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1.
BMJ Open ; 14(7): e083163, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39089718

RESUMO

INTRODUCTION: The absence of reliable prognostic markers poses a challenge to the management of inflammatory bowel disease (IBD). Patients with aggressive disease may not receive sufficient treatment with conventional 'step-up' therapy, whereas a top-down approach may expose patients with indolent disease to unnecessary treatment-related toxicity. The objective of the Nordic IBD treatment strategy trial (NORDTREAT) is to assess the feasibility of personalised therapy by stratifying patients according to a prognostic serum protein signature at diagnosis. METHODS AND ANALYSIS: NORDTREAT is a multicentre, biomarker-strategy design, open-label controlled trial. After screening consent, eligible patients are randomised (1:1) into one of two groups: a group with access to the protein signature and a group without access. In the access to protein signature group, patients displaying a protein signature suggestive of an increased risk of an aggressive disease course will be treated in line with a top-down treatment algorithm (anti-tumour necrosis factor agent with/without an immunomodulator). In contrast, those with a protein signature indicative of indolent disease will be excluded from the trial. Patients not in the access group receive treatment based on clinical management. This traditional management involves a stepwise escalation of treatment as determined by the investigator after failure of first-line treatment. After 52 weeks, outcomes are assessed in the subgroup of patients with a protein profile indicating a potentially severe disease trajectory. The primary endpoint is a composite of the proportion of patients with corticosteroid-free clinical and endoscopic remission at week 52. Surgical intervention due to IBD during follow-up will be defined as treatment failure. ETHICS AND DISSEMINATION: Ethical approval has been obtained, and recruitment is underway at sites in four participating Nordic countries (Denmark, Iceland, Norway and Sweden). Following trial completion and data analysis, the trial results will be submitted for publication in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT05180175; Pre-results. EudraCT number: 2019-002942-19.


Assuntos
Biomarcadores , Doenças Inflamatórias Intestinais , Humanos , Biomarcadores/sangue , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Prognóstico , Medicina de Precisão/métodos , Países Escandinavos e Nórdicos , Fatores Imunológicos/uso terapêutico
2.
Artigo em Inglês | MEDLINE | ID: mdl-38997818

RESUMO

BACKGROUND: Faecal biomarkers can be used to assess inflammatory bowel disease (IBD). AIM: To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD. METHODS: We included 65 patients with treatment-naïve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression. RESULTS: All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006). CONCLUSIONS: This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers.

3.
Am J Gastroenterol ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38994835

RESUMO

INTRODUCTION: We aimed to assess the risk of serious infection in patients with inflammatory bowel disease (IBD) treated with vedolizumab compared with those treated with anti-tumor necrosis factors (TNF) and the general population. METHODS: In this Swedish cohort study, treatment episodes were identified from nationwide health registers. We used Cox regression with propensity score-matched cohorts to estimate hazard ratios (HRs) for incident serious infections, defined as infections requiring hospital admission. RESULTS: During 1,376 treatment episodes in Crohn's disease, the rate of serious infections per 100 person-years (PY) was 5.18 (95% CI = 3.98-6.63) with vedolizumab vs 3.54 (95% CI = 2.50-4.85) with anti-TNF; HR = 1.72 (95% CI = 1.12-2.65), partly explained by more gastrointestinal infections. Compared with the rate of 0.75/100 PY (95% CI = 0.59-0.92) in a matched general population cohort, vedolizumab demonstrated higher risk (HR = 7.00; 95% CI = 5.04-9.72). During 1,294 treatment episodes in ulcerative colitis, the corresponding rates were 3.74/100 PY (95% CI = 2.66-5.11) with vedolizumab vs 3.42/100 PY (95% CI = 2.31-4.89) with anti-TNF; HR = 0.80 (95% CI = 0.47-1.36) during the initial 1.1 years and HR = 2.03 (95% CI = 0.65-6.32) after 1.1 years (truncated due to nonproportional hazards). Pneumonia accounted for 40% of all infections among anti-TNF, whereas no case was observed among vedolizumab episodes. Compared with the rate of 0.69/100 PYs (95% CI = 0.53-0.87) in a matched general population cohort, vedolizumab showed an HR of 5.45 (95% CI = 3.67-8.11). DISCUSSION: Vedolizumab was associated with increased risks of serious infections compared with anti-TNF in Crohn's disease but not in ulcerative colitis. Nonetheless, the panorama of serious infections seemed to differ between the drugs. Our findings underscore the importance of clinical awareness of infections and the safety profile of the 2 therapies.

4.
Nat Commun ; 15(1): 4567, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830848

RESUMO

Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.


Assuntos
Biomarcadores , Doenças Inflamatórias Intestinais , Lipidômica , Humanos , Criança , Lipidômica/métodos , Masculino , Feminino , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/metabolismo , Biomarcadores/sangue , Adolescente , Fezes/química , Fosfatidilcolinas/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Pré-Escolar , Complexo Antígeno L1 Leucocitário/sangue , Complexo Antígeno L1 Leucocitário/análise , Estudos de Coortes
5.
Eur Heart J ; 45(28): 2493-2504, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771865

RESUMO

BACKGROUND AND AIMS: Dysregulation of inflammatory and immune responses has been implicated in the pathogenesis of heart failure (HF). But even if inflammation is a prerequisite for inflammatory bowel disease (IBD), little is known about HF risk in IBD. METHODS: In this Swedish nationwide cohort, patients with biopsy-confirmed IBD were identified between 1969 and 2017 [n = 81 749, Crohn's disease (CD, n = 24 303), ulcerative colitis (UC, n = 45 709), and IBD-unclassified (IBD-U, n = 11 737)]. Each patient was matched with up to five general population reference individuals (n = 382 190) and IBD-free full siblings (n = 95 239) and followed until 31 December 2019. Flexible parametric survival models estimated the adjusted hazard ratio (aHR) and standardized cumulative incidence for HF, with 95% confidence intervals (CI). RESULTS: There were 5582 incident HF identified in IBD patients (incidence rate [IR]: 50.3/10 000 person-years) and 20 343 in reference individuals (IR: 37.9) during a median follow-up of 12.4 years. IBD patients had a higher risk of HF than reference individuals (aHR 1.19, 95% CI 1.15-1.23). This increased risk remained significant ≥20 years after IBD diagnosis, leading to one extra HF case per 130 IBD patients until then. The increased risk was also observed across IBD subtypes: CD (IR: 46.9 vs. 34.4; aHR 1.28 [1.20-1.36]), UC (IR: 50.1 vs. 39.7; aHR 1.14 [1.09-1.19]), and IBD-U (IR: 60.9 vs. 39.0; aHR 1.28 [1.16-1.42]). Sibling-controlled analyses showed slightly attenuated association (IBD: aHR 1.10 [1.03-1.19]). CONCLUSIONS: Patients with IBD had a moderately higher risk of developing HF for ≥20 years after IBD diagnosis than the general population.


Assuntos
Insuficiência Cardíaca , Doenças Inflamatórias Intestinais , Humanos , Suécia/epidemiologia , Masculino , Feminino , Insuficiência Cardíaca/epidemiologia , Adulto , Pessoa de Meia-Idade , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Incidência , Adulto Jovem , Idoso , Adolescente , Fatores de Risco , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/complicações , Doença de Crohn/epidemiologia , Doença de Crohn/complicações , Criança
6.
BMJ Open ; 14(5): e083144, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754881

RESUMO

INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death. METHODS AND ANALYSIS: We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits. ETHICS AND DISSEMINATION: This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. CLINICAL TRIAL REGISTRATION NUMBER: NCT05414578; Pre-results.


Assuntos
Biomarcadores , Doenças Inflamatórias Intestinais , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/terapia , Estudos Longitudinais , Estudos Multicêntricos como Assunto , Prognóstico , Estudos Prospectivos , Projetos de Pesquisa , Países Escandinavos e Nórdicos
7.
J Crohns Colitis ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518097

RESUMO

BACKGROUND AND AIMS: Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but the role of familial [genetic and environmental] factors in this shared susceptibility is largely unknown. We compared the risk of SpA in first-degree relatives [FDRs] and spouses of IBD patients with FDRs and spouses of matched population-based reference individuals. METHODS: We identified 147,080 FDRs and 25,945 spouses of patients with incident IBD [N=39,203] during 2006-2016 and 1,453,429 FDRs and 258,098 spouses of matched reference individuals [N=390,490], by linking nationwide Swedish registers and gastrointestinal biopsy data. Study participants were followed 1987-2017. Cox regression was used to estimate hazard ratios [HRs] of SpA. RESULTS: During follow-up, 2,430 FDRs of IBD patients [6.5/10,000 person-years] and 17,761 FDRs of reference individuals [4.8/10,000 person-years] were diagnosed with SpA, corresponding to an HR of 1.35 [95%CI:1.29,1.41]. In subgroup analyses, the increased risk of SpA was most pronounced in FDRs of Crohn's disease patients [HR=1.44; 95%CI:1.34,1.56] and of IBD patients aged <18 years at diagnosis [HR=1.46; 95%CI: 1.27,1.68]. IBD patient's spouses also had a higher SpA rate than reference individuals' spouses, but the difference was less pronounced [4.3 vs. 3.5/10,000 person-years; HR=1.22; 95%CI:1.09,1.37]. No subgroup-specific risk pattern was identified among spouses. CONCLUSIONS: The observed shared familial risks between IBD and SpA support shared genetic factors in their pathogenesis. However, spouses of IBD patients were also at increased risk for SpA, reflecting the influence of environmental exposures or similarities in health-seeking patterns.

8.
Am J Gastroenterol ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38315442

RESUMO

OBJECTIVES: Despite a suggested link between inflammatory bowel disease (IBD) and myocarditis, the association has not been well-established. This study aimed to investigate the long-term risk of myocarditis in patients with IBD. METHODS: This nationwide cohort involved all patients with biopsy-confirmed IBD in Sweden (1969-2017) (n=83,264, Crohn's disease [CD, n=24,738], ulcerative colitis [UC, n=46,409], and IBD-unclassified [IBD-U, n=12,117]), general population reference individuals (n=391,344), and IBD-free full siblings (n=96,149), and followed until 2019. Primary outcome was incident myocarditis and secondary outcome was severe myocarditis (complicated with heart failure, death, or readmission). Flexible parametric survival models were used to estimate adjusted hazard ratios (aHR) and cumulative incidence of outcomes, along with 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12 years, there were 256 myocarditis cases in IBD patients (incidence rate [IR]=22.6/100,000 person-years) and 710 in reference individuals (IR=12.9), with an aHR of 1.55 (95%CI: 1.33 to 1.81). The increased risk persisted through 20 years after IBD diagnosis, corresponding to one extra myocarditis case in 735 IBD patients until then. This increased risk was observed in CD (aHR=1.48 [1.11 to 1.97]) and UC (aHR=1.58 [1.30 to 1.93]). IBD was also associated with severe myocarditis (IR: 10.1 vs. 3.5; aHR=2.44 [1.89 to 3.15]), irrespective of IBD subtypes (CD: aHR=2.39 [1.43 to 4.01], UC: aHR=2.82 [1.99 to 4.00], and IBD-U: aHR=3.14 [1.55 to 6.33]). Sibling comparison analyses yielded similar results. CONCLUSIONS: Patients with IBD had an increased risk of myocarditis, especially severe myocarditis, for ≥20 years after diagnosis, but absolute risks were low.

9.
Gastroenterology ; 166(5): 802-814.e18, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38331202

RESUMO

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is linked to reduced female fertility, but it is unclear how fertility rates vary by histologic disease activity. METHODS: Nationwide IBD cohort of Swedish women aged 15 to 44 years. We examined fertility rates during periods with vs without histologic inflammation (n = 21,046; follow-up, 1990-2016) and during periods with vs without clinical activity (IBD-related hospitalization, surgery, or treatment escalation) (n = 24,995; follow-up, 2006-2020). Accounting for sociodemographics and comorbidities, we used Poisson regression to estimate adjusted fertility rate ratios (aFRRs) for live births conceived during 12-month periods of histologic inflammation (vs histologic remission) and 3-month periods of clinically active IBD (vs quiescent IBD). RESULTS: During periods with vs without histologic inflammation, there were 6.35 (95% confidence interval [CI], 5.98-6.73) and 7.09 (95% CI, 6.48-7.70) live births conceived per 100 person-years of follow-up, respectively, or 1 fewer child per 14 women with 10 years of histologic inflammation (aFRR, 0.90; 95% CI, 0.81-1.00). In women with histologic inflammation, fertility was similarly reduced in ulcerative colitis (UC) (aFRR, 0.89 [95% CI, 0.78-1.02]) and Crohn's disease (CD) (aFRR, 0.86 [95% CI, 0.72-1.04]). Clinical IBD activity was associated with an aFRR of 0.76 (95% CI, 0.72-0.79) or 1 fewer child per 6 women with 10 years of clinical activity. Fertility was reduced in clinically active UC (aFRR, 0.75 [95% CI, 0.70-0.81]) and CD (aFRR, 0.76 [95% CI, 0.70-0.82]). Finally, among women with clinically quiescent IBD, histologic inflammation (vs histologic remission) was associated with reduced fertility (aFRR, 0.85 [95% CI, 0.73-0.98]). CONCLUSIONS: An association between histologic and clinical activity and reduced female fertility in CD and UC was found. Notably, histologic inflammation was also linked to reduced fertility in women with clinically quiescent IBD.


Assuntos
Colite Ulcerativa , Infertilidade Feminina , Nascido Vivo , Humanos , Feminino , Adulto , Suécia/epidemiologia , Adulto Jovem , Adolescente , Gravidez , Colite Ulcerativa/patologia , Colite Ulcerativa/terapia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/diagnóstico , Infertilidade Feminina/etiologia , Infertilidade Feminina/epidemiologia , Nascido Vivo/epidemiologia , Doença de Crohn/patologia , Doença de Crohn/epidemiologia , Doença de Crohn/terapia , Doença de Crohn/diagnóstico , Fertilidade , Sistema de Registros
10.
Diagnostics (Basel) ; 14(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38396390

RESUMO

Abnormal visceral perception and motor function are often observed in patients with fecal incontinence, evacuation disorders and irritable bowel syndrome. The international anorectal physiology working group has proposed a standardization for anorectal function assessment, where rectal sensitivity testing is performed using an elastic balloon attached to a high-resolution anorectal manometry (HRAM) catheter. Rectal compliance, another component of rectal function evaluation, is a pressure-volume relationship that refers to the rectum's ability to stretch and expand as it receives and holds fecal matter. There are no data available regarding the possibility of compliance testing using HRAM, although this is theoretically possible by correcting for the elastic balloon's intrinsic properties. The gold standard for measurement of visceral sensitivity and compliance is the rectal barostat, according to the procedure described by the European COST action GENIEUR group. Data on the agreement between the two different procedures are scarce. Hence, we performed a comparative study of the HRAM and barostat investigations in 26 healthy individuals. We hypothesized that by inflating the balloon before the examination, rectal compliance can be measured with HRAM investigations, and we examined correlations and levels of agreement between the methods. Our results demonstrate that assessing rectal compliance with HRAM is technically possible; however, a strong correlation with the rectal barostat was only observed at the maximum tolerable volume (Spearman's rho = 0.7, p = 0.02). We only found moderate correlations (Spearman's rho = 0.562, p = 0.019) for compliance according to the barostat methodology and for rectal sensibility testing (Spearman's rho = 0.57, p = 0.03 for maximum tolerable volume). Bland-Altman plots showed poor levels of agreement between the methods. We conclude that HRAM and the rectal barostat cannot be used interchangeably for compliance or sensitivity assessments. We suggest the development of a non-elastic balloon with a fixed size and shape to assess rectal sensory function and compliance in HRAM testing.

12.
Clin Gastroenterol Hepatol ; 22(4): 831-846, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37913937

RESUMO

BACKGROUND & AIMS: Individuals with inflammatory bowel disease (IBD) are at increased risk of serious infections, but whether this risk varies by histologic disease activity is unclear. METHODS: This was a national population-based study of 55,626 individuals diagnosed with IBD in 1990 to 2016 with longitudinal data on ileocolorectal biopsy specimens followed up through 2016. Serious infections were defined as having an inpatient infectious disease diagnosis in the Swedish National Patient Register. We used Cox regression to estimate hazard ratios (HRs) for serious infections in the 12 months after documentation of histologic inflammation (vs histologic remission), adjusting for social and demographic factors, chronic comorbidities, prior IBD-related surgery, and hospitalization. We also adjusted for IBD-related medications in sensitivity analyses. RESULTS: With histologic inflammation vs remission, there was 4.62 (95% CI, 4.46-4.78) and 2.53 (95% CI, 2.36-2.70) serious infections per 100 person-years of follow-up, respectively (adjusted HR [aHR], 1.59; 95% CI, 1.48-1.72). Histologic inflammation (vs remission) was associated with an increased risk of serious infections in ulcerative colitis (aHR, 1.68; 95% CI, 1.51-1.87) and Crohn's disease (aHR, 1.59; 95% CI, 1.40-1.80). The aHRs of sepsis and opportunistic infections were 1.66 (95% CI, 1.28-2.15) and 1.71 (95% CI, 1.22-2.41), respectively. Overall, results were consistent across age groups, sex, and education level, and remained largely unchanged after adjustment for IBD-related medications (aHR, 1.47; 95% CI, 1.34-1.61). CONCLUSIONS: Histologic inflammation of IBD was an independent risk factor of serious infections, including sepsis, suggesting that achieving histologic remission may reduce infections in IBD. The study was approved by the Stockholm Ethics Review Board (approval numbers 2014/1287-31/4, 2018/972-32, and 2021-06209-01).


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Sepse , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doença de Crohn/complicações , Colite Ulcerativa/complicações , Fatores de Risco , Inflamação , Sepse/complicações
13.
Am J Gastroenterol ; 119(2): 313-322, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37721310

RESUMO

INTRODUCTION: Data suggest atherosclerotic-related inflammation may play a role in the pathogenesis of inflammatory bowel disease (IBD), but large-scale studies are missing. METHODS: In this nationwide case-control study, we used the Swedish Patient Register and the Epidemiology Strengthened by histoPathology Reports in Sweden cohort to identify adult cases of incident IBD between 2002 and 2021, with each case matched to up to 10 general population controls. We used conditional logistic regression to calculate odds ratios (OR) for exposure to an atherosclerotic-related condition (myocardial infarction, thromboembolic stroke, or atherosclerosis itself) before being diagnosed with IBD. RESULTS: There were a total of 56,212 individuals with IBD and 531,014 controls. Of them, 2,334 (4.2%) cases and 18,222 (3.4%) controls had a prior diagnosis of an atherosclerotic-related condition, corresponding to an OR of 1.30 (95% confidence interval [CI] 1.24-1.37). Results were statistically significant for both Crohn's disease (OR 1.37, 95% CI 1.26-1.48) and ulcerative colitis (OR 1.27, 95% CI 1.20-1.35) and for individuals who developed IBD at 40-59 years of age and 60 years or older. In addition, associations persisted when adjusting for underlying comorbidities, including the presence of immune-mediated diseases and prior aspirin and/or statin use. The highest odds of an atherosclerotic-related condition were seen in the 6-12 months before IBD diagnosis, though odds were increased even ≥5 years before. A higher magnitude of odds was also observed when having 2 or more atherosclerotic-related conditions when compared with having only 1 condition. DISCUSSION: A history of an atherosclerotic-related condition is associated with increased odds of developing IBD, particularly among older adults. Future studies should investigate whether drugs targeting atherosclerotic-related inflammation may prevent IBD in higher-risk individuals.


Assuntos
Aterosclerose , Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Idoso , Estudos de Casos e Controles , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Colite Ulcerativa/epidemiologia , Fatores de Risco , Inflamação/complicações , Aterosclerose/epidemiologia
14.
J Crohns Colitis ; 18(3): 349-359, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37768647

RESUMO

BACKGROUND AND AIMS: Microscopic colitis [MC] is currently regarded as an inflammatory bowel disease that manifests as two subtypes: collagenous colitis [CC] and lymphocytic colitis [LC]. Whether these represent a clinical continuum or distinct entities is, however, an open question. Genetic investigations may contribute important insight into their respective pathophysiologies. METHODS: We conducted a genome-wide association study [GWAS] meta-analysis in 1498 CC, 373 LC patients, and 13 487 controls from Europe and the USA, combined with publicly available MC GWAS data from UK Biobank and FinnGen [2599 MC cases and 552 343 controls in total]. Human leukocyte antigen [HLA] alleles and polymorphic residues were imputed and tested for association, including conditional analyses for the identification of key causative variants and residues. Genetic correlations with other traits and diagnoses were also studied. RESULTS: We detected strong HLA association with CC, and conditional analyses highlighted the DRB1*03:01 allele and its residues Y26, N77, and R74 as key to this association (best p = 1.4 × 10-23, odds ratio [OR] = 1.96). Nominally significant genetic correlations were detected between CC and pneumonia [rg = 0.77; p = 0.048] and oesophageal diseases [rg = 0.45, p = 0.023]. An additional locus was identified in MC GWAS analyses near the CLEC16A and RMI2 genes on chromosome 16 [rs35099084, p = 2.0 × 10-8, OR = 1.31]. No significant association was detected for LC. CONCLUSION: Our results suggest CC and LC have distinct pathophysiological underpinnings, characterised by an HLA predisposing role only in CC. This challenges existing classifications, eventually calling for a re-evaluation of the utility of MC umbrella definitions.


Assuntos
Colite Colagenosa , Colite Linfocítica , Colite Microscópica , Humanos , Estudo de Associação Genômica Ampla , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe II , Colite Microscópica/genética , Colite Linfocítica/genética
15.
Scand J Gastroenterol ; 59(2): 150-155, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37882356

RESUMO

BACKGROUND: Proactive therapeutic drug monitoring (TDM) is often challenged by long turnaround time when using enzyme-linked immunosorbent assays (ELISAs), especially when analyses are centralised. Point-of-care tests (POCTs) allow rapid assessments, but data on their agreement with existing in-house methodologies are scarce. OBJECTIVE: To examine the agreement between a POCT by ProciseDx (San Diego, CA) and the most frequently used in-house ELISA for infliximab (IFX) quantification in Sweden. METHODS: Serum samples were analysed using the in-house ELISA, Karolinska University Hospital, Stockholm, Sweden and a POCT by ProciseDx (San Diego, CA). Agreement was assessed and differences were examined. RESULTS: Samples from 61 inflammatory bowel disease (IBD) patients were analysed with a median IFX concentration of 7.9 µg/mL (interquartile range (IQR) 5.5-13) for the POCT and 7.9 µg/mL (IQR 5.2-12) for the ELISA (Pearson's correlation coefficient = 0.95 (95% CI 0.92-0.97, p < .01)). A Passing-Bablok regression yielded an intercept of -0.44 and a slope of 1.09. The Bland-Altman plot showed a systemic bias of -0.77 µg/mL (95% CI -0.18 to -1.4) between the methods. The upper limit of agreement was 3.7 (95% CI 2.7-4.8) (µg/mL), whereas the lower limit agreement was -5.3 (95% CI -6.3 to -4.3) (µg/mL). An excellent reliability was observed, intraclass correlation showed = 0.94 (95% CI 0.89-0.96, p < .0001). When defining IFX concentration as subtherapeutic (<3.0 µg/mL), therapeutic (3.0-7.0 µg/mL) or supratherapeutic (>7.0 µg/mL) drug levels, Kappa statistics showed a substantial agreement (0.79). CONCLUSIONS: The POCT by ProciseDx (San Diego, CA) demonstrated a good agreement with the in-house ELISA, supporting its use for rapid IFX quantification.


Assuntos
Doenças Inflamatórias Intestinais , Humanos , Infliximab/uso terapêutico , Reprodutibilidade dos Testes , Ensaio de Imunoadsorção Enzimática/métodos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Testes Imediatos , Monitoramento de Medicamentos/métodos , Fármacos Gastrointestinais/uso terapêutico
16.
J Crohns Colitis ; 18(1): 91-105, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-37586038

RESUMO

BACKGROUND AND AIMS: Treatment of ulcerative colitis [UC] requires a patient-centric definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative, we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process. METHODS: The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before Round 3. Consensus was met if ≥67% of the panel agreed. Statements without consensus in Rounds 1 and 2 were revised or discarded after Round 3. RESULTS: The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials [rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use] with additional patient-reported symptoms [bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance]. The panel agreed on scoring systems and thresholds for many aspects. CONCLUSIONS: Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multicomponent tool and will adopt comprehensive disease control as a treatment target in clinical practice and trials.


Assuntos
Colite Ulcerativa , Humanos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Consenso , Técnica Delphi , Qualidade de Vida , Endoscopia Gastrointestinal
17.
United European Gastroenterol J ; 12(1): 34-43, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38058270

RESUMO

BACKGROUND: Earlier studies on the possible association between eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) have been contradictory. METHODS: Patients with biopsy-verified EoE diagnosed between 1990 and 2017 in Sweden (n = 1587) were age- and sex-matched with up to five general population reference individuals (n = 7808). EoE was defined using pathology reports from all 28 pathology centers in Sweden (the ESPRESSO study). Multivariate Cox regression then estimated hazard ratios for future IBD. IBD was defined based on the international classification of disease codes and histopathology codes. In secondary analyses, sibling comparators were used to further reduce potential familial confounding. Additionally, we performed logistic regression examining earlier IBD in EoE. RESULTS: During follow-up until 2020, 16 (0.01%) EoE patients and 21 (0.003%) general population reference individuals diagnosed with IBD, corresponding to a 3.5-fold increased risk of future IBD (aHR = 3.56; 95% CI 1.79-7.11). EoE was linked to Crohn's disease (aHR = 3.39 [95% CI 1.02-9.60]) but not to ulcerative colitis (aHR = 1.37; 95% CI 0.38-4.86). Compared to their siblings, patients with EoE were at a 2.48-fold increased risk of IBD (aHR = 2.48; 95% CI 0.92-6.70). Earlier IBD was 15 times more likely in EoE patients than in matched reference individuals (odds ratio, 15.39; 95% CI 7.68-33.59). CONCLUSION: In this nationwide cohort study, EoE was associated with a 3.5-fold increased risk of later IBD diagnosis. This risk increase may be due to shared genetic or early environmental risk factors, but also surveillance bias could play a role.


Assuntos
Doença de Crohn , Esofagite Eosinofílica , Doenças Inflamatórias Intestinais , Humanos , Suécia/epidemiologia , Estudos de Coortes , Esofagite Eosinofílica/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia
18.
J Clin Med ; 12(19)2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37834994

RESUMO

As the patents for biologic originator drugs expire, biosimilars are emerging as cost-effective alternatives within healthcare systems. Addressing various challenges in the clinical management of inflammatory bowel disease (IBD) remains crucial. To shed light on physicians' current knowledge, beliefs, practical approaches, and concerns related to biosimilar adoption-whether initiating a biosimilar, transitioning from an originator to a biosimilar, or switching between biosimilars (including multiple switches and reverse switching)-a global survey was conducted. Fifteen physicians with expertise in the field of IBD from 13 countries attended a virtual international consensus meeting to develop practical guidance regarding biosimilar adoption worldwide, considering the survey results. This consensus centered on 10 key statements covering biosimilar effectiveness, safety, indications, rationale, multiple switches, therapeutic drug monitoring of biosimilars, non-medical switching, and future perspectives. Ultimately, the consensus affirmed that biosimilars are equally effective and safe when compared to originator drugs. They are considered suitable for both biologic-naïve patients and those who have previously been treated with originator drugs, with cost reduction being the primary motivation for transitioning from an originator drug to a biosimilar.

19.
PLoS Med ; 20(10): e1004305, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37856566

RESUMO

BACKGROUND: Although previous evidence has suggested an increased risk of cardiovascular disease (CVD) in patients with inflammatory bowel disease (IBD), its association with arrhythmias is inconclusive. In this study, we aimed to explore the long-term risk of arrhythmias in patients with IBD. METHODS AND FINDINGS: Through a nationwide histopathology cohort, we identified patients with biopsy-confirmed IBD in Sweden during 1969 to 2017, including Crohn's disease (CD: n = 24,954; median age at diagnosis: 38.4 years; female: 52.2%), ulcerative colitis (UC: n = 46,856; 42.1 years; 46.3%), and IBD-unclassified (IBD-U: n = 12,067; 43.8 years; 49.6%), as well as their matched reference individuals and IBD-free full siblings. Outcomes included overall and specific arrhythmias (e.g., atrial fibrillation/flutter, bradyarrhythmias, other supraventricular arrhythmias, and ventricular arrhythmias/cardiac arrest). Flexible parametric survival models estimated hazard ratios (aHR) with 95% confidence intervals (95% CIs), after adjustment for birth year, sex, county of residence, calendar year, country of birth, educational attainment, number of healthcare visits, and cardiovascular-related comorbidities. Over a median of approximately 10 years of follow-up, 1,904 (7.6%) patients with CD, 4,154 (8.9%) patients with UC, and 990 (8.2%) patients with IBD-U developed arrhythmias, compared with 6.7%, 7.5%, and 6.0% in reference individuals, respectively. Compared with reference individuals, overall arrhythmias were increased in patients with CD [54.6 versus 46.1 per 10,000 person-years; aHR = 1.15 (95% CI [1.09, 1.21], P < 0.001)], patients with UC [64.7 versus 53.3 per 10,000 person-years; aHR = 1.14 (95% CI [1.10, 1.18], P < 0.001)], and patients with IBD-U [78.1 versus 53.5 per 10,000 person-years; aHR = 1.30 (95% CI [1.20, 1.41], P < 0.001)]. The increased risk persisted 25 years after diagnosis, corresponding to 1 extra arrhythmia case per 80 CD, 58 UC, and 29 IBD-U cases over the same period. Patients with IBD also had a significantly increased risk of specific arrhythmias, except for bradyarrhythmias. Sibling comparison analyses confirmed the main findings. Study limitations include lack of clinical data to define IBD activity, not considering the potential role of IBD medications and disease activity, and the potential residual confounding from unmeasured factors for arrhythmias. CONCLUSIONS: In this study, we observed that patients with IBD were at an increased risk of developing arrhythmias. The excess risk persisted even 25 years after IBD diagnosis. Our findings indicate a need for awareness of this excess risk among healthcare professionals.


Assuntos
Fibrilação Atrial , Doenças Inflamatórias Intestinais , Humanos , Feminino , Adulto , Irmãos , Estudos de Coortes , Bradicardia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico
20.
EClinicalMedicine ; 63: 102182, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37662517

RESUMO

Background: Statin use has been linked to a reduced risk of advanced colorectal adenomas, but its association with colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) - a high risk population for CRC - remains inconclusive. Methods: From a nationwide IBD cohort in Sweden, we identified 5273 statin users and 5273 non-statin users (1:1 propensity score matching) from July 2006 to December 2018. Statin use was defined as the first filled prescription for ≥30 cumulative defined daily doses and followed until December 2019. Primary outcome was incident CRC. Secondary outcomes were CRC-related mortality and all-cause mortality. Cox regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Findings: During a median follow-up of 5.6 years, 70 statin users (incidence rate (IR): 21.2 per 10,000 person-years) versus 90 non-statin users (IR: 29.2) were diagnosed with incident CRC (rate difference (RD), -8.0 (95% CIs: -15.8 to -0.2 per 10,000 person-years); aHR = 0.76 (95% CIs: 0.61 to 0.96)). The benefit for incident CRC was duration-dependent in a nested case-control design: as compared to short-term use (30 days to <1 year), the adjusted odd ratios were 0.59 (0.25 to 1.43) for 1 to <2 years of use, 0.46 (0.21 to 0.98) for 2 to <5 years of use, and 0.38 (0.16 to 0.86) for ≥5 years of use (Pfor tread = 0.016). Compared with non-statin users, statin users also had a decreased risk for CRC-related mortality (IR: 6.0 vs. 11.9; RD, -5.9 (-10.5 to -1.2); aHR, 0.56 (0.37 to 0.83)) and all-cause mortality (IR: 156.4 vs. 231.4; RD, -75.0 (-96.6 to -53.4); aHR, 0.63 (0.57 to 0.69)). Interpretation: Statin use was associated with a lower risk of incident CRC, CRC-related mortality, and all-cause mortality. The benefit for incident CRC was duration-dependent, with a significantly lower risk after ≥2 years of statin use. Funding: This research was supported by Forte (i.e., the Swedish Research Council for Health, Working Life and Welfare).

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