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Spondyloarthritis with inflammatory bowel disease: the latest on biologic and targeted therapies

Nature Reviews Rheumatology volume 19, pages 503–518 (2023)Cite this article

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Abstract

Spondyloarthritis (SpA) encompasses a heterogeneous group of chronic inflammatory diseases that can affect both axial and peripheral joints, tendons and entheses. Among the extra-articular manifestations, inflammatory bowel disease (IBD) is associated with considerable morbidity and effects on quality of life. In everyday clinical practice, treatment of these conditions requires a close collaboration between gastroenterologists and rheumatologists to enable early detection of joint and intestinal manifestations during follow-up and to choose the most effective therapeutic regimen, implementing precision medicine for each patient’s subtype of SpA and IBD. The biggest issue in this field is the dearth of drugs that are approved for both diseases, as only TNF inhibitors are currently approved for the treatment of full-spectrum SpA–IBD. Janus tyrosine kinase inhibitors are among the most promising drugs for the treatment of peripheral and axial SpA, as well as for intestinal manifestations. Other therapies such as inhibitors of IL-23 and IL-17, phosphodiesterase 4 inhibitor, α4β7 integrin blockers and faecal microbiota transplantation seem to only be able to control some disease domains, or require further studies. Given the growing interest in the development of novel drugs to treat both conditions, it is important to understand the current state of the art and the unmet needs in the management of SpA–IBD.

Key points

  • Cytokine dysregulation is a main underlying factor involved in the pathogenesis of spondyloarthritis (SpA) and inflammatory bowel disease (IBD).

  • The co-occurrence of SpA and IBD requires a multidisciplinary approach, in which rheumatologists and gastroenterologists must work together to achieve the accurate diagnosis and the most effective drug choice.

  • Limited treatment options are currently available for combined SpA and IBD, and a failure of treatment response to anti-TNF, especially in patients with axial SpA and IBD, poses a particular challenge for clinicians.

  • Inhibitors of Janus kinases are among the most promising drugs for the treatment of full-spectrum SpA–IBD.

  • Further studies are needed to better understand the potential of several therapies, to enable the implementation of precision medicine and to find a balance between safety and efficacy.

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Fig. 1: IL-23 and IL-17 pathways and therapeutic targets in spondyloarthritis and inflammatory bowel disease.
Fig. 2: Stages of development and targets of drugs in spondyloarthritis and inflammatory bowel disease.

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Acknowledgements

The authors would like to thank Augusta Ortolan for comments that greatly improved the manuscript, and Eric Franck Nde for editing the English version.

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Authors and Affiliations

  1. Rheumatology Unit, Department of Medicine-DIMED, Padova University Hospital, Padova, Italy

    Giacomo Cozzi, Laura Scagnellato, Mariagrazia Lorenzin, Francesca Ometto, Marta Favero, Andrea Doria & Roberta Ramonda

  2. Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, Padova, Italy

    Edoardo Savarino & Fabiana Zingone

  3. Department of Gastroenterology and Hepatology, University Hospital Zürich and Center for Gastroenterology and Hepatology, Zürich, Switzerland

    Stephan R. Vavricka

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Contributions

G.C. and L.S. researched data for the article and wrote the article. R.R., G.C., M.L. and A.D. contributed substantially to discussion of the content. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to Roberta Ramonda.

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Competing interests

G.C., L.S., F.O. and M.F. declare no competing interests; M.L. has received consulting fees from AbbVie; E.S. has served as a speaker for AbbVie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots and Unifarco, as a consultant for AbbVie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Takeda and Unifarco, and has received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco and Zeta Farmaceutici; F.Z. has served as speaker for EG Stada Group, Fresenius Kabi, Janssen, Pfizer, Takeda, Unifarco and Malesci, and has served as a consultant for Galapagos; A.D. has received consulting fees from GSK, Pfizer, AstraZeneca, Celgene, Eli Lilly and Baxalta; S.R.V. has received consulting fees, speaker’s honoraria and unrestricted research grants from Abbott, Alfasigma, Amgen, Arenapharm, BMS, Falk Pharma GmbH, Ferring Pharmaceuticals, Gilead, iQuone, Janssen, MSD, Permamed, Pfizer, Sanofi-Aventis, Schwabe Pharma, Takeda, Tillotts, UCB and Vifor; R.R. has received honoraria and speaker fees from Novartis, AbbVie, Pfizer, MSD and Janssen.

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Cozzi, G., Scagnellato, L., Lorenzin, M. et al. Spondyloarthritis with inflammatory bowel disease: the latest on biologic and targeted therapies. Nat Rev Rheumatol 19, 503–518 (2023). https://doi.org/10.1038/s41584-023-00984-8

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