Digestive Diseases and Sciences

, Volume 63, Issue 10, pp 2555–2563 | Cite as

Physicians’ Perspectives on Cost, Safety, and Perceived Efficacy Determine Aminosalicylate Use in Crohn’s Disease

  • Christopher Ma
  • Carla Ascoytia
  • Kelly P. McCarrier
  • Mona Martin
  • Brian G. Feagan
  • Vipul Jairath
Original Article



Aminosalicylates are the most commonly prescribed therapy in Crohn’s disease (CD), despite uncertainty in the evidence to support their efficacy.


To examine physicians’ perspectives on aminosalicylate use for CD and explore the discordance between clinical practice and the evidence base.


A qualitative interview study was performed amongst physicians with at least 4 years of independent experience in managing CD patients. Semi-structured telephone interviews were conducted using an exploratory interview guide. Interview transcripts were thematically analyzed to elucidate concepts pertaining to treatment strategies for CD, motivations for prescribing aminosalicylates, perceived benefits and harms of aminosalicylate use, and the relationship between the evidence and real-world prescribing practices.


A representative sample of thirty physicians from four different countries and multiple practice environments (university/teaching hospitals, public practice, private/community practice, and subspecialty gastroenterology clinics) participated. Nearly all physicians (93.3%, 28/30) reported prescribing aminosalicylates for CD. Aminosalicylates were endorsed as first-line therapy for mild CD by nearly half of participants (13/30, 43.3%). A favorable safety profile, possible efficacy in mild colonic CD, and patient reluctance to step-up to other therapies were primary motivators for aminosalicylate use. Almost half of respondents (46.7%) expressed that the evidence informing aminosalicylate efficacy in CD differed substantially from their own clinical experience.


Physicians’ beliefs about efficacy in subgroups of CD patients, safety, and patient preferences primarily motivate aminosalicylate prescription in CD. There is a lack of confidence in published clinical trials, and a desire for more robust evidence to inform 5-ASA use in CD.


Crohn’s disease Aminosalicylates Mesalamine Sulfasalazine 



This research was conducted in a collaboration between Health Research Associates, Inc. and Robarts Clinical Trials, Inc.

Author’s contribution

CM was involved in data analysis, manuscript drafting, and editing. CA and MM performed data acquisition and analysis and manuscript editing. KPM contributed to study design, data acquisition and analysis, and manuscript editing. BGF was involved in study concept and design, data analysis, and manuscript editing. VJ performed study concept and design, data analysis, manuscript drafting and editing, study supervision. VJ is acting as the article guarantor.


This work was not specifically supported by any funding agency in the public, commercial, or not-for-profit sectors. Christopher Ma is supported by a Clinician Fellowship from the Canadian Institutes of Health Research and the Canadian Association of Gastroenterology. Vipul Jairath receives salary support from the John and Susan McDonald Endowed Chair at Western University, London, Ontario, Canada

Compliance with ethical standards

Conflict of interest

Christopher Ma has no conflicts of interest to declare. Carla Ascoytia, Kelly McCarrier, and Mona Martin are employed by Health Research Associates (HRA). HRA received funding to conduct the interviews and analyze the qualitative data but the authors have no additional individual conflicts of interest to declare. Brian Feagan has received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor Inc., Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix, and Wyeth Pharmaceuticals Inc.; consulting fees from Millennium Pharmaceuticals, Merck, Centocor Inc., Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie, Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging Inc., Salix Pharmaceuticals, Novo Nordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc., and Sigmoid Pharma; and speaker’s fees from UCB, AbbVie, and J&J/Janssen. Vipul Jairath has received consulting fees from AbbVie, Sandoz, Takeda, Janssen, Robarts Clinical Trials; speaker’s fees from Takeda, Janssen, Shire, Ferring.

Supplementary material

10620_2018_5181_MOESM1_ESM.pdf (296 kb)
Supplemental Appendix 1 Complete Interview Guide (PDF 295 kb)


  1. 1.
    Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110:1324–1338.CrossRefPubMedGoogle Scholar
  2. 2.
    Duijvestein M, Battat R, Vande Casteele N, D’Haens GR, et al. Novel therapies and treatment strategies for patients with Inflammatory bowel disease. Curr Treat Options Gastroenterol. 2018;16:129–146.CrossRefPubMedGoogle Scholar
  3. 3.
    Schnitzler F, Fidder H, Ferrante M, Noman M, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm Bowel Dis. 2009;15:1295–1301.CrossRefPubMedGoogle Scholar
  4. 4.
    Baert F, Moortgat L, Van Assche G, Caenepeel P, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138:463–468.CrossRefPubMedGoogle Scholar
  5. 5.
    Rogler G. Top-down or step-up treatment in Crohn’s disease? Dig Dis. 2013;31:83–90.CrossRefPubMedGoogle Scholar
  6. 6.
    Khanna R, Bressler B, Levesque BG, Zou G, et al. Early combined immunosuppression for the management of Crohn’s disease (REACT): a cluster randomised controlled trial. Lancet. 2015;386:1825–1834.CrossRefPubMedGoogle Scholar
  7. 7.
    D’Haens G, Baert F, van Assche G, Caenepeel P, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet. 2008;371:660–667.CrossRefPubMedGoogle Scholar
  8. 8.
    Bernstein CN, Nugent Z, Blanchard JF. 5-aminosalicylate is not chemoprophylactic for colorectal cancer in IBD: a population based study. Am J Gastroenterol. 2011;106:731–736.CrossRefPubMedGoogle Scholar
  9. 9.
    Schoepfer AM, Bortolotti M, Pittet V, Mottet C, et al. The gap between scientific evidence and clinical practice: 5-aminosalicylates are frequently used for the treatment of Crohn’s disease. Aliment Pharmacol Ther. 2014;40:930–937.CrossRefPubMedGoogle Scholar
  10. 10.
    Benchimol EI, Cook SF, Erichsen R, Long MD, et al. International variation in medication prescription rates among elderly patients with inflammatory bowel disease. J Crohns Colitis. 2013;7:878–889.CrossRefPubMedGoogle Scholar
  11. 11.
    Holko P, Kawalec P, Stawowczyk E. Prevalence and drug treatment practices of inflammatory bowel diseases in Poland in the years 2012–2014: an analysis of nationwide databases. Eur J Gastroenterol Hepatol. 2017;30:456–464.Google Scholar
  12. 12.
    Paridaens K, Yip YL, Ghatnekar O, Plassais M, et al. Real-world evidence (RWE) on outcomes and clinical treatment patterns of 5-aminosalicylic acid (5-ASA) in mild Crohn’s disease (CD) from European healthcare databases (the CROHN’S investigation). J Crohns Colitis. 2018;12:P485.CrossRefGoogle Scholar
  13. 13.
    Akobeng AK, Zhang D, Gordon M, MacDonald JK. Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn’s disease. Cochrane Database Syst Rev. 2016;9:CD003715.PubMedGoogle Scholar
  14. 14.
    Lim WC, Wang Y, MacDonald JK, Hanauer S. Aminosalicylates for induction of remission or response in Crohn’s disease. Syst Rev. 2016;7:CD00887.Google Scholar
  15. 15.
    Danese S, Fiorino G, Fernandes C, Peyrin-Biroulet L. Catching the therapeutic window of opportunity in early Crohn’s disease. Curr Drug Targets. 2014;15:1056–1063.CrossRefPubMedGoogle Scholar
  16. 16.
    Ransford RA, Langman MJ. Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines. Gut. 2002;51:536–539.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. Int J Qual Health Care. 2007;19:349–357.CrossRefPubMedGoogle Scholar
  18. 18.
    Summers RW, Switz DM, Sessions JT Jr, Becktel JM, et al. National Cooperative Crohn’s Disease Study: results of drug treatment. Gastroenterology. 1979;77:847–869.PubMedGoogle Scholar
  19. 19.
    Malchow H, Ewe K, Brandes JW, Goebell H, et al. European Cooperative Crohn’s Disease Study (ECCDS): results of drug treatment. Gastroenterology. 1984;86:249–266.PubMedGoogle Scholar
  20. 20.
    Singleton JW, Hanauer SB, Gitnick GL, Peppercorn MA, et al. Mesalamine capsules for the treatment of active Crohn’s disease: results of a 16-week trial. Pentasa Crohn’s Disease Study Group. Gastroenterology. 1993;104:1293–1301.CrossRefPubMedGoogle Scholar
  21. 21.
    Gomollon F, Dignass A, Annese V, Tilg H, et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J Crohns Colitis. 2017;11:3–25.CrossRefPubMedGoogle Scholar
  22. 22.
    Hart AL, Lomer M, Verjee A, Kemp K, et al. What Are the top 10 research questions in the treatment of inflammatory bowel disease? A priority setting partnership with the James Lind Alliance. J Crohns Colitis. 2017;11:204–211.CrossRefPubMedGoogle Scholar
  23. 23.
    Lichtenstein GR, Hanauer SB, Sandborn WJ. Practice Parameters Committee of American College of G. Management of Crohn’s disease in adults. Am J Gastroenterol. 2009;104:465–483.CrossRefPubMedGoogle Scholar
  24. 24.
    Sandborn WJ. Crohn’s disease evaluation and treatment: clinical decision tool Gastroenterology. 2014;147:702–705.PubMedGoogle Scholar
  25. 25.
    Tremaine WJ, Schroeder KW, Harrison JM, Zinsmeister AR. A randomized, double-blind, placebo-controlled trial of the oral mesalamine (5-ASA) preparation, Asacol, in the treatment of symptomatic Crohn’s colitis and ileocolitis. J Clin Gastroenterol. 1994;19:278–282.CrossRefPubMedGoogle Scholar
  26. 26.
    Hanauer SB, Stromberg U. Oral Pentasa in the treatment of active Crohn’s disease: a meta-analysis of double-blind, placebo-controlled trials. Clin Gastroenterol Hepatol. 2004;2:379–388.CrossRefPubMedGoogle Scholar
  27. 27.
    Feagan BG. 5-ASA therapy for active Crohn’s disease: old friends, old data, and a new conclusion. Clin Gastroenterol Hepatol. 2004;2:376–378.CrossRefPubMedGoogle Scholar
  28. 28.
    Jairath V, Hokkanen S, Guizzetti L, Boxall N, Campbell-Hill S, Patel H. 5-ASA prescription trends over time in inflammatory bowel disease 1996 to 2015: a UK population-based study. J Crohns Colitis. 2018;12:405.CrossRefGoogle Scholar
  29. 29.
    Silverstein MD, Loftus EV, Sandborn WJ, Tremaine WJ, et al. Clinical course and costs of care for Crohn’s disease: Markov model analysis of a population-based cohort. Gastroenterology. 1999;117:49–57.CrossRefPubMedGoogle Scholar
  30. 30.
    Peluso R, Manguso F, Vitiello M, Iervolino S, Di Minno MN. Management of arthropathy in inflammatory bowel diseases. Ther Adv Chronic Dis. 2015;6:65–77.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    van Staa TP, Card T, Logan RF, Leufkens HG. 5-Aminosalicylate use and colorectal cancer risk in inflammatory bowel disease: a large epidemiological study. Gut. 2005;54:1573–1578.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Cockburn J, Pit S. Prescribing behaviour in clinical practice: patients’ expectations and doctors’ perceptions of patients’ expectations: a questionnaire study. BMJ. 1997;315:520–523.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Lado E, Vacariza M, Fernandez-Gonzalez C, Gestal-Otero JJ, Figueiras A. Influence exerted on drug prescribing by patients’ attitudes and expectations and by doctors’ perception of such expectations: a cohort and nested case-control study. J Eval Clin Pract. 2008;14:453–459.CrossRefPubMedGoogle Scholar
  34. 34.
    Siegel CA, Horton H, Siegel LS, Thompson KD, et al. A validated web-based tool to display individualised Crohn’s disease predicted outcomes based on clinical, serologic and genetic variables. Aliment Pharmacol Ther. 2016;43:262–271.CrossRefPubMedGoogle Scholar
  35. 35.
    Kim KJ, Kwak MS, Soh JS, Cho DH, et al. Adding 5-aminosalicylate to immunomodulators showed no additional benefit in Crohn’s disease. J Crohns Colitis. 2018;12:P493.CrossRefGoogle Scholar
  36. 36.
    Limketkai B, Ungaro R, Jess T, Allin K, et al. Discontinuation of 5-aminosalicylates after starting biologic therapy in patients with ulcerative colitis is not associated with adverse outcomes. J Crohns Colitis. 2018;12:P363.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Christopher Ma
    • 1
    • 2
  • Carla Ascoytia
    • 3
  • Kelly P. McCarrier
    • 3
  • Mona Martin
    • 3
  • Brian G. Feagan
    • 2
    • 4
    • 5
  • Vipul Jairath
    • 2
    • 4
    • 5
  1. 1.Division of Gastroenterology and HepatologyUniversity of CalgaryCalgaryCanada
  2. 2.Robarts Clinical Trials, Inc.LondonCanada
  3. 3.Health Research Associates, Inc.Mountlake TerraceUSA
  4. 4.Department of MedicineWestern UniversityLondonCanada
  5. 5.Department of Biostatistics and EpidemiologyWestern UniversityLondonCanada

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