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1. Cumulative exposure to immunomodulators increases risk of cervical neoplasia in women with inflammatory bowel disease.

Author

Kreijne, J.E., Goetgebuer, R.L., Erler, N.S., Boer, N.K. de, Siebers, A.G., Dijkstra, G., Kemenade, F.A. van, Hoentjen, F., Oldenburg, B., Meulen, A.E. van der, Ponsioen, C.I.J., Pierik, M.J., Woude, C.J. van der, Vries, A.C. de, Kreijne, J.E., Goetgebuer, R.L., Erler, N.S., Boer, N.K. de, Siebers, A.G., Dijkstra, G., Kemenade, F.A. van, Hoentjen, F., Oldenburg, B., Meulen, A.E. van der, Ponsioen, C.I.J., Pierik, M.J., Woude, C.J. van der, and Vries, A.C. de

Abstract

01 juli 2023, Item does not contain fulltext, BACKGROUND: Women with inflammatory bowel disease (IBD) are at increased risk of high-grade cervical intraepithelial neoplasia and cervical cancer (CIN2+). AIM: To assess the association between cumulative exposure to immunomodulators (IM) and biologic agents (BIO) for IBD and CIN2+ METHODS: Adult women diagnosed with IBD before December 31st 2016 in the Dutch IBD biobank with available cervical records in the nationwide cytopathology database were identified. CIN2+ incidence rates in IM- (i.e., thiopurines, methotrexate, tacrolimus and cyclosporine) and BIO- (anti-tumour necrosis factor, vedolizumab and ustekinumab) exposed patients were compared to unexposed patients and risk factors were assessed. Cumulative exposure to immunosuppressive drugs was evaluated in extended time-dependent Cox-regression models. RESULTS: The study cohort comprised 1981 women with IBD: 99 (5%) developed CIN2+ during median follow-up of 17.2 years [IQR 14.6]. In total, 1305 (66%) women were exposed to immunosuppressive drugs (IM 58%, BIO 40%, IM and BIO 33%). CIN2+ risk increased per year of exposure to IM (HR 1.16, 95% CI 1.08-1.25). No association was observed between cumulative exposure to BIO or both BIO and IM and CIN2+. In multivariate analysis, smoking (HR 2.73, 95%CI 1.77-4.37) and 5-yearly screening frequency (HR 1.74, 95% CI 1.33-2.27) were also risk factors for CIN2+ detection. CONCLUSION: Cumulative exposure to IM is associated with increased risk of CIN2+ in women with IBD. In addition to active counselling of women with IBD to participate in cervical screening programs, further assessment of the benefit of intensified screening of women with IBD on long-term IM exposure is warranted.

Published
2023

2. Reply

Author

Straatmijer, T., Meulen, A.E. van der, Duijvestein, M., Straatmijer, T., Meulen, A.E. van der, and Duijvestein, M.

Abstract

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Published
2023

3. Impact of timing of primary ileocecal resection on prognosis in patients with Crohn's disease.

Author

Beelen, E.M.J., Arkenbosch, J.H.C., Erler, N.S., Sleutjes, J.A.M., Hoentjen, F., Bodelier, A.G.L., Dijkstra, G., Romberg-Camps, M., Boer, N.K. de, Stassen, L.P., Meulen, A.E. van der, West, R., Ruler, O. van, Woude, C.J. van der, Vries, A.C.H. de, Beelen, E.M.J., Arkenbosch, J.H.C., Erler, N.S., Sleutjes, J.A.M., Hoentjen, F., Bodelier, A.G.L., Dijkstra, G., Romberg-Camps, M., Boer, N.K. de, Stassen, L.P., Meulen, A.E. van der, West, R., Ruler, O. van, Woude, C.J. van der, and Vries, A.C.H. de

Abstract

Contains fulltext : 296934.pdf (Publisher’s version ) (Open Access), BACKGROUND: The advantage of early ileocecal resection after Crohn's disease diagnosis is a matter of debate. This study aims to assess the timing of ileocecal resection on prognosis, after correction for possible confounders. METHODS: Patients with Crohn's disease with primary ileocecal resection between 2000 and 2019 were included in a retrospective multicentre cohort. The primary endpoint was endoscopic recurrence (Rutgeerts score ≥i2b) within 18 months. Secondary endpoints were escalation of inflammatory bowel disease medication within 18 months and re-resection during follow-up. The association between timing of ileocecal resection and these endpoints was investigated using multivariable proportional hazard models, corrected for covariates including Montreal classification, postoperative prophylaxis, smoking, indication for surgery, medication before ileocecal resection, perianal fistulas, surgical approach, histology, length of resected segment and calendar year. RESULTS: In 822 patients ileocecal resection was performed after a median of 3.1 years (i.q.r. 0.7-8.0) after Crohn's disease diagnosis. The lowest incidence of endoscopic recurrence, escalation of inflammatory bowel disease medication and re-resection was observed for patients undergoing ileocecal resection shortly after diagnosis (0-1 months). After correction for covariates, patients with ileocecal resection at 0, 4 and 12 months after diagnosis had a cumulative incidence of 35 per cent, 48 per cent and 39 per cent for endoscopic recurrence, 20 per cent, 29 per cent and 28 per cent for escalation of inflammatory bowel disease medication and 20 per cent, 30 per cent and 34 per cent for re-resection, respectively. In the multivariable model ileocolonic disease (HR 1.39 (95 per cent c.i. 1.05 to 1.86)), microscopic inflammation of proximal and distal resection margins (HR 2.20 (95 per cent c.i. 1.21 to 3.87)) and postoperative prophylactic biological and immunomodulator (HR 0.16 (95 per cent c.i. 0.05

Published
2023

4. Retreatment with anti-tumor necrosis factor therapy in combination with an immunomodulator for recurrence of Crohn's disease after ileocecal resection results in prolonged continuation as compared to anti-tumor necrosis factor monotherapy

Author

Huinink, S.T., Beelen, E.M.J., Huinink, T.T., Hoentjen, F., Bodelier, A.G.L., Dijkstra, G., Romberg-Camps, M., Boer, N.K. de, Stassen, L.P.S., Meulen, A.E. van der, West, R., Ruler, O. van, Woude, C.J. van der, Vries, A.C. de, and Dutch ICC

Subjects
Crohn's disease, tumor necrosis factor inhibitors, ileocecal resection, retreatment
Abstract

Background: A considerable proportion of Crohn's disease patients that undergo ileocecal resection (ICR) have failed anti-tumor necrosis factor (TNF) therapy preoperatively. This study aimed to assess the effectiveness of retreatment of anti-TNF therapy in patients with postoperative recurrence. Methods: A real-world cohort study was performed on Crohn's disease patients who underwent primary ICR after anti-TNF therapy failure, and who were retreated with anti-TNF therapy for postoperative symptomatic Crohn's disease. The primary outcome was treatment failure (the need for (re)introduction of corticosteroids, immunosuppressants, or biologicals or the need for re-resection). Sub-analyses were performed on the nature of preoperative anti-TNF failure (primary non-response, secondary loss of response, intolerance), indication for ICR (refractory, stricturing, penetrating disease), combination therapy with immunomodulators, retreatment with the same anti-TNF agent and preoperative exposure to 1 vs. >1 anti-TNF agents. Results: In total, 66 of 364 patients retreated with anti-TNF therapy following ICR. Cumulative rates of treatment failure at 1 and 2 years were 28% and 47%. Treatment failure rate at 2 years was significantly lower in patients receiving combination therapy as compared to anti-TNF monotherapy (30% vs. 49%, P = 0.02). No difference in treatment failure was found with regards to the nature of preoperative anti-TNF failure (P = 0.76), indication for ICR (P = 0.88) switch of anti-TNF agent (P = 0.55) agent, and preoperative exposure to 1 vs. >1 anti-TNF agents (P = 0.88). Conclusion: Retreatment with anti-TNF therapy for postoperative Crohn's disease recurrence is a valid strategy after preoperative failure. Combination therapy is associated with a lower rate of treatment failure.

Published
2023

5. Genetic Risk Scores Identify Genetic Aetiology of Inflammatory Bowel Disease Phenotypes

Author

Voskuil, M.D., Spekhorst, L.M., Sloot, K.W.J. van der, Jansen, B.H., Dijkstra, G., Woude, C.J. van der, Hoentjen, F., Pierik, M.J., Meulen, A.E. van der, Boer, N.K.H. de, Lowenberg, M., Oldenburg, B., Festen, E.A.M., Weersma, R.K., Parelsnoer Inst, Dutch Initiative Crohn Colitis, Translational Immunology Groningen (TRIGR), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), RS: NUTRIM - R2 - Liver and digestive health, Gastroenterology and hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, and Gastroenterology & Hepatology

Subjects
Male, 0301 basic medicine, Oncology, LOCI, Genome-wide association study, Disease, SUSCEPTIBILITY, Inflammatory bowel disease, 0302 clinical medicine, Crohn Disease, Risk Factors, Pleiotropy, Medicine, Digestive System Surgical Procedures, Netherlands, Gastroenterology, phenotypes, General Medicine, Middle Aged, PRIMARY SCLEROSING CHOLANGITIS, Ulcerative colitis, CROHNS-DISEASE, 030220 oncology & carcinogenesis, Cohort, Female, Symptom Assessment, SMOKING, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Adult, medicine.medical_specialty, Cholangitis, Sclerosing, Primary sclerosing cholangitis, 03 medical and health sciences, inflammatory bowel disease, Internal medicine, Genetic variation, Genetics, Humans, Genetic Testing, GENOME-WIDE ASSOCIATION, Genetic Association Studies, business.industry, medicine.disease, digestive system diseases, Patient Care Management, 030104 developmental biology, Pharmacogenetics, DENSITY, Colitis, Ulcerative, business, Genome-Wide Association Study
Abstract

Background and Aims Inflammatory bowel disease [IBD] phenotypes are very heterogeneous between patients, and current clinical and molecular classifications do not accurately predict the course that IBD will take over time. Genetic determinants of disease phenotypes remain largely unknown but could aid drug development and allow for personalised management. We used genetic risk scores [GRS] to disentangle the genetic contributions to IBD phenotypes. Methods Clinical characteristics and imputed genome-wide genetic array data of patients with IBD were obtained from two independent cohorts [cohort A, n = 1097; cohort B, n = 2156]. Genetic risk scoring [GRS] was used to assess genetic aetiology shared across traits and IBD phenotypes. Significant GRS–phenotype (false-discovery rate [FDR] corrected p Results Crohn’s disease [CD] GRS were associated with fibrostenotic CD [R2 = 7.4%, FDR = 0.02] and ileocaecal resection [R2 = 4.1%, FDR = 1.6E-03], and this remained significant after correcting for previously identified clinical and genetic risk factors. Ulcerative colitis [UC] GRS [R2 = 7.1%, FDR = 0.02] and primary sclerosing cholangitis [PSC] GRS [R2 = 3.6%, FDR = 0.03] were associated with colonic CD, and these two associations were largely driven by genetic variation in MHC. We also observed pleiotropy between PSC genetic risk and smoking behaviour [R2 = 1.7%, FDR = 0.04]. Conclusions Patients with a higher genetic burden of CD are more likely to develop fibrostenotic disease and undergo ileocaecal resection, whereas colonic CD shares genetic aetiology with PSC and UC that is largely driven by variation in MHC. These results further our understanding of specific IBD phenotypes.

Published
2021
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6. Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility

Author

Sazonovs, A., Stevens, C.R., Venkataraman, G.R., Yuan, K., Avila, B., Abreu, M.T., Ahmad, T., Allez, M., Ananthakrishnan, A.N., Atzmon, G., Baras, A., Barrett, J.C., Barzilai, N., Beaugerie, L., Beecham, A., Bernstein, C.N., Bitton, A., Bokemeyer, B., Chan, A., Chung, D., Cleynen, I., Cosnes, J., Cutler, D.J., Daly, A., Damas, O.M., Datta, L.W., Dawany, N., Devoto, M., Dodge, S., Ellinghaus, E., Fachal, L., Farkkila, M., Faubion, W., Ferreira, M., Franchimont, D., Gabriel, S.B., Ge, T., Georges, M., Gettler, K., Giri, M., Glaser, B., Goerg, S., Goyette, P., Graham, D., Hamalainen, E., Haritunians, T., Heap, G.A., Hiltunen, M., Hoeppner, M., Horowitz, J.E., Irving, P., Iyer, V., Jalas, C., Kelsen, J., Khalili, H., Kirschner, B.S., Kontula, K., Koskela, J.T., Kugathasan, S., Kupcinskas, J., Lamb, C.A., Laudes, M., Levesque, C., Levine, A.P., Lewis, J.D., Liefferinckx, C., Loescher, B.S., Louis, E., Mansfield, J., May, S., McCauley, J.L., Mengesha, E., Mni, M., Moayyedi, P., Moran, C.J., Newberry, R.D., O'Charoen, S., Okou, D.T., Oldenburg, B., Ostrer, H., Palotie, A., Paquette, J., Pekow, J., Peter, I., Pierik, M.J., Ponsioen, C.Y., Pontikos, N., Prescott, N., Pulver, A.E., Rahmouni, S., Rice, D.L., Saavalainen, P., Sands, B., Sartor, R.B., Schiff, E.R., Schreiber, S., Schumm, L.P., Segal, A.W., Seksik, P., Shawky, R., Sheikh, S.Z., Silverberg, M.S., Simmons, A., Skeiceviciene, J., Sokol, H., Solomonson, M., Somineni, H., Sun, D., Targan, S., Turner, D., Uhlig, H.H., Meulen, A.E. van der, Vermeire, S., Verstockt, S., Voskuil, M.D., Winter, H.S., Young, J., Duerr, R.H., Franke, A., Brant, S.R., Cho, J., Weersma, R.K., Parkes, M., Xavier, R.J., Rivas, M.A., Rioux, J.D., McGovern, D.P.B., Huang, H.L., Anderson, C.A., Daly, M.J., Belgium IBD Consortium, Cedars-Sinai IBD, International IBD Genetics Consortium, NIDDK IBD Genetics Consortium, NIHR IBD BioResource, Regeneron Genetics Center, SHARE Consortium, SPARC IBD Network, UK IBD Genetics Consortium, Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), RS: NUTRIM - R2 - Liver and digestive health, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
Crohn Disease, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Article, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.

Published
2022

7. Increased Risk of High-grade Cervical Neoplasia in Women with Inflammatory Bowel Disease:A Case-controlled Cohort Study

Author

Goetgebuer, R.L., Kreijne, J.E., Aitken, C.A., Dijkstra, G., Hoentjen, F., Boer, N.K. de, Oldenburg, B., Meulen, A.E. van der, Ponsioen, C.I.J., Pierik, M.J., Kemenade, F.J. van, Kok, I.M.C.M. de, Siebers, A.G., Mannien, J., Woude, C.J. van der, Vries, A.C. de, Dutch Initiative Crohn Colitis ICC, Gastroenterology and hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Groningen Institute for Organ Transplantation (GIOT), Translational Immunology Groningen (TRIGR), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), RS: NUTRIM - R2 - Liver and digestive health, Gastroenterology & Hepatology, Public Health, and Pathology

Subjects
Uterine Cervical Neoplasms, GUIDELINES, Inflammatory bowel disease, Cohort Studies, 0302 clinical medicine, Risk Factors, INFECTION, Medicine, DYSPLASIA, Prospective cohort study, human papillomavirus, Early Detection of Cancer, Netherlands, ABNORMALITIES, Incidence, Gastroenterology, General Medicine, Middle Aged, CANCER, female genital diseases and pregnancy complications, PREVALENCE, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Female, Immunosuppressive Agents, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Cohort study, Papanicolaou Test, Adult, medicine.medical_specialty, General Population Cohort, Cervical Intraepithelial Neoplasia/diagnosis, cervical intraepithelial neoplasia, Cervical intraepithelial neoplasia, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Uterine Cervical Neoplasms/diagnosis, Internal medicine, MANAGEMENT, Humans, AcademicSubjects/MED00260, Aged, business.industry, HUMAN-PAPILLOMAVIRUS, Original Articles, Odds ratio, Inflammatory Bowel Diseases, Uterine Cervical Dysplasia, medicine.disease, Inflammatory Bowel Diseases/complications, digestive system diseases, Dysplasia, Case-Control Studies, Immunosuppressive Agents/therapeutic use, Patient Compliance, Neoplasm Grading, business, CONSENSUS, RESPONSES
Abstract

Background and Aims Women with inflammatory bowel disease [IBD] may be at higher risk for cervical intraepithelial neoplasia [CIN]. However, data are conflicting. The aim of this study was to assess the risk of high-grade dysplasia and cancer [CIN2+] in IBD women and identify risk factors. Methods Clinical data from adult IBD women in a multicentre Dutch IBD prospective cohort [PSI] from 2007 onwards were linked to cervical cytology and histology records from the Dutch nationwide cytology and pathology database [PALGA], from 2000 to 2016. Patients were frequency-matched 1:4 to a general population cohort. Standardised detection rates [SDR] were calculated for CIN2+. Longitudinal data were assessed to calculate CIN2+ risk during follow-up using incidence rate ratios [IRR] and risk factors were identified in multivariable analysis. Results Cervical records were available from 2098 IBD women [77%] and 8379 in the matched cohort; median follow-up was 13 years. CIN2+ detection rate was higher in the IBD cohort than in the matched cohort (SDR 1.27, 95% confidence interval [CI] 1.05–1.52). Women with IBD had an increased risk of CIN2+ [IRR 1.66, 95% CI 1.21–2.25] and persistent or recurrent CIN during follow-up (odds ratio [OR] 1.89, 95% CI 1.06–3.38). Risk factors for CIN2+ in IBD women were smoking and disease location (ileocolonic [L3] or upper gastrointestinal [GI] [L4]). CIN2+ risk was not associated with exposure to immunosuppressants. Conclusions Women with IBD are at increased risk for CIN2+ lesions. These results underline the importance of human papillomavirus [HPV] vaccination and adherence to cervical cancer screening guidelines in IBD women, regardless of exposure to immunosuppressants.

Published
2021
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8. Vulvar and vaginal neoplasia in women with inflammatory bowel disease

Author

Rouvroye, M.D., Tack, G.J., Mom, C.H., Lissenberg-Witte, B.I., Pierik, M.J., Neefjes-Borst, E.A., Boer, N.K.H. de, Lowenberg, M., Bodelier, A., Verbeek, W.H., Schoon, E., Witteman, E.M., Herwaarden, M.A., Woude, C.J. van der, Lutgens, M., Kouw, E., Veek, P.J. van der, Hulst, R.W. van der, Sipkema, H., Nissen, L.H.C., Bus, P.J., Meulen, A.E. van der, Bruijne, F.H. de, Waaij, L.A. van der, Noomen, C.G., Jharap, B., Schmittgens, S., Jansen, J.M., Hoentjen, F., Lammertink, M.H.A., Houben, G.M.P., Minderhoud, I.M., Dijkstra, G., Oldenburg, B., Sikkens, M.S.G., Tuyl, S.A. van, Bodegraven, A.A. van, Dutch Workgrp IBD Vulvovaginal Neo, Academic Medical Center, Amsterdam Gastroenterology Endocrinology Metabolism, Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), RS: NUTRIM - R2 - Liver and digestive health, Anatomy and neurosciences, Gastroenterology and hepatology, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), Epidemiology and Data Science, Pathology, AGEM - Digestive immunity, Other Research, AII - Inflammatory diseases, APH - Methodology, Groningen Institute for Organ Transplantation (GIOT), Translational Immunology Groningen (TRIGR), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Gastroenterology & Hepatology

Subjects
Inflammatory bowel disease, 0302 clinical medicine, Risk Factors, Epidemiology, EPIDEMIOLOGY, Registries, INCREASED RISK, Netherlands, Vaginal cancer, education.field_of_study, Vulvar Neoplasms, Incidence, Gastroenterology, Middle Aged, CANCER, PREVALENCE, THIOPURINES, Immunosuppressive therapy, 030220 oncology & carcinogenesis, Cohort, SURVIVAL, Female, 030211 gastroenterology & hepatology, FEMALE GENITAL-TRACT, Carcinoma in Situ, Immunosuppressive Agents, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Adult, medicine.medical_specialty, Vaginal Neoplasms, Adolescent, Population, Malignancy, Young Adult, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Internal medicine, Journal Article, medicine, Humans, COHORT, Medical history, education, Aged, Retrospective Studies, Hepatology, business.industry, HUMAN-PAPILLOMAVIRUS, Cancer, Inflammatory Bowel Diseases, medicine.disease, TRENDS, Vulvar or vaginal malignancy, Neoplasm Recurrence, Local, business
Abstract

Immunosuppressive drugs are the cornerstone in the treatment of inflammatory bowel disease (IBD), however they are associated with an increased risk of extra-intestinal cancer. Whether the risk for female genital tract malignancies, including vulvar and vaginal cancer, is increased is less clear.Our aim was to investigate the risk of these malignancies in IBD-patients.Histopathological data of all IBD patients with a vulvar or vaginal (pre-)cancerous lesion were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology from 1991 to 2015. Medical history was retrieved from patient records. Data from the Central Office for Statistics, the Dutch comprehensive cancer organization, and the IBDSL cohort were obtained to calculate the standardized, and age-adjusted incidence rates.Fifty-five patients met the inclusion criteria. A standardized incidence rate of 1.2(95% CI:0.8-1.7) for vulvar and vaginal carcinoma among adult female IBD was calculated, which did not significantly differ from the general population. The use of immunosuppressive therapy did not increase the occurrence of vulvovaginal malignancy, nor did it influence the recurrence rate. However, immunosuppressive drugs ever-users were on average 11 years younger at the time of their gynaecological diagnosis.Overall, our data do not support intensified screening for vulvar or vaginal malignancies in female IBD patients. (C) 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Published
2020
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9. Decreasing Trends in Intestinal Resection and Re-Resection in Crohn's Disease A Nationwide Cohort Study

Author

Beelen, E.M.J., Woude, C.J. van der, Pierik, M.J., Hoentjen, F., Boer, N.K. de, Oldenburg, B., Meulen, A.E. van der, Ponsioen, C.I.J., Dijkstra, G., Bruggink, A.H., Erler, N.S., Schouten, W.R., Vries, A.C. de, Dutch Initiative Crohn's Colitis, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Maag Darm Lever (9), Interne Geneeskunde, Gastroenterology and hepatology, AGEM - Digestive immunity, AII - Infectious diseases, Gastroenterology & Hepatology, Epidemiology, and Surgery

Subjects
Adult, Male, medicine.medical_specialty, Lower risk, Gastroenterology, Inflammatory bowel disease, Cohort Studies, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, Crohn Disease, inflammatory bowel disease, Internal medicine, Humans, ileocecal resection, Medicine, Registries, Practice Patterns, Physicians', Netherlands, time trends, Crohn's disease, business.industry, Proportional hazards model, Hazard ratio, medicine.disease, Confidence interval, 030220 oncology & carcinogenesis, Cohort, Female, 030211 gastroenterology & hepatology, Surgery, business, Colorectal Surgery, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Cohort study
Abstract

OBJECTIVE: To assess time trends in intestinal resection and re-resection in Crohn's disease (CD) patients. SUMMARY OF BACKGROUND DATA: CD treatment has changed considerably over the past decades. The effect of these advances on the necessity of intestinal resections and the risk of re-resection is unclear. METHODS: In this nationwide cohort study, adult CD patients with ileocolonic, small bowel, colon, or rectum resections between 1991 and 2015 were included. Data were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology (PALGA). Time trends were analyzed with a broken stick model and Cox proportional hazard model with smoothing splines. RESULTS: The identified cohort comprised 8172 CD patients (3293/4879 male/female) in whom 10,315 intestinal resections were performed. The annual intestinal resection rate decreased nonlinearly from 22.7/100,000 CD patients (1991) to 2.5/100,000 (2015). A significantly steeper decrease was observed before 1999 (slope -1.56) as compared to subsequent years (slope -0.41) (P < 0.001). Analogous trends were observed for ileocolonic, small bowel, and colon resections. Overall cumulative risk of re-resection was 10.9% at 5 years, 18.6% at 10 years, and 28.3% at 20 years after intestinal resection. The hazard for intestinal re-resection showed a nonlinear decreasing trend, with hazard ratio 0.39 (95% confidence interval 0.36-0.44) in 2000 and hazard ratio 0.25 (95% confidence interval 0.18-0.34) in 2015 as compared to 1991. CONCLUSION: Over the past 25 years, intestinal resection rate has decreased significantly for ileocolonic, small bowel, and colonic CD. In addition, current postoperative CD patients are at 75% lower risk of intestinal re-resection.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

Published
2021
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10. Increased Risk of High-grade Cervical Neoplasia in Women with Inflammatory Bowel Disease: A Case-controlled Cohort Study

Author

Goetgebuer, R.L., Kreijne, J.E., Aitken, C.A., Dijkstra, G., Hoentjen, F., Boer, N.K. de, Oldenburg, B., Meulen, A.E. van der, Ponsioen, C.I., Pierik, M.J., Kemenade, F.J. van, Kok, I., Siebers, A.G., Manniën, J., Woude, C.J. van der, Vries, A.C.M. de, Goetgebuer, R.L., Kreijne, J.E., Aitken, C.A., Dijkstra, G., Hoentjen, F., Boer, N.K. de, Oldenburg, B., Meulen, A.E. van der, Ponsioen, C.I., Pierik, M.J., Kemenade, F.J. van, Kok, I., Siebers, A.G., Manniën, J., Woude, C.J. van der, and Vries, A.C.M. de

Abstract

Item does not contain fulltext, BACKGROUND AND AIMS: Women with inflammatory bowel disease [IBD] may be at higher risk for cervical intraepithelial neoplasia [CIN]. However, data are conflicting. The aim of this study was to assess the risk of high-grade dysplasia and cancer [CIN2+] in IBD women and identify risk factors. METHODS: Clinical data from adult IBD women in a multicentre Dutch IBD prospective cohort [PSI] from 2007 onwards were linked to cervical cytology and histology records from the Dutch nationwide cytology and pathology database [PALGA], from 2000 to 2016. Patients were frequency-matched 1:4 to a general population cohort. Standardised detection rates [SDR] were calculated for CIN2+. Longitudinal data were assessed to calculate CIN2+ risk during follow-up using incidence rate ratios [IRR] and risk factors were identified in multivariable analysis. RESULTS: Cervical records were available from 2098 IBD women [77%] and 8379 in the matched cohort; median follow-up was 13 years. CIN2+ detection rate was higher in the IBD cohort than in the matched cohort (SDR 1.27, 95% confidence interval [CI] 1.05-1.52). Women with IBD had an increased risk of CIN2+ [IRR 1.66, 95% CI 1.21-2.25] and persistent or recurrent CIN during follow-up (odds ratio [OR] 1.89, 95% CI 1.06-3.38). Risk factors for CIN2+ in IBD women were smoking and disease location (ileocolonic [L3] or upper gastrointestinal [GI] [L4]). CIN2+ risk was not associated with exposure to immunosuppressants. CONCLUSIONS: Women with IBD are at increased risk for CIN2+ lesions. These results underline the importance of human papillomavirus [HPV] vaccination and adherence to cervical cancer screening guidelines in IBD women, regardless of exposure to immunosuppressants.

Published
2021

11. Methotrexate and Thioguanine Rescue Therapy for Conventional Thiopurine Failing Ulcerative Colitis Patients: A Multi-center Database Study on Tolerability and Effectiveness

Author

Meijer, B., Mulder, C.J.J., Bouma, G., Ponsioen, C.Y., Woude, C.J. van der, Meulen, A.E. van der, Wintjens, D.S.J., Dijkstra, G., Hoentjen, F., Oldenburg, B., Bodegraven, A.A. van, Boer, N.K.H. de, Dutch Initiative Crohn Colitis ICC, Translational Immunology Groningen (TRIGR), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Gastroenterology & Hepatology, Gastroenterology and hepatology, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, AII - Inflammatory diseases, Amsterdam Reproduction & Development (AR&D), Promovendi NTM, Interne Geneeskunde, RS: NUTRIM - R2 - Liver and digestive health, Gastroenterology and Hepatology, and AGEM - Endocrinology, metabolism and nutrition

Subjects
Male, Databases, Factual, NODULAR REGENERATIVE HYPERPLASIA, 6-THIOGUANINE, Inflammatory bowel disease, 0302 clinical medicine, Immunology and Allergy, Prospective Studies, 030212 general & internal medicine, Netherlands, Thiopurine methyltransferase, biology, Remission Induction, Gastroenterology, Drug Tolerance, Middle Aged, Ulcerative colitis, CROHNS-DISEASE, PREVALENCE, Treatment Outcome, Tolerability, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, INTERCEPT COHORTS, Immunosuppressive Agents, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], medicine.drug, Adult, medicine.medical_specialty, methotrexate, 03 medical and health sciences, Pharmacotherapy, inflammatory bowel disease, Internal medicine, thioguanine, INFLIXIMAB, medicine, Humans, Adverse effect, Proportional Hazards Models, ulcerative colitis, business.industry, thiopurines, medicine.disease, EFFICACY, Infliximab, rescue therapy, biology.protein, Colitis, Ulcerative, Methotrexate, business, CONSENSUS, MEDICAL-MANAGEMENT, INFLAMMATORY-BOWEL-DISEASE
Abstract

Item does not contain fulltext Background: Patients with active ulcerative colitis (UC) failing conventional therapies are in need of rescue strategies. Due to the fact that accepted step-up therapy with biologicals is expensive and sometimes unavailable, alternative therapies are warranted. Methotrexate (MTX) and thioguanine (TG) have both been suggested as alternative maintenance strategies in conventional thiopurine failing UC patients. In this multicenter database study, we compared safety and effectiveness (drug-survival) of MTX and TG in UC patients. Methods: We collected data from the Parelsnoer database, a prospective Dutch national database consisting of inflammatory bowel disease patients from all university hospitals in The Netherlands. Additional data were collected from detailed chart review. Results: In total, 99 UC patients were included, of which 48 used TG, 43 used MTX, and 8 patients had a history of both TG and MTX use. In 12% of the patients, biological therapy had failed. Roughly 70% of the patients in both groups were able to continue therapy for over 1 year. Adverse events were noted in 33% of all the patients and were mainly elevated liver enzymes or gastrointestinal complaints. Twenty-eight patients (28%) continued therapy (15 TG, 13 MTX) without the need of escalation therapy (eg, corticosteroids, biologicals, or surgery). Drug survival curves of both drugs were comparable, just as the number of patients with sustained clinical benefit of therapy (P > 0.05). Conclusion: Both MTX and TG may be used and maintained as rescue therapy with sustained clinical benefit in one-third of the UC patients failing conventional therapies.

Published
2018
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12. Off-label prescriptions of drugs used for the treatment of Crohn’s disease or ulcerative colitis

Author

Simsek, M., Lissenberg-Witte, B.I., Riswijk, M.L.M. van, Verschuren, S., Hoentjen, F., Oldenburg, B., Ponsioen, C.Y., Woude, C.J. van der, Meulen, A.E. van der, Pierik, M., Dijkstra, G., Boer, N.K.H. de, Parelsnoer Inst PSI, Dutch Initiative Crohns Colitis, Gastroenterology and hepatology, Epidemiology and Data Science, APH - Methodology, AGEM - Digestive immunity, AII - Inflammatory diseases, Amsterdam Reproduction & Development (AR&D), AGEM - Endocrinology, metabolism and nutrition, Gastroenterology and Hepatology, Gastroenterology & Hepatology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Groningen Institute for Organ Transplantation (GIOT), Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), and RS: NUTRIM - R2 - Liver and digestive health

Subjects
Crohn’s disease, Male, Databases, Factual, Off-label use, Inflammatory bowel disease, drugs, off-label, 0302 clinical medicine, Crohn Disease, Pharmacology (medical), 030212 general & internal medicine, media_common, Netherlands, Crohn's disease, Mercaptopurine, Gastroenterology, Beclomethasone, Ulcerative colitis, prescriptions, Off‐label Drug Prescribing in Inflammatory Bowel Disease, 030211 gastroenterology & hepatology, Original Article, off‐label, Female, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], medicine.drug, Drug, Adult, medicine.medical_specialty, Adolescent, media_common.quotation_subject, Allopurinol, therapeutic care, 03 medical and health sciences, Young Adult, All institutes and research themes of the Radboud University Medical Center, inflammatory bowel disease, Internal medicine, medicine, Journal Article, Humans, Medical prescription, Thioguanine, ulcerative colitis, Tofacitinib, Hepatology, business.industry, Off-Label Use, medicine.disease, digestive system diseases, Methotrexate, Colitis, Ulcerative, business
Abstract

BACKGROUND: Off-label prescribing is encountered across various fields of medicine and creates alternative treatment options, but is associated with unknown safety risks. The use of off-label drugs for the treatment of patients with inflammatory bowel diseases (IBD) has not been characterised before.AIM: To assess the proportion and characteristics of off-label prescribing for IBD in tertiary care centres in the Netherlands.METHODS: A prospective database of IBD patients from all Dutch university hospitals was used to collect data on drug prescriptions for IBD and demographics. Drugs were classified as off-label if they were unlicensed for Crohn's disease and/or ulcerative colitis by the Medicines Evaluation Board. Uni- and multivariable analyses were used to identify patient-specific characteristics predictive of increased off-label use.RESULTS: For the induction and/or maintenance treatment of 4583 IBD patients, 12 651 historical and current drug records were available in the database. Of these, 2374 (19%) were considered off-label prescriptions. Out of 4583 IBD patients, 1477 (32%) were exposed to off-label drugs. Commonly prescribed off-label IBD drugs were mercaptopurine (18%), beclomethasone (12%), thioguanine (4%) and allopurinol (3%). Non-thiopurine/methotrexate off-label drugs were prescribed in 243 patients (6%), including biological agents or tofacitinib in 47 IBD patients (1%). Off-label prescriptions were more common in ulcerative colitis than Crohn's disease (37% vs 29%, P < 0.001). Smokers and patients that received ≥5 drug types during their disease course were more likely to be exposed to off-label drugs (smoking 33% vs 27% and multiple drug use 66% vs 22%, both P < 0.001).CONCLUSION: About one-fifth of prescriptions for IBD were off-label and one-third of IBD patients, especially ulcerative colitis patients, were exposed to off-label drugs.

Published
2019
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13. Clinical Course of Nodular Regenerative Hyperplasia in Thiopurine Treated Inflammatory Bowel Disease Patients

Author

Simsek, M., Meijer, B., Ramsoekh, D., Bouma, G., Wouden, E.J. van der, Hartog, B. den, Vries, A.C.M. de, Hoentjen, F., Dijkstra, G., Boer, Sybrand Y. de, Jansen, J.M, Meulen, A.E. van der, Beukers, R., Brink, M.A., Steinhauser, T., Oldenburg, B., Gilissen, L.P., Naber, T.H., Verhagen, M.A., Boer, N.K. de, Mulder, C.J., Simsek, M., Meijer, B., Ramsoekh, D., Bouma, G., Wouden, E.J. van der, Hartog, B. den, Vries, A.C.M. de, Hoentjen, F., Dijkstra, G., Boer, Sybrand Y. de, Jansen, J.M, Meulen, A.E. van der, Beukers, R., Brink, M.A., Steinhauser, T., Oldenburg, B., Gilissen, L.P., Naber, T.H., Verhagen, M.A., Boer, N.K. de, and Mulder, C.J.

Abstract

Item does not contain fulltext, Nodular regenerative hyperplasia (NRH) is a poorly understood liver condition, which is increasingly recognized in thiopurine-treated patients with inflammatory bowel disease (IBD).(1) It is difficult to establish an optimal approach to NRH patients, because its manifestations are highly variable (from asymptomatic to symptoms of noncirrhotic portal hypertension [NCPH]) and the prognosis is unknown.(2) The aim of this study was to identify NRH cases in IBD patients treated with azathioprine, mercaptopurine, and/or thioguanine, and to describe its clinical course.

Published
2019

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