Clinical monitoring and algorithmic treatment escalation also have been shown to decrease the risk of surgery and disease-related complications in patients with CD.
      • Colombel J.F.
      • Panaccione R.
      • Bossuyt P.
      • et al.
      Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial.
      ,
      • Khanna R.
      • Bressler B.
      • Levesque B.G.
      • et al.
      Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial.
      The population-wide, patient-level impact evolving treat-to-target strategies remains to be seen and will be better examined in the coming decade when there is penetration into routine clinical practice. Finally, with better disease control, risk of dysplasia in patients with long-standing UC is decreasing; with advanced endoscopic imaging and therapeutic modalities, several neoplastic lesions, which previously warranted colectomy, now are being managed endoscopically, which also likely is contributing to the lower risk of colectomy in patients with UC.
      • Hata K.
      • Anzai H.
      • Ikeuchi H.
      • et al.
      Surveillance colonoscopy for ulcerative colitis-associated colorectal cancer offers better overall survival in real-world surgically resected cases.
      Despite the merits and strengths of our synthesis, there were important limitations. First, considerable heterogeneity was observed in most analyses. However, it is important to note that the implications and interpretation of a statistical measure such as I2 is not the same for studies of incidence and prevalence, as for comparative observational or interventional studies. High statistical heterogeneity often is observed in these analyses and could not be explained despite subgroup and sensitivity analyses, and meta-regression. We tried to minimize conceptual heterogeneity through strict inclusion and exclusion criteria. Other factors including differences in diagnostic evaluation and evolving treatment paradigms and access in different populations may account for unexplained heterogeneity. Second, as noted earlier, we were unable to examine factors that may have contributed to a decrease in the risk of surgery. There was limited information on the use of disease-modifying therapy in these cohorts. Moreover, the potential impact of newer non–tumor necrosis factor–directed biologics, and the practice of cycling through multiple biologics before surgery, could not be assessed in these population-based cohorts. Future individual patient-level syntheses are required to comprehensively understand the multitude of factors that may contribute to decreasing surgical risks. Third, the number of studies examining rates of re-resection in patients with CD was limited, and, hence, time-trend analysis was underpowered. Future studies are needed to quantify the risk of repeat surgery better. Fourth, studies did not distinguish between types of surgery, including emergent and elective surgeries, resection vs nonresection surgeries, and indications for surgery (eg, medically refractory UC vs colorectal neoplasia). Risk of surgery for perianal CD was not well reported. Finally, in pooling cumulative risks, we assumed complete follow-up evaluation of the cohort, which may have biased findings, particularly for 10-year risks of surgery; however, our estimates for long-term risk of surgery were unchanged when limited to studies with more than 5 years of follow-up evaluation. Future studies with individual patient-level syntheses of risks, or alternative statistical approaches such as bootstrapping, may provide more reliable estimates.
      In conclusion, based on a systematic review of 44 population-based cohorts, we provided robust contemporary cumulative risks of first major abdominal surgery in patients with UC and CD (and repeat surgery in patients with CD) diagnosed in the 21st century. The contemporary cumulative 5-year risk of surgery of 7.0% in UC and 17.8% in CD is substantially lower than that observed in patients diagnosed in the 20th century. Factors contributing meaningfully to these decreased risks, and the cost effectiveness of those strategies, merit further evaluation, including the impact of newer biologics and treat-to-target strategies, to promote value-based care.

      Supplementary Methods

       Data Sources and Search Strategy

      A medical librarian (L.J.P.) designed and performed a comprehensive literature search with input from study investigators using various databases (included Ovid Epub, Medline In-Process and Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science) from inception to September 3, 2019. Controlled vocabulary supplemented with keywords was used to search for population-based cohort studies of natural history and outcomes in inflammatory bowel disease. The references of all identified relevant studies, as well as recent Cochrane reviews on the topic, also were reviewed manually to identify any potentially relevant studies. Two study reviewers (L.T., S.S.) independently reviewed each title and abstract of all studies to exclude nonrelevant studies and reviewed full texts of selected studies for inclusion based on predefined selection criteria. Discrepancies in article selection were reviewed by both reviewers together to resolve with discussion, and, if unable to resolve, were resolved by a third reviewer (W.J.S.). Details of the search strategy are reported in Supplementary Table 1. Supplementary Figure 1 shows the schematic diagram of study selection.

       Data Extraction and Risk of Bias Assessment

      Data abstraction was conducted with a standardized electronic form to capture data on study-, patient-, disease-, and treatment-related characteristics. Two reviewers (L.T., S.S.) independently reviewed and abstracted data, with discrepancies resolved by consensus in consultation with a third reviewer (W.J.S.). Risk of bias assessment was adapted for prevalence studies, and focused on identification of appropriate target population, systematic method of data ascertainment, validated criteria for disease diagnosis and major abdominal surgery, complete follow-up evaluation for more than 70% of the cohort, and a description of patients lost to follow-up evaluation.
      • Frolkis A.D.
      • Dykeman J.
      • Negron M.E.
      • et al.
      Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies.
      Risk of bias assessment was performed by 1 reviewer (L.T.), and a random sample was verified by a second reviewer (S.S.).
      Figure thumbnail fx2
      Supplementary Figure 1Study selection flowchart. CD, Crohn’s disease; IBD, inflammatory bowel disease; UC, ulcerative colitis.
      Figure thumbnail fx3
      Supplementary Figure 2(A) One-year, (B) 5-year, and (C) 10-year cumulative risk of colectomy in patients with ulcerative colitis, diagnosed in the 21st century vs the 20th century. IBD, inflammatory bowel disease.
      Figure thumbnail fx3c
      Supplementary Figure 2(A) One-year, (B) 5-year, and (C) 10-year cumulative risk of colectomy in patients with ulcerative colitis, diagnosed in the 21st century vs the 20th century. IBD, inflammatory bowel disease.
      Figure thumbnail fx4
      Supplementary Figure 3(A) One-year, (B) 5-year, and (C) 10-year cumulative risk of major abdominal surgery in patients with Crohn’s disease, diagnosed in the 21st century vs the 20th century.
      Figure thumbnail fx4c
      Supplementary Figure 3(A) One-year, (B) 5-year, and (C) 10-year cumulative risk of major abdominal surgery in patients with Crohn’s disease, diagnosed in the 21st century vs the 20th century.
      Supplementary Table 1Detailed Search Strategy
      NumberSearchesResults
      Ovid
      1exp Inflammatory Bowel Diseases/220,485
      2enteritis/59,505
      3exp Crohn disease/125,513
      4exp ulcerative colitis/103,377
      5("cleron disease" or "colitis ulcerativa" or "colitis ulcerosa" or "crohn disease∗" or "crohns disease∗" or enteritis or "inflammatory bowel disease∗" or "inflammatory enteropath∗" or "morbus crohn" or "mucosal colitis" or "regional enterocolitis" or "ulcerative colitis" or "ulcerative colorectitis" or "ulcerative procto colitis" or "ulcerative proctocolitis" or "ulcerous colitis").ti,ab,hw,kw.320,562
      61 or 2 or 3 or 4 or 5324,798
      7((("population-based" or populationbased or nationwide or "nation-wide" or national) adj7 (study or cohort∗ or studies)) or ((trend or trends or trending) and (cohort∗ or study or studies or analysis) and (population∗ or nationwide or national or retrospectiv∗ or database∗))).ti,ab,hw,kw626,872
      86 and 77585
      9limit 8 to yr="2000 -Current"7237
      10limit 9 to (editorial or erratum or note or addresses or autobiography or bibliography or biography or blogs or comment or dictionary or directory or interactive tutorial or interview or lectures or legal cases or legislation or news or newspaper article or overall or patient education handout or periodical index or portraits or published erratum or video-audio media or webcasts) [Limit not valid in CCTR,CDSR,Embase,Ovid MEDLINE(R),Ovid MEDLINE(R) Daily Update,Ovid MEDLINE(R) In-Process,Ovid MEDLINE(R) Publisher; records were retained]87
      11from 10 keep 11
      12(9 not 10) or 117151
      13limit 12 to yr="2015 -Current"3855
      14remove duplicates from 132940
      1512 not 133296
      16remove duplicates from 152281
      1714 or 165221
      Scopus
      1TITLE-ABS-KEY("cleron disease" or "colitis ulcerativa" or "colitis ulcerosa" or "crohn disease∗" or "crohns disease∗" or enteritis or "inflammatory bowel disease∗" or "inflammatory enteropath∗" or "morbus crohn" or "mucosal colitis" or "regional enterocolitis" or "ulcerative colitis" or "ulcerative colorectitis" or "ulcerative procto colitis" or "ulcerative proctocolitis" or "ulcerous colitis")
      2TITLE-ABS-KEY((("population-based" or populationbased or nationwide or "nation-wide" or national) W/7 (study or cohort∗ or studies)) or ((trend or trends or trending) and (cohort∗ or study or studies or analysis) and (population∗ or nationwide or national or retrospectiv∗ or database∗)))
      3PUBYEAR AFT 1999
      41 and 2 and 3
      5DOCTYPE(ed) OR DOCTYPE(bk) OR DOCTYPE(er) OR DOCTYPE(no) OR DOCTYPE(sh)
      64 and not 5
      7INDEX(embase) OR INDEX(medline) OR PMID(0∗ OR 1∗ OR 2∗ OR 3∗ OR 4∗ OR 5∗ OR 6∗ OR 7∗ OR 8∗ OR 9∗)
      86 and not 7
      NOTE. The database(s) were as follows: Evidence-Based Medicine Reviews - Cochrane Central Register of Controlled Trials July 2019; Evidence-Based Medicine Reviews - Cochrane Database of Systematic Reviews 2005 to August 29, 2019; Embase 1974 to 2019 August 30; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily 1946 to August 30, 2019.
      Supplementary Table 2Risk of Bias Assessment of All Included Studies
      StudyTarget population definedUsed a systematic method of collecting dataUsed validated criteria for disease diagnosisUsed a clear definition of surgeryPatient retention >70%Describes patients lost to follow-up evaluationOther bias
      Beelen et al,
      • Beelen E.M.J.
      • van der Woude C.J.
      • Pierik M.J.
      • et al.
      Decreasing trends in intestinal resection and re-resection in Crohn's disease: a nationwide cohort study.
      2019
      YesYesYesYesNRNRNo
      Benchimol et al,
      • Benchimol E.
      • Guttmann A.
      • To T.
      • et al.
      Changes in surgical and hospitalization rates in pediatric inflammatory bowel disease in Ontario, Canada (1994-2007).
      2010
      YesUnclearYesYesNRNRNo
      Benchimol et al,
      • Benchimol E.
      • Boualit M.
      • Wong J.
      • et al.
      Predictors of the need for second intestinal resection in children with Crohn's disease.
      2011
      YesUnclearYesYesNRNRNo
      Bernell et al,
      • Bernell O.
      • Lapidus A.
      • Hellers G.
      Risk factors for surgery and postoperative recurrence in Crohn's disease.
      2000
      YesYesYesYesYesNRNo
      Boualit et al,
      • Boualit M.
      • Salleron J.
      • Turck D.
      • et al.
      Long-term outcome after first intestinal resection in pediatric-onset Crohn's disease: a population-based study.
      2013
      YesYesYesYesNRNRNo
      Burr et al,
      • Burr N.E.
      • Lord R.
      • Hull M.A.
      • et al.
      Decreasing risk of first and subsequent surgeries in patients with Crohn's disease in England from 1994 through 2013.
      2019
      YesYesYesYesNRNRNo
      Charpentier et al,
      • Charpentier C.
      • Salleron J.
      • Savoye G.
      • et al.
      Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study.
      2014
      YesYesYesYesNRNRNo
      Chatu et al,
      • Chatu S.
      • Saxena S.
      • Subramanian V.
      • et al.
      The impact of timing and duration of thiopurine treatment on first intestinal resection in Crohn's disease: national UK population-based study 1989-2010.
      2014
      YesYesYesYesNRNRNo
      Chhaya et al,
      • Chhaya V.
      • Saxena S.
      • Cecil E.
      • et al.
      The impact of timing and duration of thiopurine treatment on colectomy in ulcerative colitis: a national population-based study of incident cases between 1989-2009.
      2015
      YesYesYesYesNRNRNo
      Chow et al,
      • Chow D.K.
      • Leong R.W.
      • Tsoi K.K.
      • et al.
      Long-term follow-up of ulcerative colitis in the Chinese population.
      2009
      YesYesYesYesYesNRNo
      Eriksson et al,
      • Eriksson C.
      • Cao Y.
      • Rundquist S.
      • et al.
      Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Orebro, Sweden, 1963-2010.
      2017
      YesYesYesYesNRNRNo
      Gheorghe et al,
      • Gheorghe C.
      • Pascu O.
      • Gheorghe L.
      • et al.
      Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study.
      2004
      YesYesYesNoYesNRNo
      Gower-Rousseau et al,
      • Gower-Rousseau C.
      • Sarter H.
      • Turck D.
      • et al.
      Long-term outcome of paediatric-onset ulcerative colitis: early years are shaping the future.
      2014
      YesNRNRNRNRNRNo
      Guasch et al,
      • Guasch M.
      • Clos A.
      • Ordas I.
      • et al.
      The availability of anti-TNF agents is associated with reduced early surgical requirements in Crohn's disease but not in ulcerative colitis. A nationwide study from the Eneida registry.
      2018
      YesYesUnclearNoNRNRNo
      Jeuring et al,
      • Jeuring S.
      • Van Den Heuvel T.
      • Zeegers M.
      • et al.
      Hospitalisation and surgery risk in Crohn's disease in the biological era - results from the Dutch population-based IBD-SL cohort.
      2015
      YesUnclearUnclearNoNRNRNo
      Lakatos et al,
      • Lakatos L.
      • Kiss L.S.
      • David G.
      • et al.
      Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002-2006.
      2011
      YesYesYesYesNRNRNo
      Lakatos et al,
      • Lakatos P.L.
      • Golovics P.A.
      • David G.
      • et al.
      Has there been a change in the natural history of Crohn's disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009.
      2012
      YesYesYesYesNoNRNo
      Langholz et al,
      • Langholz E.
      • Munkholm P.
      • Krasilnikoff P.A.
      • et al.
      Inflammatory bowel diseases with onset in childhood. Clinical features, morbidity, and mortality in a regional cohort.
      1997
      YesYesYesNoNRNRNo
      Leijonmarck et al,
      • Leijonmarck C.E.
      • Persson P.G.
      • Hellers G.
      Factors affecting colectomy rate in ulcerative colitis: an epidemiologic study.
      1990
      YesYesYesYesYesNRNo
      Lirhus et al,
      • Lirhus S.S.
      • Hoivik M.L.
      • Moum B.
      • et al.
      Regional differences in anti-TNF-alpha therapy and surgery in the treatment of inflammatory bowel disease patients: a Norwegian nationwide cohort study.
      2018
      YesYesYesYesNRNRNo
      Lund et al,
      • Lund K.
      • Larsen M.D.
      • Knudsen T.
      • et al.
      Anti-TNF-alpha therapy, use of corticosteroids, and colectomy among paediatric and adolescent patients with ulcerative colitis: a nationwide study.
      2019
      YesUnclearYesYesNRNRNo
      Malaty et al,
      • Malaty H.M.
      • Abraham B.P.
      • Mehta S.
      • et al.
      The natural history of ulcerative colitis in a pediatric population: a follow-up population-based cohort study.
      2013
      YesYesUnclearYesYesNRNo
      Nguyen et al,
      • Nguyen G.C.
      • Saibil F.
      • Steinhart A.H.
      • et al.
      Postoperative health-care utilization in Crohn's disease: the impact of specialist care.
      2012
      YesYesYesYesNRNRNo
      Nguyen et al,
      • Nguyen G.C.
      • Bernstein C.N.
      • Benchimol E.I.
      Risk of surgery and mortality in elderly-onset inflammatory bowel disease: a population-based cohort study.
      2017
      YesYesYesYesNRNRNo
      Niewiadomski et al,
      • Niewiadomski O.
      • Studd C.
      • Hair C.
      • et al.
      Prospective population-based cohort of inflammatory bowel disease in the biologics era: disease course and predictors of severity.
      2015
      YesUnclearUnclearYesNRNRNo
      Nordenvall et al,
      • Nordenvall C.
      • Rosvall O.
      • Bottai M.
      • et al.
      Surgical treatment in childhood-onset inflammatory bowel disease-a nationwide register-based study of 4695 incident patients in Sweden 2002-2014.
      2018
      YesYesYesYesYesNRNo
      O’Keefe et al,
      • O'Keefe E.A.
      • Wright J.P.
      • Froggatt J.
      • et al.
      Medium-term follow-up of ulcerative colitis in Cape Town.
      1989
      Article on ulcerative colitis.
      YesUnclearYesYesYesNRNo
      O’Keefe et al,
      • O'Keefe E.A.
      • Wright J.P.
      • Froggatt J.
      • et al.
      Medium-term follow-up of Crohn's disease in Cape Town.
      1989
      Article on Crohn’s disease.
      YesUnclearYesYesYesNRNo
      Pandey et al,
      • Pandey A.
      • Salazar E.
      • Kong C.S.C.
      • et al.
      Risk of major abdominal surgery in an Asian population-based Crohn's disease cohort.
      2015
      YesYesYesYesNRNRNo
      Parragi et al,
      • Parragi L.
      • Fournier N.
      • Zeitz J.
      • et al.
      Colectomy rates in ulcerative colitis are low and decreasing: 10-year follow-up data from the Swiss IBD cohort study.
      2018
      YesYesYesYesNRNRNo
      Peneau et al,
      • Peneau A.
      • Salleron J.
      • Fumery M.
      • et al.
      Long-term outcome of paediatric-onset Crohn's disease: a population-based study.
      2012
      YesUnclearUnclearYesNRNRNo
      Peyrin-Biroulet et al,
      • Peyrin-Biroulet L.
      • Harmsen W.S.
      • Tremaine W.J.
      • et al.
      Surgery in a population-based cohort of Crohn's disease from Olmsted County, Minnesota (1970-2004).
      2012
      YesYesYesYesYesNRNo
      Probert et al,
      • Probert C.S.J.
      • Bhakta P.
      • Wicks T.C.B.
      • et al.
      How necessary is colectomy? An epidemiological study of the surgical management of ulcerative colitis amongst different ethnic groups in Leicestershire.
      1993
      YesYesNRYesYesNRNo
      Rabilloud et al,
      • Rabilloud M.L.
      • Bretagne J.F.
      • Bajeux E.
      • et al.
      Predictive factors of surgery and bowel damage during the course of Crohn's disease: a population-based study.
      2016
      YesUnclearYesNoNRNRNo
      Ramadas et al,
      • Ramadas A.V.
      • Gunesh S.
      • Thomas G.A.O.
      • et al.
      Natural history of Crohn's disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates.
      2010
      YesYesYesYesYesNRNo
      Ronnblom et al,
      • Ronnblom A.
      • Holmstrom T.
      • Tanghoj H.
      • et al.
      Low colectomy rate five years after diagnosis of ulcerative colitis. Results from a prospective population-based cohort in Sweden (ICURE) diagnosed during 2005-2009.
      2016
      YesYesYesYesYesYesNo
      Rungoe et al,
      • Rungoe C.
      • Langholz E.
      • Andersson M.
      • et al.
      Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011.
      2014
      YesYesYesYesNRNRNo
      Samuel et al,
      • Samuel S.
      • Ingle S.B.
      • Dhillon S.
      • et al.
      Cumulative incidence and risk factors for hospitalization and surgery in a population-based cohort of ulcerative colitis.
      2013
      YesYesYesYesNRNRNo
      Shinagawa et al,
      • Shinagawa T.
      • Hata K.
      • Ikeuchi H.
      • et al.
      Rate of reoperation decreased significantly after year 2002 in patients with Crohn's disease.
      2019
      YesYesYesYesNRNRNo
      Solberg et al,
      • Solberg I.C.
      • Vatn M.H.
      • Hoie O.
      • et al.
      Clinical course in Crohn's disease: results of a Norwegian population-based ten-year follow-up study.
      2007
      YesYesYesYesYesYesNo
      Solberg et al,
      • Solberg I.C.
      • Lygren I.
      • Jahnsen J.
      • et al.
      Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN study).
      2009
      YesYesYesYesYesYesNo
      Spizzo et al,
      • Spizzo P.
      • Hair C.
      • Beswick L.
      • et al.
      A combined cohort IBD natural history study: high rates of immunomodulator and biologic use, low rates of intestinal surgery for Crohn's disease.
      2016
      YesUnclearUnclearNoNRNRNo
      Targownik et al,
      • Targownik L.E.
      • Singh H.
      • Nugent Z.
      • et al.
      The epidemiology of colectomy in ulcerative colitis: results from a population-based cohort.
      2012
      YesYesYesYesNRNRNo
      Vester-Andersen et al,
      • Vester-Andersen M.K.
      • Vind I.
      • Prosberg M.V.
      • et al.
      Hospitalisation, surgical and medical recurrence rates in inflammatory bowel disease 2003-2011-a Danish population-based cohort study.
      2014
      YesYesYesYesYesNRNo
      Zhulina et al,
      • Zhulina Y.
      • Udumyan R.
      • Tysk C.
      • et al.
      The changing face of Crohn's disease: a population-based study of the natural history of Crohn's disease in Orebro, Sweden 1963-2005.
      2016
      YesYesYesYesYesNRNo
      NR, not reported.
      a Article on ulcerative colitis.
      b Article on Crohn’s disease.
      Supplementary Table 3Subgroup Analysis: Difference in 1-, 5-, and 10-Year Risk of Surgery in Patients With Ulcerative Colitis and Crohn’s Disease, Based on Geographic Location
      Location1-year risk5-year risk10-year riskDifference between groups
      Ulcerative colitis
       Europe4.0% (95% CI, 3.0–5.3)8.0% (95% CI, 6.7–9.6)12.9% (95% CI, 10.5–15.9)1-year risk: P = .31
       North America4.3% (95% CI, 3.3–5.6)10.7% (95% CI, 8.6–13.1)14.0% (95% CI, 11.4–17.2)5-year risk: P = .12
       Others2.2% (95% CI, 1.0–4.9)7.7% (95% CI, 4.3–13.6)13.5% (95% CI, 4.2–35.6)10-year risk: P = .86
      Crohn’s disease, first surgery
       Europe18.6% (95% CI, 14.8–23.1)27.2% (95% CI, 22.3–32.6)38.6% (95% CI, 30.2–47.7)1-year risk: P = .13
       North America32.7% (95% CI, 23.0–44.2)42.7% (95% CI, 28.4–58.3)5-year risk: P = .56
       Others13.0% (95% CI, 8.5–19.5)25.2% (95% CI, 16.2–36.9)47.5% (95% CI, 15.2–82.1)10-year risk: P = .84
      Supplementary Table 4Meta-Regression: P Values for Differences in 1-, 5-, and 10-Year Risk of Surgery in Patients With Ulcerative Colitis and CD, Based on Study-Level Factors Using Mixed-Effects Meta-Regression
      1-year risk of surgery5-year risk of surgery10-year risk of surgery
      Ulcerative colitis
       Proportion of males in cohort.40.26.28
       Proportion of patients with extensive colitis.20.30.44
      Crohn’s disease
       Proportion of males in cohort.30.37.84
       Proportion of patients with ileum-dominant CD (ileal or ileocolonic CD).08.81.86
       Proportion of patients with penetrating or stricturing behavior.68.78.93
      CD, Crohn’s disease.
      Supplementary Table 5Characteristics of Included Studies on Re-resection Risk in Crohn’s Disease
      StudyCountryData sourceStudy span, ySample size, with prior surgeryAge groupSex (%)Phenotype at diagnosis (%)Behavior at diagnosis (%)Time intervals reported, y
      Beelen et al,
      • Beelen E.M.J.
      • van der Woude C.J.
      • Pierik M.J.
      • et al.
      Decreasing trends in intestinal resection and re-resection in Crohn's disease: a nationwide cohort study.
      2019
      The NetherlandsPALGA1991–20158172All agesM (40) F (60)5 and 10
      Benchimol et al,
      • Benchimol E.
      • Boualit M.
      • Wong J.
      • et al.
      Predictors of the need for second intestinal resection in children with Crohn's disease.
      2011
      CanadaOntario Crohn’s and Colitis Cohort1994–2007553Pediatric2, 5, and 10
      Boualit et al,
      • Boualit M.
      • Salleron J.
      • Turck D.
      • et al.
      Long-term outcome after first intestinal resection in pediatric-onset Crohn's disease: a population-based study.
      2013
      FranceEPIMAD1988–2004130PediatricM (45) F (55)L1 (19), L2 (10), L3 (71), L4 (20)B1 (45), B2 (45), B3 (10)2, 5, and 10
      Burr et al,
      • Burr N.E.
      • Lord R.
      • Hull M.A.
      • et al.
      Decreasing risk of first and subsequent surgeries in patients with Crohn's disease in England from 1994 through 2013.
      2019
      United KingdomResearch One1994–20133059All agesM (47) F (53)1, 5, and 10
      Nguyen et al,
      • Nguyen G.C.
      • Saibil F.
      • Steinhart A.H.
      • et al.
      Postoperative health-care utilization in Crohn's disease: the impact of specialist care.
      2012
      CanadaOntario Province1996–20092943All agesM (45) F (55)2, 5, and 10
      O’Keefe et al,
      • O'Keefe E.A.
      • Wright J.P.
      • Froggatt J.
      • et al.
      Medium-term follow-up of Crohn's disease in Cape Town.
      1989
      South AfricaCape Town1970–197931All ages5 and 10
      Shinagawa et al,
      • Shinagawa T.
      • Hata K.
      • Ikeuchi H.
      • et al.
      Rate of reoperation decreased significantly after year 2002 in patients with Crohn's disease.
      2019
      JapanRGIBD1982–20161871All agesM (72.6) F (27.4)L1 (31.4), L2 (8.9), L3 (59.8)B1/B2 (54.0), B3 (46.0)5 and 10
      Vester-Andersen et al,
      • Vester-Andersen M.K.
      • Vind I.
      • Prosberg M.V.
      • et al.
      Hospitalisation, surgical and medical recurrence rates in inflammatory bowel disease 2003-2011-a Danish population-based cohort study.
      2014
      DenmarkCopenhagen County and City, Frederiksberg City2003–2004213All agesM (46.5) F (53.5)L1 (26.7), L2 (41.3), L3 (23.5), L4 (8.5)B1 (77.9), B2 (9.4), B3 (12.7)1, 5, and 7
      B1, inflammatory; B2, fibrostenotic; B3, penetrating; F, female; L1, ileal; L2, colonic; L3, ileocolonic; L4, upper gastrointestinal tract; M, male; PALGA, Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief; RGIBD, Research Group for Intractable Inflammatory Bowel Disease of the Ministry of Health, Labour and Welfare of Japan.

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