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Epidemiological and therapeutic aspects of Inflammatory Bowel Disease
Örebro University, School of Medical Sciences.ORCID iD: 0000-0002-1046-383x
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: The two main forms of inflammatory bowel disease (IBD) are Crohn’s disease and ulcerative colitis. These are chronic inflammatory disorders, mainly affecting the gastrointestinal tract.

Aims: The overall aims of this thesis were to study the epidemiology of ulcerative colitis in Örebro, Sweden; to examine certain aspects of anaemia in IBD; and to determine the clinical effectiveness of medical treatments.

Material and methods: Cohort studies with the sampling frame defined by the geographic boundaries of the primary catchment area of Örebro University Hospital (Papers I‒III), or by the entire IBD population in Sweden registered in the Swedish national quality registry for IBD (SWIBREG; paper IV), were performed to determine the epidemiology of ulcerative colitis, the incidence and prevalence of anaemia in IBD, and the clinical effectiveness of thiopurine drugs and vedolizumab in routine care.

Results: A fivefold increase in the incidence and a tenfold increase in the prevalence of ulcerative colitis was observed in Örebro during the past 50 years. In parallel, the prognosis, in terms of risk for colectomy within 10 years from diagnosis, improved during the same time period. Earlier and more widespread use of thiopurine drugs may have contributed to the decrease in colectomies. Anaemia is common in IBD, particularly in Crohn’s disease. Vedolizumab, a new drug targeting leucocyte migration to the gut, appears to be well tolerated and effective in Swedish real-world IBD care.

Conclusion: Ulcerative colitis is on the rise, and data from Örebro indicate that the number of IBD patients in Sweden already exceeds 70,000. Improved knowledge of long-term outcomes of medical therapy may have far-reaching implications for future IBD management.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2018. , p. 99
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 178
Keywords [en]
Inflammatory bowel disease, ulcerative colitis, Crohn’s disease, cohort study, population-based, colectomy, disease course, anaemia, azathioprine, 6-mercaptopurine, vedolizumab
National Category
General Practice Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-65419ISBN: 978-91-7529-242-7 (print)OAI: oai:DiVA.org:oru-65419DiVA, id: diva2:1186996
Public defence
2018-05-09, Örebro universitet, Campus USÖ, hörsal C2, Södra Grev Rosengatan 32, Örebro, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2018-03-02 Created: 2018-03-02 Last updated: 2018-08-07Bibliographically approved
List of papers
1. 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
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, p. 748-757Article 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: 2018-08-06Bibliographically approved
2. Incidence, prevalence, and clinical outcome of anaemia in inflammatory bowel disease: A population-based cohort study
Open this publication in new window or tab >>Incidence, prevalence, and clinical outcome of anaemia in inflammatory bowel disease: A population-based cohort study
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(English)Manuscript (preprint) (Other academic)
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-66679 (URN)
Available from: 2018-04-19 Created: 2018-04-19 Last updated: 2018-04-19Bibliographically approved
3. Impact of thiopurines on the natural history and surgical outcome of ulcerative colitis: a cohort study
Open this publication in new window or tab >>Impact of thiopurines on the natural history and surgical outcome of ulcerative colitis: a cohort study
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2018 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, article id gutjnl-2017-315521Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: Thiopurines are used as maintenance therapy in ulcerative colitis (UC), but whether these drugs influence the natural history of the disease is unknown. We aimed to assess the effect of thiopurines in terms of colectomy, hospital admission, progression in disease extent and anti-tumour necrosis factor (TNF) therapy within 10 years from initiation.

DESIGN: Patients diagnosed with UC within the Örebro University Hospital catchment area, during 1963-2010, who initiated thiopurines (n=253) were included. To overcome the risk of confounding by indication, we compared patients who stopped treatment within 12 months because of an adverse reaction (n=76) with patients who continued therapy or discontinued due to other reasons (n=177) and assessed long-term outcomes using Cox regression with adjustment for potential confounding factors.

RESULTS: The cumulative probability of colectomy within 10 years was 19.5% in tolerant patients compared with 29.0% in intolerant (adjusted HR 0.49; 95% CI 0.21 to 0.73). The probability of hospital admission was 34.0% in tolerant versus 56.2% in intolerant patients (adjusted HR 0.36; 95% CI 0.23 to 0.56). The risk for progression in disease extent was 20.4% in tolerant patients compared with 48.8% in intolerant (adjusted HR 0.47; 95% CI 0.21 to 1.06). Within 10 years, 16.1% of tolerant and 27.5% of intolerant patients received anti-TNF therapy (adjusted HR 0.49; 95% CI 0.26 to 0.92).

CONCLUSION: Based on the novel approach of comparing patients tolerant and intolerant to thiopurines, we reveal that thiopurines have a profound beneficial impact of the natural history and long-term colectomy rates of UC.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018
Keywords
6-mercaptopurine, azathioprine, chronic ulcerative colitis, tnf-alpha
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-66417 (URN)10.1136/gutjnl-2017-315521 (DOI)29618498 (PubMedID)
Available from: 2018-04-09 Created: 2018-04-09 Last updated: 2018-07-19Bibliographically approved
4. Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)
Open this publication in new window or tab >>Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)
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2017 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 6-7, p. 722-729Article in journal (Refereed) Published
Abstract [en]

Objectives: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness.

Materials and methods: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index<5 in Crohn's disease (CD) and Patient Simple Clinical Colitis Activity index<3 in ulcerative colitis (UC).

Results: Two-hundred forty-six patients (147CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone1 surgical resection. After a median follow-up of 17 (IQR: 14-20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p<.0001 in both groups). Faecal-calprotectin decreased in CD (p<.0001) and in UC (p=.001), whereas CRP decreased in CD (p=.002) but not in UC (p=.11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96-16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10-4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16-6.48).

Conclusion: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.

Place, publisher, year, edition, pages
Taylor & Francis, 2017
Keywords
Vedolizumab, clinical practice, inflammatory bowel disease, Crohn's disease, ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-57787 (URN)10.1080/00365521.2017.1304987 (DOI)000399808100018 ()28362144 (PubMedID)2-s2.0-85018512957 (Scopus ID)
Note

Funding Agencies:

Swedish Government  OLL-549221  OLL-526131  ALFSKANE-539811 

Hedlund Foundation  

Österlund Foundation  

Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2018-07-31Bibliographically approved

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