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Stopping 5-aminosalicylates in patients with ulcerative colitis starting biologic therapy does not increase the risk of adverse clinical outcomes: analysis of two nationwide population-based cohorts
  1. Ryan C Ungaro1,
  2. Berkeley N Limketkai2,
  3. Camilla Bjørn Jensen3,
  4. Kristine Højgaard Allin3,
  5. Manasi Agrawal4,
  6. Thomas Ullman4,
  7. Jean-Frederic Colombel1,
  8. Tine Jess3
  1. 1 Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
  2. 2 Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
  3. 3 Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark
  4. 4 Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA
  1. Correspondence to Dr Ryan C Ungaro, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA; ryan.ungaro{at}


Objective The benefit of continuing 5-aminosalicylate (5-ASA) in patients with ulcerative colitis (UC) who initiate anti-tumour necrosis factor-alpha (anti-TNF) biologics is unknown. We aimed to compare clinical outcomes in patients with UC already on 5-ASA who started anti-TNF and then either stopped or continued 5-ASA.

Design Our primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, UC-related hospitalisation or surgery. We used two national databases: the United States (US) Truven MarketScan health claims database and the Danish health registers. Patients with UC who started anti-TNF after having been on oral 5-ASA for at least 90 days were included. Patients were classified as stopping 5-ASA if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors and healthcare utilisation. Adjusted HRs (aHR) with 95% CI are reported comparing stopping 5-ASA with continuing 5-ASA.

Results A total of 3589 patients with UC were included (2890 US and 699 Denmark). Stopping 5-ASA after initiating anti-TNF was not associated with an increased risk of adverse clinical events in the U.S. cohort (aHR 1.04; 95% CI 0.90 to 1.21, p=0.57) nor in the Danish cohort (aHR 1.09; 95% CI 0.80 to 1.49, p=0.60). Results were similar in sensitivity analyses investigating concomitant immunomodulator use and duration of 5-ASA treatment before initiating anti-TNF.

Conclusion In two national databases, stopping 5-ASA in patients with UC starting anti-TNF therapy did not increase the risk of adverse clinical events. These results should be validated in a prospective clinical trial.

  • ulcerative colitis
  • biologic
  • mesalamine
  • 5-aminosalicylates

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  • J-FC and TJ contributed equally.

  • RCU and BNL contributed equally.

  • Contributors RCU, TU and JFC developed the study concept. RCU, BNL, CBJ, JFC, KHA and TJ designed the study. BNL and CBJ performed data analysis. RCU, BNL, CBJ, MA, TU, JFC, KHA and TJ interpreted the analyses and contributed substantially to the manuscript. RCU and BNL drafted the first version of the manuscript.

  • Funding Access to the Truven Health MarketScan Commercial Database was provided by the Stanford Center for Population Health Sciences (PHS) Data Core. The PHS Data Core is supported by a National Institutes of Health (NIH) National Center for Advancing Translational Science Clinical and Translational Science Award (UL1 TR001085) and internal Stanford funding. RCU is supported by a Career Development Award from the Crohn’s and Colitis Foundation. This work was supported in part by the Sinai Ulcerative Colitis Clinical, Experimental and System Studies (SUCCESS, grant GCO 14-0560).

  • Competing interests RCU has served as an advisory board member or consultant for Janssen, Pfizer and Takeda; research grant from AbbVie. JFC has served as an advisory board member or consultant for AbbVie, Amgen, Boehringer-Ingelheim, Arena Pharmaceuticals, Celgene, Celltrion, Enterome, Eli Lilly, Ferring Pharmaceuticals, Genentech, Janssen and Janssen, Medimmune, Merck & Co, Nextbiotix, Novartis Pharmaceuticals, Otsuka Pharmaceutical Development & Commercialization, Pfizer, Protagonist, Second Genome, Gilead, Seres Therapeutics, Shire, Takeda, Theradiag; speaker for AbbVie, Ferring, Takeda, Celgene; stock options: Intestinal Biotech Development, Genefit; research grants: AbbVie, Takeda, Janssen and Janssen.

  • Patient consent Not required.

  • Ethics approval The Institutional Review Board of Stanford University.

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

  • Data sharing statement Aggregate data can be requested directly from the authors.