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Correlation Between Anti-TNF Serum Levels and Endoscopic Inflammation in Inflammatory Bowel Disease Patients

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Abstract

Objectives

(a) To evaluate the diagnostic accuracy of anti-TNF trough levels to predict mucosal healing in inflammatory bowel disease (IBD); (b) to determine the best cut-off point to predict mucosal healing in IBD patients treated with anti-TNF.

Methods

This is a multicenter, prospective study. IBD patients under anti-TNF treatment for at least 6 months that had to undergo an endoscopy were included. Mucosal healing was defined as: Simple endoscopic score for Crohn’s Disease < 3 for Crohn’s disease (CD), Rutgeerts score < i2 for CD in postoperative setting, or Mayo endoscopic score ≤ 1 for ulcerative colitis (UC). Anti-TNF concentrations were measured using SMART ELISAs at trough.

Results

A total of 182 patients were included. Anti-TNF trough levels were significantly higher among patients that had mucosal healing than among those who did not. The area under the curve of infliximab for mucosal healing was 0.63 (best cutoff value 3.4 μg/mL), and for adalimumab 0.60 (best cutoff value 7.2 μg/mL). In the multivariate analysis, having anti-TNF drug levels above the cutoff values [odds ratio (OR) 3.1]) and having UC instead of CD (OR 4) were associated with a higher probability of having mucosal healing. Additionally, the need for an escalated dosage (OR 0.2) and current smoking habit (OR 0.2) were also associated with a lower probability of mucosal healing.

Conclusions

There was an association between anti-TNF trough levels and mucosal healing in IBD patients; however, the accuracy of the determination of infliximab and adalimumab concentrations able to predict mucosal healing was suboptimal.

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Abbreviations

IBD:

Inflammatory bowel disease

CD:

Crohn’s disease

UC:

Ulcerative colitis

OR:

Odds ratio

anti-TNF:

Anti-tumor necrosis factor

SD:

Standard deviation

95% CI:

95% confidence interval

ROC:

Receiver operating characteristic curve

AUC:

Area under the curve

PPV:

Positive predictive value

NPV:

Negative predictive value

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Acknowledgments

The authors wish to thank Sanquin for analyzing serum samples.

Funding

This research was funded by grants from the Instituto de Salud Carlos III (FIS.12/02557 and PI13/00041) and the Ministerio de Economía (SAF2014-56642-JIN) from the Spanish Government.

Author information

Authors and Affiliations

  1. Servicio de Aparato Digestivo, Hospital Universitario de La Princesa e Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain

    María Chaparro, David Bernardo, María G. Donday, Ana Garre & Javier P. Gisbert

  2. Servicio de Aparato Digestivo, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain

    Manuel Barreiro-de Acosta & Rocío Ferreiro-Iglesias

  3. Servicio de Aparato Digestivo, Complejo Hospitalario Universitario de Ferrol, Coruña, Spain

    Ana Echarri & Virginia Ollero Pena

  4. Servicio de Farmacia, Hospital Universitario Rio Hortega, Valladolid, Spain

    Rosendo Almendros

  5. Servicio de Aparato Digestivo, Hospital Universitario Rio Hortega, Valladolid, Spain

    Jesús Barrio

  6. Servicio de Aparato Digestivo, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Jordina Llao

  7. Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa and IIS-Aragón, Saragossa, Spain

    Fernando Gomollón

  8. Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Majadahonda, Spain

    Maribel Vera

  9. Servicio de Aparato Digestivo, Hospital Galdakao-Usansolo, Vizcaya, Spain

    José Luis Cabriada

  10. Servicio de Aparato Digestivo, Hospital Universitari de Bellvitge-IDIBELL, Universidad de Barcelona, Barcelona, Spain

    Jordi Guardiola

  11. Servicio de Aparato Digestivo, Hospital Universitario de Fuenlabrada, Madrid, Spain

    Iván Guerra

  12. Servicio de Aparato Digestivo, Hospital Universitari La Fe, Valencia, Spain

    Belén Beltrán

  13. Servicio de Aparato Digestivo, Complejo Hospitalario la Mancha Centro, Ciudad Real, Spain

    Oscar Roncero

  14. Servicio de Aparato Digestivo, Hospital Universitari de Girona Doctor Josep Trueta, Girona, Spain

    David Busquets

  15. Servicio de Aparato Digestivo, Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain

    Carlos Taxonera

  16. Servicio de Aparato Digestivo, Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain

    Xavier Calvet

  17. Servicio de Análisis Clínicos, Hospital Universitario de La Princesa e Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain

    Ana Godino & Ana Díaz

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

    María Chaparro, Fernando Gomollón, Belén Beltrán, Xavier Calvet, David Bernardo, María G. Donday, Ana Garre & Javier P. Gisbert

Authors
  1. María Chaparro
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  2. Manuel Barreiro-de Acosta
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  3. Ana Echarri
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  4. Rosendo Almendros
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  5. Jesús Barrio
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  6. Jordina Llao
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  7. Fernando Gomollón
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  8. Maribel Vera
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  9. José Luis Cabriada
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  10. Jordi Guardiola
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  11. Iván Guerra
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  12. Belén Beltrán
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  13. Oscar Roncero
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  14. David Busquets
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  15. Carlos Taxonera
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  16. Xavier Calvet
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  17. Rocío Ferreiro-Iglesias
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  18. Virginia Ollero Pena
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  19. David Bernardo
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  20. María G. Donday
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  21. Ana Garre
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  22. Ana Godino
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  23. Ana Díaz
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  24. Javier P. Gisbert
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Contributions

M. Chaparro and J.P. Gisbert conceived and designed this study. All the authors participated in the collection of data and samples of patients. M. Chaparro and J.P. Gisbert analyzed and interpreted the results and wrote the manuscript. All the authors critically reviewed the manuscript, and have read and approved the final version of the manuscript.

Corresponding author

Correspondence to María Chaparro.

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Conflict of interest

María Chaparro has served as a speaker, or has received research or education funding from MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, and Tillotts Pharma. Manuel Barreiro-de Acosta has served as a speaker, has served as a consultant and advisory member for, or has received research funding from MSD, AbbVie, Hospira, Takeda, Janssen, Kern, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Chiesi, Gebro Pharma, Otsuka Pharmaceuticals, and Tillotts Pharma. Maribel Vera has served as speaker for Pfizer and a consultant and advisory member for Kern Pharma. Iván Guerra has served as speaker for Pfizer and a consultant and advisory member for Kern Pharma. Carlos Taxonera has served as a speaker, or a consultant and advisory member for MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, and Gebro Pharma. Xavier Calvet has received grants for research from Abbott, MSD, Vifor fees for advisory boards form Abbott, MSD, Takeda and Vifor and has given lectures for Abbott, MSD, Takeda, Shire and Allergan. Rocío Ferreiro-Iglesias has served as a speaker for AbbVie, Shire y MSD. Javier P. Gisbert has served as a speaker, has served as a consultant and advisory member for, or has received research funding from MSD, AbbVie, Hospira, Pfizer, Kern Pharma, Biogen, Takeda, Janssen, Roche, Celgene, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma. The remaining authors declare that they have no conflict of interest.

Additional information

María Chaparro and Javier P. Gisbert are both the guarantors of the article.

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Chaparro, M., Barreiro-de Acosta, M., Echarri, A. et al. Correlation Between Anti-TNF Serum Levels and Endoscopic Inflammation in Inflammatory Bowel Disease Patients. Dig Dis Sci 64, 846–854 (2019). https://doi.org/10.1007/s10620-018-5362-3

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  • DOI: https://doi.org/10.1007/s10620-018-5362-3

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