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Impact of thiopurines on the natural history and surgical outcome of ulcerative colitis: a cohort study
Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.ORCID iD: 0000-0002-1046-383x
Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.ORCID iD: 0000-0002-4923-3169
Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. (Clinical Epidemiology and Biostatistics)ORCID iD: 0000-0002-3552-9153
Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK. (Clinical Epidemiology and Biostatistics)ORCID iD: 0000-0001-6328-5494
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2019 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 4, p. 623-632Article in journal (Refereed) Published
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, 2019. Vol. 68, no 4, p. 623-632
Keywords [en]
6-mercaptopurine, azathioprine, chronic ulcerative colitis, tnf-alpha
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-66417DOI: 10.1136/gutjnl-2017-315521ISI: 000471830300008PubMedID: 29618498Scopus ID: 2-s2.0-85062170737OAI: oai:DiVA.org:oru-66417DiVA, id: diva2:1196118
Note

Funding Agency:

Swedish government's agreement on medical training and research  OLL-549221

Available from: 2018-04-09 Created: 2018-04-09 Last updated: 2019-07-22Bibliographically approved
In thesis
1. Epidemiological and therapeutic aspects of Inflammatory Bowel Disease
Open this publication in new window or tab >>Epidemiological and therapeutic aspects of Inflammatory Bowel Disease
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
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:nbn:se:oru:diva-65419 (URN)978-91-7529-242-7 (ISBN)
Public defence
2018-05-09, Örebro universitet, Campus USÖ, hörsal C2, Södra Grev Rosengatan 32, Örebro, 09:15 (Swedish)
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Available from: 2018-03-02 Created: 2018-03-02 Last updated: 2018-08-07Bibliographically approved

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Eriksson, CarlRundquist, SaraCao, YangMontgomery, ScottHalfvarson, Jonas

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