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3.
Cancer Epidemiol Biomarkers Prev ; 30(5): 886-894, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33627380

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) has been associated with hepatobiliary cancer, but existing evidence is poor. We evaluated risk of death from hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC) among patients with IBD. METHODS: This Swedish/Danish population-based cohort study (1969-2017) followed patients with IBD and 1:10 matched population comparators from their diagnosis/match date until death, emigration, or end of follow-up. RESULTS: Among the 97,496 patients with ulcerative colitis/963,026 comparators, we found 66/390 HCC-deaths, 120/173 ICC-deaths, and 91/220 ECC-deaths (median follow-up 10 years); the 10-year-mortality was 0.5‰ (per mille) for HCC, 0.6‰ for ICC, and 0.4‰ for ECC, which decreased to 0.3‰, 0.4‰, and 0.2‰, respectively, in 2003-2017. Overall hazard ratios (HR) were 1.83 [95% confidence interval (CI), 1.41-2.38] for HCC-, 7.33 (95% CI, 5.81-9.25) for ICC-, and 4.46 (95% CI, 3.49-5.70) for ECC-deaths. A total of 22/66 HCC-deaths, 87/120 ICC-deaths, and 55/91 ECC-deaths occurred among patients with ulcerative colitis with primary sclerosing cholangitis (PSC), corresponding to 10-year-mortality of 6.7‰, 26.2‰, and 17.2‰, respectively. Among 47,399 patients with Crohn's disease (median follow-up 11 years), 10-year-mortality from HCC (n = 28), ICC (n = 28), and ECC (n = 24) were 0.3‰, 0.1‰, and 0.3‰, respectively, and corresponding HRs were 1.96 (95% CI, 1.31-2.93), 3.33 (95% CI, 2.19-5.09), and 3.10 (95% CI, 1.97-4.87). One of 28 HCC-deaths, 14/28 ICC-deaths (10-year-mortality 19‰), and 12/24 ECC-deaths (10-year-mortality 14‰) occurred after PSC. CONCLUSIONS: Risk of HCC-, ICC-, and ECC-deaths was low in patients with IBD and decreased over time. However, a large proportion of deaths occurred after PSC. IMPACT: Guidelines on specific surveillance strategies for patients with IBD with PSC, but not those without PSC, are needed.

4.
Scand J Gastroenterol ; 56(4): 410-421, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33632044

RESUMO

BACKGROUND: It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR). METHODS: A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/- one year and within +/- three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005-2008, 2009-2012, and 2013-2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes. RESULTS: Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4-81.7) were ever captured in the PDR/NPR in. A time window of +/- one year or +/- three months reduced the sensitivity to 63.3% (95% CI: 61.3-65.3) and 52.6% (95% CI: 50.5-54.6), respectively. The sensitivity was high (>85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab. CONCLUSIONS: The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG.

7.
Aliment Pharmacol Ther ; 53(4): 471-483, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33340426

RESUMO

BACKGROUND: Comparisons of second-line anti-tumour necrosis factor (TNF) agents and vedolizumab are sparse. AIM: To evaluate the effectiveness of anti-TNF agents compared to vedolizumab as second-line biologics in inflammatory bowel disease (IBD). METHODS: A propensity score-matched cohort was created using Swedish nationwide registers. Patients with Crohn's disease or ulcerative colitis, exposed to first-line anti-TNF treatment, who initiated a second anti-TNF agent or vedolizumab in 2014-2016 (N = 1363) were included. The primary outcome was drug survival at 12 months. Secondarily, we assessed survival without IBD-related hospitalisation, IBD-related surgery, antibiotics, or hospitalisation because of infection, and also corticosteroid exposure. RESULTS: After 1:1 propensity score matching, 400 patients (Crohn's disease, N = 198; ulcerative colitis, N = 202) remained. For Crohn's disease, drug survival was 73% in the vedolizumab group vs 74% in the anti-TNF group (difference: 1 percentage point; 95% confidence interval [CI]:-11-13; P = 0.87). Survival without IBD-related hospitalisation (82% vs 88%), surgery (82% vs 89%), antibiotics (65% vs 71%), hospitalisation due to infection (95% vs 88%) and corticosteroids (58% vs 48%) were not statistically significantly different between groups. For ulcerative colitis, drug survival was 69% in the vedolizumab group vs 62% in the anti-TNF group (difference: -7 percentage points; 95% CI: -20 to 6; P = 0.30). Vedolizumab-treated patients had lower survival without IBD-related hospitalisation (82% vs 93%, P = 0.02). Survival without colectomy (93% vs 97%), antibiotics (81% vs 70%), hospitalisation due to infection (92% vs 92%) and corticosteroids (58% vs 48%) were not statistically significantly different. CONCLUSIONS: Based on Swedish clinical practice, the effectiveness and safety of second-line anti-TNF and vedolizumab at 12 months appeared largely similar.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Preparações Farmacêuticas , Anticorpos Monoclonais Humanizados , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Suécia/epidemiologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/uso terapêutico
8.
J Crohns Colitis ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216873

RESUMO

BACKGROUND: In addition to their potent lipid-lowering action, statins may modulate inflammation. However, data on statin use and the risk of inflammatory bowel diseases (IBD) have been inconsistent. METHODS: We searched the Nationwide Swedish Patient Register (inpatient and non-primary outpatient care) to identify adults diagnosed with Crohn's disease (CD, n=7,637) or ulcerative colitis (UC, n=15,652) from 2006-2014. Each case was matched to 10 general population controls (n=232,890). Data on dispensed statin prescriptions were extracted from the Prescribed Drug Register. Conditional logistic regression models estimated odds ratios (ORs) for risk of IBD according to statin exposure while controlling for potential confounders, including indications for statin therapy. RESULTS: In multivariable adjusted models, compared to no statin use, any statin use was associated with a lower risk of CD (OR=0.71; 95% CI, 0.63-0.79), but not UC (OR=1.03; 95% CI, 0.96-1.11). The lowest OR for CD was seen for current statin use (OR=0.67; 95% CI, 0.60-0.75). For CD, the lowest category of cumulative statin dose (31-325 defined daily dose, DDD) was associated with an OR of 0.73 (95% CI, 0.61-0.88) and the highest category (>1500 DDD) with an OR of 0.66 (95% CI, 0.55-0.80), Ptrend=0.10. For UC, the lowest and highest dose categories yielded ORs of 1.12 (95% CI, 1.00-1.25) and 0.99 (95% CI, 0.88-1.13), respectively, Ptrend=0.13. CONCLUSIONS: Statin use was associated with a lower risk of CD, but not UC. The association with CD risk appeared strongest for current statin use. Our findings suggest that statin use may influence the development of CD.

9.
Clin Epidemiol ; 12: 1059-1072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116900

RESUMO

Background: The Swedish Quality Register for Inflammatory Bowel Disease (SWIBREG) contains clinical data for the study of inflammatory bowel disease (IBD). The Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort was recently established for the study of gastrointestinal histopathology. We aimed to develop and validate a histology score from ESPRESSO using clinical information from SWIBREG, and secondarily, to evaluate the association of the score on IBD-related hospitalization. Methods: In a nationwide, population-based cohort study of patients with IBD during 1969-2017, we linked endoscopic inflammation in SWIBREG with histologic inflammation in ESPRESSO. We established a clinically interpretable model for predicting the endoscopic score from histology using scalable Bayesian rule lists to define a SNOMED-based histology score applicable to the ESPRESSO cohort. We also assessed the impact of baseline endoscopic and histology scores on time to IBD-related hospitalization. Results: We identified 5225 individuals with IBD comprising 11,051 endoscopic assessments in SWIBREG linked to a histopathology record in ESPRESSO. We created predictive models to calculate a SNOMED-based histology score which predicted the endoscopic score. Split-sample validated areas under the ROC curves for the score predicting a non-zero endoscopic score were 0.80 (0.78-0.81) in UC, 0.70 (0.68-0.72) in CD, and 0.76 (0.73-0.78) in IBD-U. In a subset of 2741 individuals with an initial IBD diagnosis and a corresponding record in ESPRESSO with an endoscopic assessment in SWIBREG, the baseline endoscopic and histology scores were associated with time to IBD-related hospitalization (endoscopy log-rank UC p<0.001, CD p=0.020, IBD-U p<0.001; histology log-rank UC p=0.018, CD p=0.960, IBD-U p=0.034). Conclusion: Histopathology data in ESPRESSO accurately predict endoscopic scores in SWIBREG. Baseline endoscopic and histologic scores were associated with time to IBD-related hospitalization, particularly in UC. The SNOMED-based histology score can be used as a measure of disease activity in future register-based IBD studies.

11.
Gut ; 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32474410

RESUMO

OBJECTIVE: Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD). DESIGN: In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969-2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs). RESULTS: We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32). CONCLUSION: SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.

12.
Aliment Pharmacol Ther ; 52(1): 143-154, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32412143

RESUMO

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased risk of cancer. AIM: To assess the risk of pancreatic cancer in IBD compared to the general population. METHODS: Patients with incident IBD 1969-2017 were identified in Danish and Swedish National Patient Registers and through biopsy data, and were matched to IBD-free reference individuals by sex, age, place of residence and year of IBD diagnosis. We linked data to Cancer and Causes of Death Registers and examined the absolute and relative risks of pancreatic cancer and pancreatic cancer death. RESULTS: Among 161 926 patients followed for 2 000 951 person years, 442 (0.27%) were diagnosed with pancreatic cancer compared to 3386 (0.21%) of the 1 599 024 reference individuals. The 20-year cumulative incidence was 0.34% (95% confidence interval 0.30-0.38) vs 0.29% (0.28-0.30). The incidence rate was 22.1 (20.1-24.2)/100 000 person years in the patients (excluding the first year of follow-up: 20.8 [18.8-23.0]), and 16.6 (16.0-17.2) in the reference individuals. The hazard ratio (HR) for pancreatic cancer was increased overall: 1.43 (1.30-1.58), in subtypes (Crohn's disease: 1.44 [1.18-1.74]; ulcerative colitis: 1.35 [1.19-1.53]; IBD unclassified: 1.99 [1.50-2.64]) and especially in IBD patients with primary sclerosing cholangitis: 7.55 (4.94-11.5). Patients and reference individuals with pancreatic cancer did not differ in cancer stage (P = 0.17) or pancreatic cancer mortality (HR 1.07 [0.95-1.21]). CONCLUSIONS: Patients with IBD had an excess risk of pancreatic cancer, in particular patients with primary sclerosing cholangitis. However, the cumulative incidence difference after 20 years was small: 0.05%, that is, one extra pancreatic cancer per 2000 IBD patients.


Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Suécia/epidemiologia , Adulto Jovem
13.
Scand J Gastroenterol ; 55(4): 430-435, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32370571

RESUMO

Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown.Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals.Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96-99)% for Crohn's disease, 98 (97-100)% for ulcerative colitis, and 8 (4-11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32-40)% for colonic Crohn's disease (L2), 61 (56-65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78-87)% for perianal disease. Correspondingly, the PPV was 80 (71-89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis.Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients.

14.
Aliment Pharmacol Ther ; 51(11): 1022-1030, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32319125

RESUMO

BACKGROUND: The vagus nerve provides essential parasympathetic innervation to the gastrointestinal system and is known to have anti-inflammatory properties. AIMS: To explore the relationship between vagotomy and the risk of inflammatory bowel disease (IBD) and its major categories: Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A matched cohort comprising 15 637 patients undergoing vagotomy was identified through the Swedish Patient Register from 1964 to 2010. Each vagotomised patient was matched for birth year and gender with 40 nonvagotomised individuals on the date of vagotomy. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for IBD using flexible parametric models adjusted for matching variables, year of vagotomy, birth country, chronic obstructive pulmonary disease and comorbidity index. RESULTS: We observed 119 (0.8%) patients with vagotomy developed IBD compared to 3377 (0.5%) IBD cases in nonvagotomised individuals. The crude incidence of IBD (per 1000 person-years) was 0.38 for vagotomised patients and 0.25 for nonvagotomised individuals. We observed a time-dependent elevated risk of IBD associated with vagotomy, for instance, the HR (95% CI) was 1.80 (1.40-2.31) at year 5 and 1.49 (1.14-1.96) at year 10 post-vagotomy. The association appeared to be stronger for truncal than selective vagotomy and limited to CD (HR was 3.63 [1.94-6.80] for truncal and 2.06 [1.49-2.84] for selective vagotomy) but not UC (1.36 [0.71-2.62] for truncal and 1.25 [0.95-1.63] for selective vagotomy). CONCLUSIONS: We found a positive association between vagotomy and later IBD, particularly for CD. The finding indirectly underlines the beneficial role of the vagal tone in IBD.


Assuntos
Doenças Inflamatórias Intestinais/etiologia , Complicações Pós-Operatórias/etiologia , Vagotomia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/etiologia , Doença de Crohn/epidemiologia , Doença de Crohn/etiologia , Feminino , Humanos , Incidência , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros , Fatores de Risco , Suécia/epidemiologia , Vagotomia/estatística & dados numéricos
15.
Aliment Pharmacol Ther ; 51(8): 789-800, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32133656

RESUMO

BACKGROUND: Growth retardation is well described in childhood-onset inflammatory bowel disease (IBD). AIMS: To study if childhood-onset IBD is associated with reduced final adult height. METHODS: We identified 4201 individuals diagnosed with childhood-onset IBD 1990-2014 (Crohn's disease: n = 1640; ulcerative colitis: n = 2201 and IBD-unclassified = 360) in the Swedish National Patient Register. RESULTS: Patients with IBD attained a lower adult height compared to reference individuals (adjusted mean height difference [AMHD] -0.9 cm [95% CI -1.1 to -0.7]) and to their healthy siblings (AMHD -0.8 cm [-1.0 to -0.6]). Patients with Crohn's disease (CD) were slightly shorter than patients with ulcerative colitis (UC; -1.3 cm vs -0.6 cm). Lower adult height was more often seen in patients with pre-pubertal disease onset (AMHD -1.6 cm [-2.0 to -1.2]), and in patients with a more severe disease course (AMHD -1.9 cm, [-2.4 to -1.4]). Some 5.0% of CD and 4.3% of UC patients were classified as growth retarded vs 2.5% of matched reference individuals (OR 2.42 [95% CI 1.85-3.17] and 1.74 [1.36-2.22] respectively). CONCLUSION: Patients with childhood-onset IBD on average attain a slightly lower adult height than their healthy peers. Adult height was more reduced in patients with pre-pubertal onset of disease and in those with a more severe disease course.


Assuntos
Estatura , Transtornos do Crescimento/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Adolescente , Adulto , Idade de Início , Estudos de Casos e Controles , Criança , Desenvolvimento Infantil/fisiologia , Estudos de Coortes , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Feminino , Transtornos do Crescimento/complicações , Humanos , Doenças Inflamatórias Intestinais/complicações , Masculino , Sistema de Registros , Suécia/epidemiologia , Adulto Jovem
16.
Clin Epidemiol ; 12: 273-285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210631

RESUMO

Purpose: Patients with Crohn's disease have increased work loss. We aimed to describe changes in work ability in relation to pharmacological and surgical treatments. Patients and Methods: We linked data from the Swedish National Patient Register, The Swedish Quality Register for Inflammatory Bowel Disease SWIBREG, The Prescribed Drug Register, The Longitudinal Integrated Database for Health Insurance and Labour Market Studies, and the Social Insurance Database. We identified working-age (19-59 years) patients with incident Crohn's disease 2006-2013 and population comparator subjects matched by sex, birth year, region, and education level. We assessed the number of lost workdays due to sick leave and disability pension before and after treatments. Results: Of 3956 patients (median age 34 years, 51% women), 39% were treated with aminosalicylates, 52% with immunomodulators, 22% with TNF inhibitors, and 18% with intestinal surgery during a median follow-up of 5.3 years. Most patients had no work loss during the study period (median=0 days). For all treatments, the mean number of lost workdays increased during the months before treatment initiation, peaked during the first month of treatment and decreased thereafter, and was heavily influenced by sociodemographic factors and amount of work loss before first Crohn's disease diagnosis. The mean increase in work loss days compared to pre-therapeutic level was ~3 days during the first month of treatment for all pharmacological therapies and 11 days for intestinal surgery. Three months after treatment initiation, 88% of patients treated surgically and 90-92% of patients treated pharmacologically had the same amount of work loss as before treatment start. Median time to return to work was 2 months for all treatments. Conclusion: In this regular clinical setting, patients treated surgically had more lost workdays than patients treated pharmacologically, but return to work was similar between all treatments.

17.
Epidemiology ; 31(3): 359-364, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32091429

RESUMO

The predictions from an accurate prognostic model can be of great interest to patients and clinicians. When predictions are reported to individuals, they may decide to take action to improve their health or they may simply be comforted by the knowledge. However, if there is a clearly defined space of actions in the clinical context, a formal decision rule based on the prediction has the potential to have a much broader impact. The use of a prediction-based decision rule should be formalized and preferably compared with the standard of care in a randomized trial to assess its clinical utility; however, evidence is needed to motivate such a trial. We outline how observational data can be used to propose a decision rule based on a prognostic prediction model. We then propose a framework for emulating a prediction driven trial to evaluate the clinical utility of a prediction-based decision rule in observational data. A split-sample structure is often feasible and useful to develop the prognostic model, define the decision rule, and evaluate its clinical utility. See video abstract at, http://links.lww.com/EDE/B656.

18.
Lancet Gastroenterol Hepatol ; 5(5): 475-484, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32066530

RESUMO

BACKGROUND: Crohn's disease is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance strategies, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account. Such biases can be accounted for by assessing CRC incidence by tumour stage and CRC mortality by tumour stage. We aimed to assess rates of incident CRC and CRC mortality among patients with Crohn's disease compared with the general population. METHODS: For this nationwide register-based cohort study, we used International Classification of Disease codes in national patient registers and pathology reports to identify incident cases of Crohn's disease. In Denmark we searched for incident cases between January, 1977, and December, 2011, and in Sweden between January, 1969, and December, 2017. For each patient with Crohn's disease, we identified up to ten reference individuals in national population registers and matched them by sex, age, calendar year, and place of residence. Matched reference individuals had to be alive and free of inflammatory bowel disease at the start of follow-up of index patients with Crohn's disease, and stopped contributing to reference person-years if they were diagnosed with inflammatory bowel disease. Our main outcome was death from CRC (main or contributory cause of death) as captured in the cause-of-death registers. Our secondary outcome was incident CRC, as defined by the cancer registers. We used Cox regression to estimate hazard ratios (HRs) for incident CRC and CRC mortality, taking tumour stage into account. We used a series of Cox models to estimate cause-specific HRs of the different competing outcomes (CRC diagnosis, CRC death, and other causes of death) and adjusted for tumour stage at CRC diagnosis. FINDINGS: During the 1969-2017 study period, we identified 47 035 patients with incident Crohn's disease (13 056 in Denmark and 33 979 in Sweden) and 463 187 matched reference individuals. During follow-up, 296 (0·47 per 1000 person-years) CRC deaths occurred among individuals with Crohn's disease compared with 1968 (0·31 per 1000 person-years) in reference individuals, corresponding to an overall adjusted HR of 1·74 (1·54-1·96). 499 (0·82 per 1000 person-years) cases of incident CRC were diagnosed in patients with Crohn's disease compared with 4084 (0·64 per 1000 person-years) cases in reference individuals, corresponding to an overall adjusted HR of 1·40 (95% CI 1·27-1·53). Patients with Crohn's disease who were diagnosed with CRC were at increased risk of CRC mortality compared with reference individuals also diagnosed with CRC (HR 1·42 [1·16-1·75] when adjusted for tumour stage), and tumour stage at CRC diagnosis did not differ between groups (p=0·27). Patients with Crohn's disease who had follow-up of 8 years or longer or who were diagnosed with primary sclerosing cholangitis (PSC) and hence were potentially eligible for CRC surveillance had an increased overall risk of CRC death (HR 1·40 [1·16-1·68]) or CRC diagnosis (HR 1·12 [0·98-1·28]). However, in patients potentially eligible for CRC surveillance we only found significantly increased risks in patients diagnosed with Crohn's disease before the age of 40 years, patients with disease activity in the colon only, or patients with PSC. INTERPRETATION: Patients with Crohn's disease are at increased risk of CRC diagnosis and CRC death. Patients with Crohn's disease who have CRC have a higher mortality than patients without Crohn's disease who are also diagnosed with CRC. CRC surveillance should likely be focused on patients diagnosed with Crohn's disease before the age of 40 years, on patients with colon inflammation, and on those who have PSC. FUNDING: Swedish Medical Society, Karolinska Institutet, Regional Agreement on Medical Training and Clinical Research between Stockholm County Council and Karolinska Institutet (ALF), Forte Foundation, Swedish Cancer Foundation, and Independent Research Fund Denmark.


Assuntos
Neoplasias Colorretais/epidemiologia , Doença de Crohn/epidemiologia , Vigilância da População , Adolescente , Adulto , Fatores Etários , Estudos de Casos e Controles , Colangite Esclerosante/epidemiologia , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Doença de Crohn/diagnóstico , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Suécia/epidemiologia , Adulto Jovem
19.
Lancet ; 395(10218): 123-131, 2020 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-31929014

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance paradigms, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account, such as by assessing CRC incidence by tumour stage, or stage-adjusted mortality from CRC. We aimed to compare both overall and country-specific risks of CRC mortality and incident CRC among patients with UC. METHODS: In this population-based cohort study of 96 447 patients with UC in Denmark (n=32 919) and Sweden (n=63 528), patients were followed up for CRC incidence and CRC mortality between Jan 1, 1969, and Dec 31, 2017, and compared with matched reference individuals from the general population (n=949 207). Patients with UC were selected from national registers and included in the analysis if they had two or more records with a relevant International Classification of Disease in the patient register (in the country in question) or one such record plus a colorectal biopsy report with a morphology code suggestive of inflammatory bowel disease. For every patient with UC, we selected matched reference individuals from the total population registers of Denmark and Sweden, who were matched for sex, age, birth year, and place of residence. We used Cox regression to compute hazard ratios (HRs) for incident CRC, and for CRC mortality, taking tumour stage into account. FINDINGS: During follow-up, we observed 1336 incident CRCs in the UC cohort (1·29 per 1000 person-years) and 9544 incident CRCs in reference individuals (0·82 per 1000 person-years; HR 1·66, 95% CI 1·57-1·76). In the UC cohort, 639 patients died from CRC (0·55 per 1000 person-years), compared with 4451 reference individuals (0·38 per 1000 person-years; HR 1·59, 95% CI 1·46-1·72) during the same time period. The CRC stage distribution in people with UC was less advanced (p<0·0001) than in matched reference individuals, but taking tumour stage into account, patients with UC and CRC remained at increased risk of CRC death (HR 1·54, 95% CI 1·33-1·78). The excess risks declined over calendar periods: during the last 5 years of follow-up (2013-17, Sweden only), the HR for incident CRC in people with UC was 1·38 (95% CI 1·20-1·60, or one additional case per 1058 patients with UC per 5 years) and the HR for death from CRC was 1·25 (95% CI 1·03-1·51, or one additional case per 3041 patients with UC per 5 years). INTERPRETATION: Compared with those without UC, individuals with UC are at increased risk of developing CRC, are diagnosed with less advanced CRC, and are at increased risk of dying from CRC, although these excess risks have declined substantially over time. There still seems to be room for improvement in international surveillance guidelines. FUNDING: The Swedish Medical Society, Karolinska Institutet, Stockholm County Council, Swedish Research Council, Swedish Foundation for Strategic Research, Independent Research Fund Denmark, Forte Foundation, Swedish Cancer Foundation.


Assuntos
Colite Ulcerativa/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Adulto , Idoso , Estudos de Coortes , Colite Ulcerativa/complicações , Colite Ulcerativa/mortalidade , Neoplasias Colorretais/mortalidade , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Sistema de Registros , Suécia/epidemiologia , Adulto Jovem
20.
Gastroenterology ; 158(6): 1574-1583.e2, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31926169

RESUMO

BACKGROUND & AIMS: Microscopic colitis shares pathogenetic mechanisms with inflammatory bowel disease (IBD). We studied the association between microscopic colitis and risk of incident IBD using data from a nationwide cohort study. METHODS: We conducted a prospective cohort study of all adults who received a diagnosis of microscopic colitis from 1990 through 2017 in Sweden and risk of incident IBD. Cases of microscopic colitis (n= 13,957) were identified through Systematized Nomenclature of Medicine codes from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, which included gastrointestinal pathology reports from all of Sweden's 28 centers. Individuals with microscopic colitis were matched to 5 general population controls (n = 66,820) and to unaffected siblings (n =13,943). Cox regression was used to estimate adjusted hazard ratio (aHRs) and 95% confidence intervals (CIs). RESULTS: Through December of 2017, we identified 323 incident cases of ulcerative colitis (UC) and 108 incident cases of Crohn's disease (CD) in patients with microscopic colitis compared with 94 UC and 42 CD cases in population comparators. Mean times from diagnosis of microscopic colitis to diagnosis of CD was 3.3 ± 3.2 years and to diagnosis of UC was 3.2 ± 3.5 years. In multivariable models, microscopic colitis was associated with an aHR of 12.6 (95% CI 8.8-18.1) for CD, 17.3 (95% CI 13.7-21.8) for UC, and 16.8 (95% CI 13.9-20.3) for IBD. The 10-year absolute excess risks of CD and UC were 0.9 (95% CI 0.7-1.1) and 2.6 (95% CI 2.2-2.9) percentage points, respectively. In sensitivity analyses, comparing patients with microscopic colitis with their unaffected siblings, the aHRs of CD and UC were 5.4 (95% CI 3.2-9.2) and 9.4 (95% CI 6.4-13.8), respectively. CONCLUSIONS: In a population-based study in Sweden, we found a significant increase in risk of incident IBD among patients with microscopic colitis. Future studies should focus on potential mechanisms underlying these observed associations.


Assuntos
Colite Microscópica/epidemiologia , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Adulto , Idoso , Biópsia/estatística & dados numéricos , Estudos de Casos e Controles , Colite Microscópica/complicações , Colite Microscópica/patologia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/etiologia , Colite Ulcerativa/patologia , Colo/patologia , Doença de Crohn/diagnóstico , Doença de Crohn/etiologia , Doença de Crohn/patologia , Feminino , Seguimentos , Humanos , Incidência , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Suécia/epidemiologia
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