Original Contribution | Published:

Inflammatory Bowel Disease

Long-Term Efficacy and Safety of Cyclosporine in a Cohort of Steroid-Refractory Acute Severe Ulcerative Colitis Patients from the ENEIDA Registry (1989–2013): A Nationwide Multicenter Study

The American Journal of Gastroenterology volume 112, pages 17091718 (2017) | Download Citation

Abstract

Objectives:

To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events.

Methods:

Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators.

Results:

Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed.

Conclusions:

Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.

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Acknowledgements

We are grateful to Ferring Pharmaceuticals for kindly sponsoring the development and maintenance of the ENEIDA project. The funding sources had no involvement in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.

PATIENT CONSENT

Consent was obtained from the patients for this study.

ETHICS APPROVAL

Approval was provided by the committee of each participating center.

Author information

Affiliations

  1. Gastroenterology Department, Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain

    • I Ordás
    •  & J Panés
  2. Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, CIBEREHD, Barcelona, Spain

    • E Domènech
    •  & M Mañosa
  3. Hospital Reina Sofía, IMIBIC, Cordoba’s Univeristy, Cordoba, Spain

    • V García-Sánchez
    •  & E Iglesias-Flores
  4. Gastroenterology Department, Hospital Universitario de Bellvitge, Barcelona, Spain

    • M Peñalva
  5. Gastroenterology Department, Parc Salut Mar, Barcelona, Spain

    • A Cañas-Ventura
  6. Gastroenterology Department, Hospital de Cruces, Bilbao, Spain

    • O Merino
  7. Department of Gastroenterology, Hospital Universitari Mútua Terrassa, University of Barcelona, CIBERHD, Barcelona, Spain

    • F Fernández-Bañares
    •  & M Esteve
  8. Gastroenterology Department, Hospital Lozano Blesa, CIBEREHD, Zaragoza, Spain

    • F Gomollón
  9. Gastroenterology Department, Hospital Puerta de Hierro Majadahonda, Madrid, Spain

    • M Vera
  10. Gastroenterology Department, Hospital Universitario de Alicante, Alicante, Spain

    • A Gutiérrez
  11. Gastroenterology Department, Hospital de Sant Pau, Barcelona, Spain

    • E Garcia-Planella
  12. Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), CIBEREHD, Madrid, Spain

    • M Chaparro
  13. Gastroenterology Department, Hospital la Fe, CIBEREHD, Valencia, Spain

    • M Aguas
  14. Gastroenterology Department, Hospital General Yagìe, Burgos, Spain

    • E Gento
  15. Gastroenterology Department, Complejo Asistencial Universitario de León, Leon, Spain

    • F Muñoz
  16. Gastroenterology Department, Hospital de Galdakao, Bilbao, Spain

    • M Aguirresarobe
  17. Gastroenterology Department, Hospital de Basurto, Bilbao, Spain

    • C Muñoz
  18. Gastroenterology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain

    • L Fernández
  19. Gastroenterology Department, Corporació Sanitària Universitària Parc Taulí, CIBEREHD, Barcelona, Spain

    • X Calvet
  20. Gastroenterology Department, Complejo Hospitalario de Navarra, Navarra, Spain

    • C E Jiménez
  21. Gastroenterology Department, Hospital San Jorge, Huesca, Spain

    • M A Montoro
  22. Gastroenterology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain

    • A Mir
  23. Gastroenterology Department, Complexo Hospitalario Universitario de Vigo-Instituto de Investigación Biomédica, Pontevedra, Spain

    • M L De Castro
  24. Gastroenterology Department, Hospital de Elche, Alicante, Spain

    • M F García-Sepulcre
  25. Gastroenterology Department, Hospital de Fuenlabrada, Madrid, Spain

    • F Bermejo

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Competing interests

Guarantor of the article: Ingrid Ordas, MD, PhD.

Specific author contributions: Design of the study, study coordination, acquisition of data, statistical analysis and interpretation of data, manuscript writing, critical revision of the manuscript, and approval of the final draft submitted: I.O., M.E.; acquisition of data, critical revision of the manuscript, and approval of the final draft submitted: E.D., F.F.-B., M.C., X.C., M.L.C., F.M., F.G., and J.P.; acquisition of data, approval of the final draft submitted: V.G.-S., M.P., A.C.-V., O.M., M.V., A.G., E.G.-P., M.A., E.G., M.A., C.M., L.F., C.E.J., M.A.M., A.M., M.F.G.-S., and F.B.

Financial support: None.

Potential competing interests: None.

Corresponding author

Correspondence to M Esteve.

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DOI

https://doi.org/10.1038/ajg.2017.180

SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/ajg

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