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Infliximab Dose Escalation as an Effective Strategy for Managing Secondary Loss of Response in Ulcerative Colitis

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Abstract

Background

The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated.

Aims

To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC.

Methods

This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis.

Results

Seventy-nine patients were included. Fifty-four patients (68.4 %) achieved short-term clinical response and 41 patients (51.9 %) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8–26], 33 patients (41.8 %) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95 % confidence interval (CI) 0.12–0.49; p < 0.001]. During a median follow-up of 24 months (IQR 13–34), 9 patients (11.4 %) needed colectomy. Short-term response was identified as a predictor of colectomy avoidance (HR 0.14; 95 % CI 0.03–0.69; p < 0.007).

Conclusions

In UC patients who lost response to infliximab during maintenance, infliximab dose escalation enabled recovery of short-term response in nearly 70 % of patients. In the long term, 58 % of patients maintained sustained clinical benefit, and 9 of 10 avoided colectomy. Short-term response was associated with an 86 % reduction in the relative risk of colectomy.

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Acknowledgments

The authors would like to thank Dr. C. Fernandez for her assistance in the statistical analysis and Dr. G. Morley for writing support and for reviewing the English manuscript.

Conflict of interest

C.T., M.B., M.C., C.S., G.B., M.D.M., J.P.G., V.G., I.M., F.B., M.Ch., M.P.M., J.L.M., and I.F. have served as a speaker and consultant for MSD and AbbVie. M.Ch. has received research funding from MSD and AbbVie. The remaining authors declare that they have nothing to disclose. Writing support was provided by G. Morley and funded by MSD of Spain.

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Authors and Affiliations

  1. Inflammatory Bowel Disease Unit, Department of Gastroenterology, Hospital Clínico San Carlos, c/Profesor Martín Lagos s/n, 28040, Madrid, Spain

    Carlos Taxonera, David Olivares, Cristina Alba & Juan L. Mendoza

  2. Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain

    Carlos Taxonera, David Olivares, Cristina Alba & Juan L. Mendoza

  3. Department of Gastroenterology, Hospital Clínico de Santiago, Santiago de Compostela, Spain

    Manuel Barreiro-de Acosta

  4. Department of Gastroenterology, Hospital Puerta de Hierro, Madrid, Spain

    Marta Calvo

  5. Department of Gastroenterology, Hospital de Cabueñes, Gijón, Spain

    Cristina Saro

  6. Department of Gastroenterology, Hospital La Fe, Valencia, Spain

    Guillermo Bastida

  7. Department of Gastroenterology, Hospital La Paz, Madrid, Spain

    María D. Martín-Arranz

  8. Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain

    Javier P. Gisbert & María Chaparro

  9. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

    Javier P. Gisbert & María Chaparro

  10. Department of Gastroenterology, Hospital Reina Sofía and IMIBIC, Universidad de Córdoba, Córdoba, Spain

    Valle García-Sánchez

  11. Department of Gastroenterology, Hospital Gregorio Marañón, Madrid, Spain

    Ignacio Marín-Jiménez & Celia de Gracia

  12. Department of Gastroenterology, Hospital de Fuenlabrada, Madrid, Spain

    Fernando Bermejo

  13. Department of Gastroenterology, Hospital Infanta Leonor, Madrid, Spain

    Ángel Ponferrada

  14. Department of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain

    María P. Martínez-Montiel

  15. Department of Gastroenterology, Hospital Infanta Sofía, Madrid, Spain

    Ramón Pajares

  16. Inflammatory Bowel Disease Unit, Hospital Universitario Moncloa, Madrid, Spain

    Ignacio Fernández-Blanco

Authors
  1. Carlos Taxonera
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  2. Manuel Barreiro-de Acosta
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  3. Marta Calvo
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  4. Cristina Saro
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  6. María D. Martín-Arranz
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  7. Javier P. Gisbert
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  8. Valle García-Sánchez
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  9. Ignacio Marín-Jiménez
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  12. Ángel Ponferrada
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  13. María P. Martínez-Montiel
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  14. Ramón Pajares
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  15. Celia de Gracia
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  16. David Olivares
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  17. Cristina Alba
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  18. Juan L. Mendoza
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  19. Ignacio Fernández-Blanco
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Corresponding author

Correspondence to Carlos Taxonera.

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Taxonera, C., Barreiro-de Acosta, M., Calvo, M. et al. Infliximab Dose Escalation as an Effective Strategy for Managing Secondary Loss of Response in Ulcerative Colitis. Dig Dis Sci 60, 3075–3084 (2015). https://doi.org/10.1007/s10620-015-3735-4

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  • DOI: https://doi.org/10.1007/s10620-015-3735-4

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