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Siegel, C. A., Whitman, C. B., Spiegel, B. M. R., Feagan, B., Sands, B., Loftus, E. V., . . . Peyrin-Biroulet, L. (2018). Development of an index to define overall disease severity in IBD. Gut, 67(2), 244-254.
Open this publication in new window or tab >>Development of an index to define overall disease severity in IBD
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2018 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 2, 244-254 p.Article in journal (Refereed) Published
Abstract [en]

Background and aim: Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC.

Methods: Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute.

Results: For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities.

Conclusions: Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.

Place, publisher, year, edition, pages
London, United Kingdom: BMJ Publishing Group Ltd, 2018
Keyword
Crohn's Disease, IBD, Ulcerative Colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-53356 (URN)10.1136/gutjnl-2016-312648 (DOI)000419604800009 ()27780886 (PubMedID)
Note

Funding Agencies:

AbbVie  

Tillotts 

Available from: 2016-11-02 Created: 2016-11-02 Last updated: 2018-01-19Bibliographically approved
Eriksson, C., Rundquist, S., Lykiardopoulos, B., Karlén, P., Grip, O., Söderman, C., . . . Halfvarson, J. (2017). A Swedish observational study (SVEAH) on vedolizumab assessing effectiveness and healthcare resource utilization in patients with inflammatory bowel disease. Journal of Crohn's & Colitis, 11(Suppl. 1), S262-S263.
Open this publication in new window or tab >>A Swedish observational study (SVEAH) on vedolizumab assessing effectiveness and healthcare resource utilization in patients with inflammatory bowel disease
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2017 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no Suppl. 1, S262-S263 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Oxford University Press, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-57782 (URN)10.1093/ecco-jcc/jjx002.489 (DOI)000398606900471 ()28172603 (PubMedID)
Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2017-10-18Bibliographically approved
Kuja-Halkola, R., Lebwohl, B., Halfvarson, J., Emilsson, L., Magnusson, P. K. & Ludvigsson, J. F. (2017). Birth weight, sex, and celiac disease: a nationwide twin study. Clinical Epidemiology, 9, 567-577.
Open this publication in new window or tab >>Birth weight, sex, and celiac disease: a nationwide twin study
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2017 (English)In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 9, 567-577 p.Article in journal (Refereed) Published
Abstract [en]

Objective: Earlier research suggests that birth weight may be associated with celiac disease (CD), but the direction of association has been unclear potentially due to confounding effect from genetic and intrafamilial factors. Through within-twin analyses, we aimed to minimize confounding effects such as twins that share genetic and early environmental exposures.

Materials and methods: Using the Swedish Twin Registry, we examined the birth weight of 146,830 twins according to the CD status. CD was defined as having villous atrophy according to a small intestinal biopsy reports.

Results: The prevalence of diagnosed CD was 0.5% (n=669), and we included 407 discordant pairs of CD-non-CD twins. Comparing the 669 CD patients with non-CD twins, the association between birth weight and future CD was not statistically significant (odds ratio [OR] per 1000 g increase in birth weight: 1.16; 95% confidence interval [CI]=0.97-1.38). In males, the association was positive and statistically significant (OR=1.50; 95% CI=1.11-2.02). However, the association was not significant in within-pair analyses for both dizygotic and monozygotic twins and for both sexes.

Conclusion: This population-based study found that in male twins, higher birth weight was associated with higher risk of CD. However, when comparing discordant twin pairs in within-twin pair analyses, there was no statistically significant association between birth weight, intrauterine growth, and future risk of CD.

Place, publisher, year, edition, pages
DOVE Medical Press Ltd., 2017
Keyword
autoimmune, gestational age, gluten, registries, risk factors, twins
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:oru:diva-62848 (URN)10.2147/CLEP.S149181 (DOI)000414865700001 ()
Funder
Swedish Society of MedicineSwedish Research Council
Available from: 2017-11-27 Created: 2017-11-27 Last updated: 2017-11-29Bibliographically approved
Burisch, J., Halfvarson, J., Kupcinskas, L., Hernandez, V., Kaimakliotis, I., Valpiani, D., . . . Munkholm, P. (2017). Change in Crohn's disease behavior in a prospective European population-based inception cohort - the ECCO-EpiCom cohort. Journal of Crohn's & Colitis, 11(Suppl. 1), S452-S453.
Open this publication in new window or tab >>Change in Crohn's disease behavior in a prospective European population-based inception cohort - the ECCO-EpiCom cohort
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2017 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no Suppl. 1, S452-S453 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Oxford University Press, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-57779 (URN)10.1093/ecco-jcc/jjx002.851 (DOI)000398606901261 ()28175198 (PubMedID)
Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2017-10-18Bibliographically approved
Eriksson, C., Cao, Y., Rundquist, S., Zhulina, Y., Henriksson, I., Montgomery, S. & Halfvarson, J. (2017). Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Orebro, Sweden, 1963-2010. Alimentary Pharmacology and Therapeutics, 46(8), 748-757.
Open this publication in new window or tab >>Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Orebro, Sweden, 1963-2010
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2017 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 46, no 8, 748-757 p.Article in journal (Refereed) Published
Abstract [en]

Background: Whether the epidemiology of ulcerative colitis (UC) has changed during recent decades is partly unknown.

Aim: To depict temporal trends in the epidemiology and medical treatment of UC as well as the long-term risk of progression in disease extent and colectomy, during 1963-2010.

Methods: Patients were identified by evaluation of all medical records in the archive of the Colitis Clinic, Orebro University Hospital. Comparisons were made between three time periods, 1963-1975, 1976-1990 and 1991-2005.

Results: The annual age-standardised incidence increased from 3.5 to 18.5 per 100 000 during the study period (P < .01). Correspondingly, the prevalence increased from 44 to 474 per 100 000 between 1965 and 2010. A higher proportion of males than females had extensive colitis at diagnosis (odds ratio: 1.55; 95% CI 1.17-2.05; P < .01). The risk for progression in disease extent was 34.5% and 18.5% at 10 years, for patients with proctitis and left-sided colitis, respectively (P < .01). The use of 5-aminosalicylates, within 10 years, rise from 79% to 92% between 1963-1975 and 1976-1990 (P < .01). Thiopurine use increased from 7% in 1976-1990 to 34% during 1991-2005 (P < .01). The colectomy rate at 10 years was 13.5% (95% CI 11.1%-15.8%), and the risk was lower among patients diagnosed in 1991-2005 compared to 1963-1975 (adjusted hazard ratio: 0.61; 95% CI 0.39-0.94; P = .02).

Conclusion: The incidence and prevalence of UC increased over time, and the observed prevalence in 2010 is among the highest reported. In parallel, a decrease in colectomy rates was observed during the most recent decades, potentially reflecting improved medical treatment.

Place, publisher, year, edition, pages
Hoboken, USA: John Wiley & Sons, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-61349 (URN)10.1111/apt.14268 (DOI)000411717800005 ()28833287 (PubMedID)2-s2.0-85029232492 (Scopus ID)
Note

Funding Agency:

Swedish Government's Agreement for Medical Training and Research  OLL-549221

Available from: 2017-10-09 Created: 2017-10-09 Last updated: 2017-11-27Bibliographically approved
Amcoff, K., Stridsberg, M., Lampinen, M., Magnuson, A., Carlson, M. & Halfvarson, J. (2017). Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time. Scandinavian Journal of Gastroenterology, 52(3), 344-350.
Open this publication in new window or tab >>Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time
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2017 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, 344-350 p.Article in journal (Refereed) Published
Abstract [en]

Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.

Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Bühlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).

Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Bühlmann 845 (1061-226) μg/g versus 62 (224-39) μg/g, Phadia 369 (975-122) μg/g versus 11 (52-11) μg/g, and Immundiagnostik 135 (302-69) μg/g versus 8 (56-4) μg/g. The Bühlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Bühlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50 μg/g was used, whereas the differences in sensitivity were less pronounced.

Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.

Place, publisher, year, edition, pages
Oxon, United Kingdom: Taylor & Francis, 2017
Keyword
Biomarker, Crohn's disease, faecal calprotectin, inflammatory bowel, disease, ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-53665 (URN)10.1080/00365521.2016.1256424 (DOI)000392488800015 ()27881032 (PubMedID)2-s2.0-84996799488 (Scopus ID)
Funder
Swedish Research Council, 521-2011-2764
Note

Funding Agencies:

Örebro University Hospital Research Foundation OLL-333321

Uppsala-Örebro Regional Research Foundation RFR-314671

Available from: 2016-11-28 Created: 2016-11-28 Last updated: 2018-01-11Bibliographically approved
Rencz, F., Gulácsi, L., Péntek, M., Gecse, K. B., Dignass, A., Halfvarson, J., . . . Brodszky, V. (2017). Cost-utility of biological treatment sequences for luminal Crohn's disease in Europe. Expert review of pharmacoeconomics & outcomes research, 17(6), 597-606.
Open this publication in new window or tab >>Cost-utility of biological treatment sequences for luminal Crohn's disease in Europe
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2017 (English)In: Expert review of pharmacoeconomics & outcomes research, ISSN 1473-7167, E-ISSN 1744-8379, Vol. 17, no 6, 597-606 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: This study aims to compare the cost-effectiveness of treatment sequences with available biologics, including adalimumab (ADA), biosimilar infliximab (bsIFX), originator infliximab (IFX) and vedolizumab (VEDO) for luminal Crohn's disease in nine European countries.

METHODS: A Markov-model was constructed to simulate five-year medical costs and quality-adjusted life years (QALYs). Data on clinical efficacy were obtained from randomised controlled trials. Country-specific unit costs, discount rates and a third-party payer perspective were applied.

RESULTS: The bsIFX versus conventional therapy resulted in the most favourable incremental cost-utility ratios (ICURs) ranging from €34,580 (Hungary) to €77,062/QALY (Sweden). Compared to bsIFX, the bsIFX-ADA sequence was more cost-effective than the bsIFX-VEDO sequence with ICURs varying between €70,277 (France) and €162,069/QALY (Germany). The ICURs of the bsIFX-ADA-VEDO sequence versus the bsIFX-ADA strategy were between €206,266 (The Netherlands) and €363,232/QALY (Spain).

CONCLUSION: We are the first to compare cost-effectiveness of multiple biological sequences for luminal Crohn's disease. Based on our findings, bsIFX can be recommended as a first-line treatment in patients unresponsive to conventional treatments. While biological sequences only slightly differ in their associated health gains, their costs vary greatly. The bsIFX-ADA-VEDO seems to be the most cost-effective sequence of the available biologics across Europe.

Place, publisher, year, edition, pages
Taylor & Francis, 2017
Keyword
Adalimumab, biosimilar infliximab, cost-effectiveness, Crohn's disease, inflammatory bowel diseases; infliximab, vedolizumab
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:oru:diva-60913 (URN)10.1080/14737167.2017.1322509 (DOI)000415840300010 ()28434387 (PubMedID)2-s2.0-85018171573 (Scopus ID)
Note

Funding Agency:

Pfizer Hospira UK Ltd

Available from: 2017-09-18 Created: 2017-09-18 Last updated: 2017-12-07Bibliographically approved
Burisch, J., Halfvarson, J., Kupcinskas, L., Hernandez, V., Kaimakliotis, I., Valpiani, D., . . . Munkholm, P. (2017). Disease course during the first five years following diagnosis in a prospective European population-based inception cohort - the ECCO-EpiCom cohort. Journal of Crohn's & Colitis, 11(Suppl. 1), S435-S436.
Open this publication in new window or tab >>Disease course during the first five years following diagnosis in a prospective European population-based inception cohort - the ECCO-EpiCom cohort
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2017 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no Suppl. 1, S435-S436 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Oxford University Press, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-57781 (URN)10.1093/ecco-jcc/jjx002.818 (DOI)000398606901228 ()28172943 (PubMedID)
Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2017-10-18Bibliographically approved
Halfvarson, J., Brislawn, C. J., Lamendella, R., Vázquez-Baeza, Y., Walters, W. A., Bramer, L. M., . . . Jansson, J. K. (2017). Dynamics of the human gut microbiome in inflammatory bowel disease. Nature microbiology, 2(5), Article ID 17004.
Open this publication in new window or tab >>Dynamics of the human gut microbiome in inflammatory bowel disease
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2017 (English)In: Nature microbiology, ISSN 2058-5276, Vol. 2, no 5, 17004Article in journal (Refereed) Published
Abstract [en]

Inflammatory bowel disease (IBD) is characterized by flares of inflammation with a periodic need for increased medication and sometimes even surgery. The aetiology of IBD is partly attributed to a deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD subtypes, including ulcerative colitis, colonic Crohn's disease and ileal Crohn's disease. Although IBD is dynamic, microbiome studies have primarily focused on single time points or a few individuals. Here, we dissect the long-term dynamic behaviour of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than those of healthy individuals, based on deviation from a newly defined healthy plane (HP). Ileal Crohn's disease subjects deviated most from the HP, especially subjects with surgical resection. Intriguingly, the microbiomes of some IBD subjects periodically visited the HP then deviated away from it. Inflammation was not directly correlated with distance to the healthy plane, but there was some correlation between observed dramatic fluctuations in the gut microbiome and intensified medication due to a flare of the disease. These results will help guide therapies that will redirect the gut microbiome towards a healthy state and maintain remission in IBD.

Place, publisher, year, edition, pages
London, United Kingdom: Nature Publishing Group, 2017
National Category
Microbiology in the medical area
Research subject
Microbiology
Identifiers
urn:nbn:se:oru:diva-55696 (URN)10.1038/nmicrobiol.2017.4 (DOI)000404894200015 ()28191884 (PubMedID)2-s2.0-85012903225 (Scopus ID)
Funder
Swedish Foundation for Strategic Research , RB13-0160Swedish Research Council, 521-2011-2764
Note

Funding Agencies:

United States National Institutes of Health  NIH IU54DE023798-01 

Pacific Northwest National Laboratory  DE-AC05-76RLO1830 

Crohn's and Colitis Foundation of America  

Örebro University Hospital Research Foundation  OLL-507001 

Howard Hughes Medical Institute through the Precollege and Undergraduate Science Education Program  

National Science Foundation (NSF)  DBI-1248096 

Available from: 2017-02-15 Created: 2017-02-15 Last updated: 2018-01-13Bibliographically approved
Eriksson, C., Cao, Y., Rundquist, S., Zhulina, Y., Henriksson, I., Montgomery, S. & Halfvarson, J. (2017). Editorial: do thiopurines and biologics decrease the risk of colectomy? Authors' reply. Alimentary Pharmacology and Therapeutics, 46(9), 897-898.
Open this publication in new window or tab >>Editorial: do thiopurines and biologics decrease the risk of colectomy? Authors' reply
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2017 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 46, no 9, 897-898 p.Article in journal, Editorial material (Other academic) Published
National Category
Gastroenterology and Hepatology Pharmacology and Toxicology
Identifiers
urn:nbn:se:oru:diva-61920 (URN)10.1111/apt.14336 (DOI)000412754500018 ()29023888 (PubMedID)2-s2.0-85030863815 (Scopus ID)
Available from: 2017-10-24 Created: 2017-10-24 Last updated: 2018-01-13Bibliographically approved
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