Instituto de Investigación Sanitaria La Fe (IIS La Fe)
Published January 1, 2026 | Version v1
Journal article Open

Frequency and Effectiveness of Dose Escalation and De-Escalation of Biologic Therapy in Inflammatory Bowel Disease: The RAINBOW-IBD Study of ENEIDA.

Authors/Creators

  • 1. Department of Gastroenterology, Hospital Universitario de Fuenlabrada, Madrid, Spain
  • 2. Department of Gastroenterology, Hospital Clínic i Provincial, Institut D'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and CIBEREHD, Barcelona, Spain
  • 3. Department of Gastroenterology, Hospital Universitario de La Paz, Madrid, Spain
  • 4. Department of Gastroenterology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
  • 5. Department of Gastroenterology, Hospital Universitario Río Hortega, Valladolid, Spain
  • 6. Department of Gastroenterology, Hospital Universitario Ramón y Cajal, Madrid, Spain
  • 7. Department of Gastroenterology, Hospital Clínico Lozano Blesa, Zaragoza, Spain; Department of Gastroenterology, Instituto de investigación Sanitaria de Aragón (IIS) and CIBEREHD, Madrid, Spain
  • 8. Department of Gastroenterology, Hospital Álvaro Cunqueiro, Vigo, Spain
  • 9. Department of Gastroenterology, Complejo Hospitalario Universitario de Canarias, La Laguna, Spain
  • 10. Department of Gastroenterology, Hospital Universitario Miguel Servet, Instituto de investigación Sanitaria de Aragón (IIS), Zaragoza, Spain
  • 11. Department of Gastroenterology, Hospital Universitario de Burgos, Burgos, Spain
  • 12. Department of Gastroenterology, Hospital Universitario Germans Trias i Pujol and Universitat Autònoma de Barcelona, Badalona and CIBEREHD, Madrid, Spain
  • 13. Department of Gastroenterology, Hospital Reina Sofía, IMIBIC and UCO, Córdoba, Spain
  • 14. Department of Gastroenterology, Parc Taulí Hospital Universitari, Institut D'investigació i Innovació Parc Taulí (I3PT-CERCA), Sabadell, Catalunya, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, Madrid, Spain; CIBERehd, Instituto de Salud Carlos III, Barcelona, Spain
  • 15. Department of Gastroenterology, Hospital Clínico de Valencia, Valencia, Spain
  • 16. Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
  • 17. Department of Gastroenterology, Hospital Universitario Fundación de Alcorcón, Madrid, Spain
  • 18. Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  • 19. Department of Gastroenterology, Complejo Asistencial Universitario de León, León, Spain
  • 20. Department of Gastroenterology, Hospital Universitario Puerta de Hierro, Majadahonda, Spain
  • 21. Department of Gastroenterology, Hospital Moisès Broggi, Sant Joan Despí, Spain
  • 22. Department of Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
  • 23. Department of Gastroenterology, Hospital Universitari Consorci Sanitari de Terrassa (CST), Terrassa, Spain
  • 24. Department of Gastroenterology, Hospital Universitario Marqués de Valdecilla and IDIVAL, Santander, Spain
  • 25. Department of Gastroenterology, Hospital Universitari Bellvitge, L'Hospitalet de Llobregat, Spain
  • 26. Department of Gastroenterology, Hospital Universitari Mútua Terrassa, University of Barcelona and CIBEREHD, Madrid, Spain
  • 27. Department of Gastroenterology, Complejo Asistencial de Zamora, Zamora, Spain
  • 28. Department of Gastroenterology, Hospital Universitario de Galdakao, Biobizkaia Health Research Institute, Galdakao, Spain
  • 29. Department of Gastroenterology, Hospital Universitario Infanta Leonor, Madrid, Spain
  • 30. Department of Gastroenterology, Hospital de San Jorge, Huesca, Spain
  • 31. Department of Gastroenterology, Hospital Universitario Nuestra Sra. de la Candelaria, Santa Cruz de Tenerife, Spain
  • 32. Department of Gastroenterology, Hospital del Mar, Barcelona, Spain; Institut Hospital del Mar D'investigacions Mèdiques (IMIM), Barcelona, Spain
  • 33. Department of Gastroenterology, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
  • 34. Department of Gastroenterology, Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
  • 35. Department of Gastroenterology, Hospital Dr. Josep Trueta, Girona, Spain
  • 36. Department of Gastroenterology, Hospital General de Granollers, Barcelona, Spain
  • 37. Department of Gastroenterology, Hospital General Universitario Doctor Balmis e ISABIAL, Alicante and CIBEREHD, Madrid, Spain
  • 38. Department of Gastroenterology, Hospital General Universitario de Elche, Alicante, Spain
  • 39. Department of Gastroenterology, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
  • 40. Department of Gastroenterology, IiSGM, Hospital Gregorio Marañón Medicine Faculty, Complutense University, Madrid, Spain
  • 41. Department of Gastroenterology, Hospital General Universitario de Valencia, Valencia, Spain
  • 42. Department of Gastroenterology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
  • 43. Department of Gastroenterology, Althaia Xarxa Assistencial Universitaria de Manresa, Barcelona, Spain
  • 44. Department of Gastroenterology, Hospital Universitario de Navarra, IdisNA, Navarra, Spain
  • 45. Department of Gastroenterology, Hospital General La Mancha Centro, Alcázar de San Juan, Spain
  • 46. Department of Gastroenterology, Biogipuzkoa Health Research Institute, Universidad del País Vasco (UPV/EHU), San Sebastián and CIBEREHD, Madrid, Spain
  • 47. Department of Gastroenterology, Hospital General de Tomelloso, Ciudad Real, Spain; Department of Gastroenterology, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM) and CIBEREHD, Madrid, Spain
  • 48. Department of Gastroenterology, Hospital Universitari Arnau de Vilanova, Lleida, Spain
  • 49. Department of Gastroenterology, Hospital Universitario de Cáceres, Cáceres, Spain
  • 50. Department of Gastroenterology, Hospital Son Espases, Palma de Mallorca, Spain
  • 51. Department of Gastroenterology, Complexo H. Universitario de Ourense, Ourense, Spain
  • 52. Department of Gastroenterology, Hospital Son Llàtzer, Manacor, Spain
  • 53. Department of Gastroenterology, Hospital Universitario Infanta Sofía, Faculta de Medicina, Universidad Europea de Madrid, San Sebastián de los Reyes, Spain
  • 54. Department of Gastroenterology, Hospital Universitario de Torrejón, Universidad Francisco de Vitoria, Madrid, Spain
  • 55. Department of Gastroenterology, Hospital General de Castelló, Castellón, Spain
  • 56. Department of Gastroenterology, Hospital Virgen de la Luz, Cuenca, Spain
  • 57. Department of Gastroenterology, Hospital de Basurto, Bilbao, Spain
  • 58. Department of Gastroenterology, Hospital Universitario de Cabueñes, Asturias, Spain
  • 59. Department of Gastroenterology, Hospital Universitario Virgen Macarena, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain
  • 60. Department of Gastroenterology, Hospital Universitari i Politècnic la Fe, Valencia, Spain
  • 61. Department of Gastroenterology, Hospital Virgen de la Victoria, Málaga, Spain
  • 62. Department of Gastroenterology, Hospital Santos Reyes, Aranda de Duero, Spain
  • 63. Department of Gastroenterology, Hospital de San Pedro, Logroño, Spain
  • 64. Department of Gastroenterology, Hospital Universitario de Salamanca, Salamanca, Spain
  • 65. Department of Gastroenterology, Hospital Viladecans, Barcelona, Spain
  • 66. Department of Gastroenterology, Hospital Regional Universitario de Málaga, Málaga, Spain
  • 67. Department of Gastroenterology, Hospital Universitario de Áraba, Vitoria-Gasteiz, Álava, Spain
  • 68. Department of Gastroenterology, Hospital Vega Baja, Orihuela, Spain
  • 69. Department of Gastroenterology, Complejo Asistencial de Segovia, Segovia, Spain
  • 70. Department of Gastroenterology, Hospital Joan XXIII, Tarragona, Spain
  • 71. Department of Gastroenterology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
  • 72. Department of Gastroenterology, Hospital Santa Bárbara, Soria, Spain

Description

BACKGROUND: Real-world data on dose escalation/de-escalation in inflammatory bowel disease (IBD) are scarce. AIMS: To assess the frequency, effectiveness and durability of escalation/de-escalation of infliximab, adalimumab, golimumab, vedolizumab and ustekinumab in IBD, and to identify factors influencing relapse and drug discontinuation and re-escalation efficacy. METHODS: We included patients from the ENEIDA registry of GETECCU who were exposed to biologics and analysed escalations/de-escalations. We assessed the impact of variables on durability, drug discontinuation and relapse after escalation/de-escalation. RESULTS: Of 19,720 patients on biologics, 5096 (26%) underwent dose escalation. Frequency of escalation per patient-year was 5% (infliximab), 7% (adalimumab), 7% (golimumab), 10% (vedolizumab) and 12% (ustekinumab). Clinical remission was recaptured in 32%-49% of patients. Durability of escalation (24 months) ranged from 66% to 88%. Drug discontinuation was associated with previous biologic exposure and disease duration (infliximab), monotherapy (adalimumab) and ulcerative colitis (ustekinumab). There were 669 de-escalations. The frequency per patient-year was 6%, 9%, 5%, 6% and 3% for infliximab, adalimumab, golimumab, vedolizumab and ustekinumab. Maintenance of remission after de-escalation was observed in 75%-100%. Durability of de-escalation (12 months) was 82%-90%. Factors associated with relapse were biologic exposure (infliximab) and age at de-escalation (adalimumab). Re-escalation benefited most patients. CONCLUSIONS: In the long term, some patients with IBD need biologic escalation, which frequently recaptures durable clinical remission. De-escalation is feasible in some patients. Re-escalation is generally effective after relapse. © 2025 John Wiley & Sons Ltd.

Notes

Funding text 1: Cristina Rub\u00EDn de C\u00E9lix has received education funding from Ferring, Tillotts Pharma, AbbVie, Sandoz, Alfasigma, Lilly, Norgine, MSD, Pfizer, Takeda and Janssen; Elena Ricart has received support for congress and conference attendance, speaker fees, research support or consulting fees from MSD, AbbVie, Ferring, Janssen, Otsuka, Pfizer, Takeda, Faes Farma, Galapagos, Kern Pharma, Lilly and Fresenius\u2010Kabi; Ruth de Francisco has received support for conference attendance, and research support from AbbVie, Faes Farma, Ferring, Janssen, Pfizer, Takeda and Galapagos; Francisco Javier Garc\u00EDa\u2010Alonso has served as a speaker for Pfizer, Janssen and AbbVie, and has received research funding from Janssen and AbbVie; Fernando Gomoll\u00F3n has served as a speaker, consultant and advisory member for AbbVie and FAES\u2010Farma. Fernando Gomoll\u00F3n has received research or education funding from: AbbVie, Janssen, Pfizer and Takeda; Laura Ramos has served as a speaker, consultant and advisory board member for MSD, Ferring, AbbVie, Pfizer, Adacyte, Takeda and Janssen; Miriam Ma\u00F1osa has served as a speaker, consultant and advisory member for or has received research funding from AbbVie, Galapagos, Janssen, MSD, Pfizer, Faes Farma, Takeda, Tillotts and Dr. Falk Pharma; Eva Iglesias has received financial support for travelling and educational activities from or has served as an advisory board member for AbbVie, Adacyte, Janssen, Pfizer, Takeda and Falk; Mar\u00EDa Jos\u00E9 Casanova has received research or education funding from Pfizer, Takeda, Janssen, MSD, Ferring, AbbVie, Biogen, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi and Norgine; Antonio Giordano received travel grants from Janssen, Falk and Ferring; M\u00F3nica Sierra\u2010Aus\u00EDn has served as a speaker, or has received research or education funding from AbbVie, Pfizer, Takeda, Janssen, Galapagos, Ferring and Tillotts; Isabel Vera has served as a speaker, consultant and advisory member for and has received funding for: MSD, AbbVie, Pfizer, Ferring, Shire Pharmaceuticals, Takeda, Tillotts, Janssen and Gal\u00E1pagos; Rufo Lorente has served as a speaker, or has received research or education funding from AbbVie, Pfizer, Takeda, Janssen and Galapagos; Marta Piqueras has served as a speaker or has received research or education funding from Takeda, AbbVie, FAES Pharma, Galapagos and Janssen; Montserrat Rivero has served as a speaker or advisory member from AbbVie, Lilly, Takeda, Janssen, Galapagos, Ferring and Pfizer; Jordi Guardiola has served as a speaker, or has received research or education funding or advisory fees from Lilly, Roche, MSD, AbbVie, Celltrion, Kern Pharma, GoodGut, Takeda, Janssen, Pfizer, Galapagos, Sandoz, B\u00FClhmann, Ferring and GE Healthcare; Iago Rodr\u00EDguez\u2010Lago has received financial support for travelling and educational activities from or has served as an advisory board member for AbbVie, Adacyte, Alfasigma, Biogen, Celltrion, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, Mirum Pharmaceuticals, MSD, Pfizer, Roche, Takeda and Tillotts Pharma. Research support from AbbVie. Iago Rodr\u00EDguez\u2010Lago is supported by a research grant from Gobierno Vasco\u2010Eusko Jaurlaritza [Grant No 2020111061]; \u00C1ngel Ponferrada\u2010D\u00EDaz has served as a speaker, a consultant or advisory member from AbbVie, Lilly, Takeda, Ferring, Alfasigma and Janssen; Carlos Taxonera has served as a speaker, consultant and advisory board member for MSD, AbbVie, Pfizer, Takeda, Galapagos, Fresenius Kabi, Lilly, Ferring, Faes Farma, Dr. Falk Pharma and Tillotts; Manuel Barreiro\u2010De Acosta has received financial support for travelling and educational activities from or has served as an advisory board member for Pfizer, MSD, Takeda, AbbVie, Kern Pharma, Janssen, Fresenius Kabi, Biogen, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Chiesi, Gebro Pharma, Otsuka Pharmaceuticals and Tillotts Pharma; Jose M. Huguet has served as a speaker and consultant for or has received research funding from MSD, AbbVie, Takeda, Janssen, Pfizer, Ferring, Sandoz, Tillotts Pharma, Dr. Falk Pharma and Faes Farma; Cristina Rodr\u00EDguez\u2010Guti\u00E9rrez has served as a speaker, or has received research or education funding from AbbVie, Pfizer, MSD, Tillotts, Ferring, Lilly, Takeda, Janssen and Galapagos; Ram\u00F3n Pajares has received financial support for travelling from Takeda; Teresa de Jes\u00FAs Mart\u00EDnez\u2010P\u00E9rez reports personal fees or non\u2010financial support from AbbVie, Amgen, MSD, Janssen, Takeda, Pfizer, Chiesi, Tillotts Pharma, Kern Pharma, outside the submitted work; Pilar Nos has served as speaker, consultant and advisory board or has received research funding from MSD, AbbVie, Janssen, Takeda, Biogen, Lilly, Roche, Sandoz, Ferring, Adacyte, Faes Farma, Kern Pharma, Pfizer, Vifor Pharma, Chiesi and Tillotts; Eugeni Dom\u00E8nech has served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Ferring, Galapagos, Gilead, GoodGut, Imidomics, Janssen, Kern Pharma, Lilly, MSD, Pfizer, Roche, Samsung, Takeda, Tillotts; Mar\u00EDa Chaparro has served as a speaker, consultant and advisory member for, or received research funding from, AbbVie, Celltrion, Chiesi, Faes Farma, Dr. Falk Pharma, Ferring, Gebro Pharma, Janssen, MSD, Otsuka Pharmaceuticals, Pfizer Inc., Roche, Shire Pharmaceuticals, Takeda, Tillotts Pharma and Lilly; Javier P. Gisbert has served as speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma. The authors declare no conflicts of interest.; Funding text 2: Funding: Eli Lilly and Company supported the statistical analysis, medical writing and publication fee of this study without being directly involved in any steps of its development (conception and design, analysis or interpretation of the results). ENEIDA Registry is supported by AbbVie, Lilly, Biogen, Gal\u00E1pagos, Pfizer and Takeda.; Funding text 3: We designed a multicentre, cross\u2010sectional study selecting IBD patients included in ENEIDA registry who received biologic agents. ENEIDA registry is a prospectively maintained nationwide database supported by the (GETECCU) [ 12 ]. Our study population comprised patients included in ENEIDA from January 1 2012 to December 28 2022. Spanish Working Group on Crohn's Disease and Ulcerative Colitis; Funding text 4: ENEIDA Registry is supported by AbbVie, Lilly, Biogen, Gal\u00E1pagos, Pfizer and Takeda.

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