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  • Perspective
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Head-to-head trials in inflammatory bowel disease: past, present and future

Nature Reviews Gastroenterology & Hepatology volume 17, pages 365–376 (2020)Cite this article

An Author Correction to this article was published on 05 January 2021

This article has been updated

Abstract

With the increase in the number of novel drugs for inflammatory bowel disease (IBD), comparing therapeutic options or strategies has become a key challenge in IBD trials. Head-to-head trials designed and powered to enable formal comparisons are the gold standard in comparative research. Indeed, these trials are requested by some health authorities for evaluating the positioning of new treatments in IBD, as well as helping prescribing physicians to select the most appropriate treatment options for their patients. Despite head-to-head trials including aminosalicylate therapy in IBD having been performed decades ago, the first results of a randomized controlled trial directly comparing biologic agents with different modes of action have only now been published, mainly owing to important methodological issues. This Perspective provides an overview of the past, current and future concepts in IBD trial design, with a detailed focus on the role of comparative research and the challenges and pitfalls in undertaking and interpreting the results from such studies.

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Fig. 1: Key events in IBD drug development.
Fig. 2: Randomized controlled trials versus observational studies.
Fig. 3: Types of head-to-head trial and their advantages and disadvantages.
Fig. 4: Ongoing head-to-head trials in IBD.

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Change history

  • 05 January 2021

    A Correction to this paper has been published: https://doi.org/10.1038/s41575-020-00409-x.

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Authors and Affiliations

  1. Imelda GI Clinical Research Centre, Imeldaziekenhuis Bonheiden, Bonheiden, Belgium

    Lieven Pouillon & Peter Bossuyt

  2. Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

    Simon Travis

  3. IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center – IRCCS –, Rozzano, Milan, Italy

    Silvio Danese

  4. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy

    Silvio Danese

  5. Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France

    Laurent Peyrin-Biroulet

  6. Inserm U1256 NGERE, Lorraine University, Vandoeuvre-lès-Nancy, France

    Laurent Peyrin-Biroulet

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L.P., S.T. and L.P.-B. researched data for and wrote the article. All authors made substantial contributions to discussion of content and reviewed/edited the manuscript before submission.

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Correspondence to Laurent Peyrin-Biroulet.

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Competing interests

L.P. received personal fees from Abbvie, Ferring, Takeda; and advisory board fees from Takeda. S.T. received research support from AbbVie, Buhlmann, Celgene, International Organization for the Study of Inflammatory Bowel Disease, Janssen, Lilly, Takeda, UCB, Vifor and Norman Collisson Foundation; consulting fees from AbbVie, Allergan, Amgen, Arena, Asahi, Astellas, Biocare, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Buhlmann, Celgene, Chemocentryx, Cosmo, Enterome, Ferring, Giuliani SpA, GSK, Genentech, Gilead, Immunocore, Immunometabolism, Indigo, Janssen, Lexicon, Lilly, Merck, MSD, Neovacs, Novartis, NovoNordisk, NPS Pharmaceuticals, Pfizer, Proximagen, Receptos, Roche, Sandoz, Sensyne, Shire, Sigmoid Pharma, SynDermix, Takeda, Theravance, Tillotts, Topivert, UCB, VHsquared, Vifor and Zeria; speaker fees from AbbVie, Amgen, Biogen, Ferring, Janssen, Shire and Takeda; and declares no stock or share options. P.B. received educational grants from AbbVie, Mundipharma, Pfizer and Janssen; speaker fees from AbbVie, Takeda and Pfizer; and advisory board fees from Hospira, Janssen, MSD, Mundipharma, Roche, Pfizer, Takeda, Sandoz and Pentax. S.D. has served as a speaker, a consultant and an advisory board member for Abbvie, Ferring, Hospira, Johnson & Johnson, Merck, Millennium Takeda, Mundipharma, Pfizer, Tigenix, UCB Pharma and Vifor. L.P.-B. received personal fees from AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boerhinger Ingelheim, Pfizer, Index Pharmaceuticals Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera and Theravance; grants from Abbvie, MSD and Takeda; and stock options from CTMA.

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Pouillon, L., Travis, S., Bossuyt, P. et al. Head-to-head trials in inflammatory bowel disease: past, present and future. Nat Rev Gastroenterol Hepatol 17, 365–376 (2020). https://doi.org/10.1038/s41575-020-0293-9

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