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Original article
Impact of thiopurines on the natural history and surgical outcome of ulcerative colitis: a cohort study
  1. Carl Eriksson1,
  2. Sara Rundquist1,
  3. Yang Cao2,3,
  4. Scott Montgomery2,4,5,
  5. Jonas Halfvarson1
  1. 1Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
  2. 2Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden
  3. 3Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  4. 4Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
  5. 5Department of Epidemiology and Public Health, University College London, London, UK
  1. Correspondence to Dr Carl Eriksson, Department of Gastroenterology, Faculty of Medicine and HealthÖrebro , University, Örebro SE-70182, Sweden; carl.eriksson{at}regionorebrolan.se

Abstract

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.

  • chronic ulcerative colitis
  • azathioprine
  • 6-mercaptopurine
  • tnf-alpha

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Footnotes

  • Contributors CE, JH and SM planned and conducted the study. CE and SR collected the data. CE and YC performed the data analyses. CE, JH, SM, SR and YC interpreted the data. CE and JH drafted the manuscript. CE, JH, SM and YC revised the manuscript. CE, JH, SM, SR and YC approved the final draft of the manuscript.

  • Funding CE was financially supported by the Swedish government’s agreement on medical training and research (OLL-549221).

  • Competing interests CE: research grant from the Swedish government’s agreement on medical training and research and speaker’s fee from Takeda. JH: research grants from the Swedish Research Council, the Örebro University Hospital Research Foundation, the Swedish Foundation for Strategic Research and speaker’s and/or consultancy fees from Abbvie, Hospira, Janssen, Medivir, MSD, Pfizer, RenapharmaVifor and Takeda.

  • Patient consent Not required.

  • Ethics approval The study was approved by the Uppsala Regional Ethics Committee in 2010 (approval no. 2010/304).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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