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Clinical Drug Investigation

, Volume 39, Issue 8, pp 799–803 | Cite as

Inflammatory Bowel Disease Onset During Secukinumab Treatment: Real Concern or Just an Expression of Dysregulated Immune Response?

  • Walter FriesEmail author
  • Alessandra Belvedere
  • Maria Cappello
  • Ambrogio Orlando
  • Gianluca Trifirò
Short Communication

Abstract

Background

Up to December 2018, eight cases of new-onset inflammatory bowel disease (IBD) were reported in the literature in patients being treated with secukinumab, an interleukin-17A antagonist prescribed for dermatologic or rheumatologic indications. The duration of secukinumab treatment ranged from a single administration to 12 months of treatment.

Objective

The aim of our investigation was to estimate the cumulative incidence of new-onset IBD in patients treated with secukinumab for either dermatologic or rheumatologic indications.

Methods

We carried out a survey among the dermatology and rheumatology centres in the Sicilian region (Italy) in order to identify the number of patients treated with secukinumab in the previous 24 months (November 2016–November 2018), and to understand how many of these patients eventually developed IBD after the start of secukinumab therapy.

Results

Overall, four cases of IBD during secukinumab treatment were identified, with higher variability in time to onset compared with what has been previously reported, i.e. from 1 month to 5 years of secukinumab exposure. Overall, 434 patients were treated with secukinumab in Sicily between November 2016 and November 2018, and approximately 1% of these patients developed new-onset IBD.

Conclusions

Careful clinical examination of patients with respect to possible susceptibility to IBD prior to secukinumab therapy is advised.

Notes

Acknowledgements

The authors wish to thank the following members of the SN-IBD, and colleagues from the Dermatology and Rheumatology Units (in alphabetical order): Fabiola Atzeni, MD, Rheumatology, Policlinico ‘G. Martino’, University of Messina, Messina; Carmelo Bertolami, MD, Gastroenterology Unit, A.O.O.R. ‘Papardo Piemonte’, Messina; Maria Rita Bongirono, MD, Institute of Dermatology, University of Palermo, Palermo; Antonio Carroccio, MD, Internal Medicine Unit, A.O. ‘Giovanni Paolo II’, Sciacca; Serafinella Cannavò, Dermatology, Policlinico ‘G. Martino’, University of Messina, Messina; Aldo Mollica-Colella, MD, Rheumatology Unit, A.O.O.R. ‘Papardo Piemonte’, Messina; Roberto di Mitri, MD, Gastroenterology and Endoscopy Unit, A.R.N.A.S. ‘Civico Di Cristina Benfratelli’, Palermo; Serena Garufi, MD, Gastroenterology Unit, A.O.S. Elia, P.O. Raimondi, Caltanisetta (CL); Claudio Guarneri, MD, Dermatology, Policlinico ‘G. Martino’, University of Messina, Messina; Gaetano Inserra, MD, Gastroenterology Unit, A.O.U. Policlinico – “Vittorio Emanuele”, Catania; Michele Lo Re, Dermatology, A.O.O.R. ‘Papardo Piemonte’, Messina; Antonio Magnano, Gastroenterology Unit, A.O.U. Policlinico – “Vittorio Emanuele”, Catania; Giovanni Magrì, MD, Gastroenterology Unit, A.O. ‘Santa Marta e S. Venera’, Acireale (CT); Salvatore Pellegrino, Paediatric Gastroenterology, Policlinico ‘G. Martino’, University of Messina, Messina; Sara Renna, MD, IBD-Unit, “Villa Sofia-Cervello Hospital, Palermo; Barbara Scrivo, MD, Gastroenterology and Hepatology Unit, A.O.U. Policlinico “P. Giaccone”, Palermo; Antonino Trovatello: Surgery Unit, A.O. ‘Umberto I’, Syracuse; Roberto Vasallo, MD, Gastroenterology and Endoscopy Unit, A.O. ‘Buccheri La Ferla Fatebenefratelli’, Palermo, Italy.

Compliance with Ethical Standards

Funding

No funding was received to conduct this study.

Conflicts of Interest

Walter Fries, Alessandra Belvedere, Maria Cappello, Ambrogio Orlando and Gianluca Trifirò have no conflicts of interest to declare.

Ethics Approval

The protocol was approved by the local Ethics Committee of the coordinating centre (Messina; protocol n. 45/19). Written consent was not required.

References

  1. 1.
    Gazzetta Ufficiale della Repubblica Italiana. Scheda prescrizione cartacea dei farmaci biologici per la psoriasi a placche. 2016. http://www.gazzettaufficiale.it/do/atto/serie_generale/caricaPdf?cdimg=16A0791300100010110001&dgu=2016-11-11&art.dataPubblicazioneGazzetta=2016-11-11&art.codiceRedazionale=16A07913&art.num=1&art.tiposerie=SG. Accessed 14 Jan 2019.
  2. 2.
    Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, Mckenzie B, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006;116:1310–6.CrossRefGoogle Scholar
  3. 3.
    Hohenberger M, Cardwell LA, Oussedik E, Feldman SR. Interleukin-17 inhibition: role in psoriasis and inflammatory bowel disease. J Dermatolog Treat. 2018;29:13–8.CrossRefGoogle Scholar
  4. 4.
    Hueber W, Sands BE, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins PD, Secukinumab in Crohn’s Disease Study Group, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61:1693–700.CrossRefGoogle Scholar
  5. 5.
    Targan SR, Feagan B, Vermeire S, Panaccione R, Melmed GY, Landers C, et al. A randomized, double-blind, placebo-controlled phase 2 study of brodalumab in patients with moderate-to-severe Crohn’s disease. Am J Gastroenterol. 2016;111:1599–607.CrossRefGoogle Scholar
  6. 6.
    Lee JS, Tato CM, Joyce-Shaikh B, Gulan F, Cayatte C, Chen Y, et al. Interleukin-23-Independent IL-17 production regulates intestinal epithelial permeability. Immunity. 2015;43:727–38.CrossRefGoogle Scholar
  7. 7.
    Ehrlich D, Jamaluddin N, Pisegna J, Padua D. A challenging case of severe ulcerative colitis following the initiation of secukinumab for ankylosing spondylitis. Case Rep Gastrointest Med. 2018;2018:9679287.Google Scholar
  8. 8.
    Fobelo Lozano MJ, Serrano Giménez R, Castro Fernández M. Emergence of Inflammatory Bowel Disease During Treatment With Secukinumab. J Crohn’s Colitis. Epub 9 May 2018.  https://doi.org/10.1093/ecco-jcc/jjy063.
  9. 9.
    Wang J, Bhatia A, Cleveland NK, Gupta N, Dalal S, Rubin DT, et al. Rapid onset of inflammatory bowel disease after receiving Secukinumab Infusion. ACG Case Rep J. 2018;5:e56.CrossRefGoogle Scholar
  10. 10.
    Vernero M, Astegiano M, Ribaldone DG. New onset of inflammatory bowel disease in three patients undergoing IL-17A inhibitor secukinumab: a case series. Am J Gastroenterol. 2019;114:179–80.CrossRefGoogle Scholar
  11. 11.
    Uchida S, Oiso N, Komeda Y, Kudo M, Kawada A. Paradoxical ulcerative colitis during treatment with secukinumab for psoriasis. Eur J Dermatol. Epub 13 Nov 2018.  https://doi.org/10.1684/ejd.2018.3391.
  12. 12.
    Orrell KA, Murphrey M, Kelm RC, Lee HH, Pease DR, Laumann AE, et al. Inflammatory bowel disease events after exposure to interleukin 17 inhibitors secukinumab and ixekizumab: postmarketing analysis from the RADAR (“Research on Adverse Drug events And Reports”) program. J Am Acad Dermatol. 2018;79(4):777–8.CrossRefGoogle Scholar
  13. 13.
    Macaluso FS, Fries W, Privitera AC, Cappello M, Siringo S, Inserra G, et al. A Propensity Score-matched Comparison of Infliximab and Adalimumab in Tumour Necrosis Factor-α Inhibitor-naïve and Non-naïve Patients With Crohn’s Disease: Real-Life Data From the Sicilian Network for Inflammatory Bowel Disease. J Crohn’s Colitis. 2019;13:209–17.CrossRefGoogle Scholar
  14. 14.
    Mease PJ, Kavanaugh A, Reimold A, Tahir H, Rech J, Hall S, et al. Secukinumab in the treatment of psoriatic arthritis: efficacy and safety results through 3 years from the year 1 extension of the randomised phase III FUTURE 1 trial. RMD Open. 2018;4(2):e000723.CrossRefGoogle Scholar
  15. 15.
    Van De Kerkhof PCM, Griffiths CEM, Reich K, Leonardi CL, Blauvelt A, Tsai TF, et al. Secukinumab long-term safety experience: A pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2016;75(83–98):e4.Google Scholar
  16. 16.
    Braun J, Baraliakos X, Deodhar A, Baeten D, Sieper J, Emery P, et al. Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study. Ann Rheum Dis. 2017;76:1070–7.CrossRefGoogle Scholar
  17. 17.
    Schreiber S, Colombel JF, Feagan BG, Reich K, Deodhar AA, McInnes IB, et al. Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials. Ann Rheum Dis. 2019;78(4):473–9.CrossRefGoogle Scholar
  18. 18.
    Uppsala Monitoring Centre and WHO Collaborating Centre for International Drug Monitoring. VigiAccess™. www.vigiaccess.org. Accessed 14 Jan 2019.
  19. 19.
    Eudravigilance. https://bi.ema.europa.eu/analyticsSOAP/saw.dll?PortalPages. Accessed 14 Jan 2019.
  20. 20.
    Department of Health, Therapeutic Goods Administration, Australian Government. Database of Adverse Event Notifications (DAEN). https://www.tga.gov.au/database-adverse-event-notifications-daen. Accessed 14 Jan 2019.
  21. 21.
    Canada Vigilance Adverse Reaction Online Database. https://cvp-pcv.hc-sc.gc.ca/arq-rei/index-eng.jsp. Accessed 14 Jan 2019.

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.IBD Unit, Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly
  2. 2.Gastroenterology and Hepatology UnitAOU Policlinico “P. Giaccone”PalermoItaly
  3. 3.Division of Internal MedicineVilla Sofia-Cervello HospitalPalermoItaly
  4. 4.Department of Biomedical and Dental Sciences and Morphofunctional ImagingUniversity of MessinaMessinaItaly

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