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Impact of comorbidities on anti-TNFα response and relapse in patients with inflammatory bowel disease: the VERNE study
  1. Ignacio Marin-Jimenez1,2,
  2. Guillermo Bastida3,
  3. Ana Forés4,
  4. Esther Garcia-Planella5,
  5. Federico Argüelles-Arias6,
  6. Pilar Sarasa7,
  7. Ignacio Tagarro7,
  8. Alonso Fernández-Nistal7,
  9. Carmen Montoto7,
  10. Mariam Aguas3,
  11. Javier Santos-Fernández8,
  12. Marta Maia Bosca-Watts9,
  13. Rocio Ferreiro10,
  14. Olga Merino11,
  15. Xavier Aldeguer12,
  16. Xavier Cortés13,
  17. Beatriz Sicilia14,
  18. Francisco Mesonero15,
  19. Manuel Barreiro-de Acosta16
  1. 1Department of Gastroenterology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
  2. 2Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
  3. 3Department of Gastroenterology, Hospital La Fe, Valencia, Spain
  4. 4Department of Gastroenterology, Hospital General de Castellón, Castellón, Spain
  5. 5Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  6. 6Department of Gastroenterology, Hospital Universitario Virgen Macarena, Sevilla, Spain
  7. 7Medical Department, Takeda Farmacéutica España SA, Madrid, Spain
  8. 8Department of Gastroenterology, Hospital Universitario Río Hortega, Valladolid, Spain
  9. 9IBD Unit, Gastroenterology Department, University Clinic Hospital of Valencia, Valencia, Spain
  10. 10Department of Gastroenterology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
  11. 11Department of Gastroenterology, Hospital Universitario Cruces, Bilbao, Spain
  12. 12Department of Gastroenterology, Hospital Universitari de Girona Doctor Josep Trueta, Girona, Spain
  13. 13IBD Unit, Gastroenterology Section, Internal Medicine, Hospital de Sagunto, Sagunto, Spain
  14. 14Department of Gastroenterology, Hospital Universitario de Burgos, Burgos, Spain
  15. 15Department of Gastroenterology, Hospital Ramon y Cajal, Madrid, Spain
  16. 16Department of Gastroenterology, Hospital Clínico Universitario de Santiago de Compostela, Madrid, Spain
  1. Correspondence to Dr Ignacio Marin-Jimenez; drnachomarin{at}


Objective To evaluate the impact of comorbidities and extraintestinal manifestations of inflammatory bowel disease on the response of patients with inflammatory bowel disease to antitumour necrosis factor alpha (anti-TNFα) therapy.

Design Data from 310 patients (194 with Crohn’s disease and 116 with ulcerative colitis) treated consecutively with the first anti-TNFα in 24 Spanish hospitals were retrospectively analysed. Univariate and multivariate logistic regression analyses were performed to assess the associations between inflammatory bowel disease comorbidities and extraintestinal manifestations with anti-TNFα treatment outcomes. Key clinical features, such as type of inflammatory bowel disease and concomitant treatments, were included as fixed factors in the model.

Results Multivariate logistic regression analyses (OR, 95% CI) showed that chronic obstructive pulmonary disease (2.67, 1.33 to 5.35) and hepato-pancreato-biliary diseases (1.87, 1.48 to 2.36) were significantly associated with primary non-response to anti-TNFα, as was the use of corticosteroids and the type of inflammatory bowel disease (ulcerative colitis vs Crohn’s disease). It was also found that myocardial infarction (3.30, 1.48 to 7.35) and skin disease (2.73, 1.42 to 5.25) were significantly associated with loss of response, along with the use of corticosteroids and the type of inflammatory bowel disease (ulcerative colitis vs Crohn’s disease).

Conclusions Our results suggest that the presence of some comorbidities in patients with inflammatory bowel disease, such as chronic obstructive pulmonary disease and myocardial infarction, and of certain extraintestinal manifestations of inflammatory bowel disease, such as hepato-pancreato-biliary conditions and skin diseases, appear to be related to failure to anti-TNFα treatment. Therefore, their presence should be considered when choosing a treatment.

Trial registration number NCT02861118.

  • TNF-alpha
  • immune response
  • Crohn's disease
  • ulcerative colitis

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  • Contributors All authors have contributed to and agreed on the content of the manuscript: IM-J, GB, AF, EG-P, FA-A, MA, JS-F, MMB-W, RF, OM, XA, XC, BS, FM, and MB-A contributed to study design, patient recruitment, data collection and results interpretation. IT, AF-N, PS, and CM contributed to data analysis and interpretation, drafting of the report, and reviewed it critically. All authors approved the final version of the manuscript.

  • Funding The VERNE study was funded by Takeda Farmacéutica España SA.

  • Competing interests IM-J has served as a consultant, advisory member, speaker, or has received research funding from MSD, AbbVie, Takeda, Tillotts, Ferring, Falk Pharma, Faes Farma, UCB Pharma, Otsuka Pharmaceutical, Shire, Gebro Pharma, and Chiesi. GB has received a speaker honorarium from AbbVie, Pfizer, Janssen, FAES, Takeda, Tillotts and Abbott. Also, GB has participated in the scientific advisory committees of Takeda, Janssen and AbbVie. EG-P has served as a speaker or received research or educational funding or advisory fees from MSD, AbbVie, Janssen, Ferring, Shire, Tillotts, and FAES. FA-A has served as a speaker, a consultant and as an advisory member for or have received research funding from Janssen, MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Sandoz, Takeda, Ferring, Faes Farma, Shire Pharmaceuticals, Dr Falk Pharma, Tillotts Pharma, Gebro Pharma, Amgen and Vifor Pharma. IT, AF-N, and CM are full employees of Takeda Farmacéutica España. PS was a Takeda Farmacéutica España employee at the moment this work was conducted. MA has served as a speaker for MSD, AbbVie, Janssen, Takeda and Tillotts, and received educational grants from Janssen, MSD and AbbVie. JS-F has nothing to declare. MMB-W declares educational activities, research projects, scientific meetings and advisory boards sponsored by MSD, Ferring, AbbVie, Janssen and Takeda. RF has served as a speaker for or has received research funding from Takeda, MSD, AbbVie, Janssen, Palex, Shire Pharmaceuticals, Tillotts Pharma and Casen Recordati. OM has nothing to declare. MB-A has served as a speaker, a consultant and advisory board member for, or has received research funding from, MSD, AbbVie, Janssen, Pfizer, Kern Pharma, Biogen, Takeda, Ferring, Faes Farma, Shire Pharmaceuticals, Dr Falk Pharma, Tillotts Pharma, Chiesi, Gebro Pharma, Otsuka Pharmaceutical and Vifor Pharma.

  • Patient consent for publication Not required.

  • Ethics approval The study was reviewed and approved by the corresponding ethics committees.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. The data that support the findings of this study are available from the sponsor upon request.

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