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Digestive Diseases and Sciences

, Volume 62, Issue 2, pp 481–490 | Cite as

Adalimumab Maintenance Treatment in Ulcerative Colitis: Outcomes by Prior Anti-TNF Use and Efficacy of Dose Escalation

  • Carlos Taxonera
  • Eva Iglesias
  • Fernando Muñoz
  • Marta Calvo
  • Manuel Barreiro-de Acosta
  • David Busquets
  • Xavier Calvet
  • Antonio Rodríguez
  • Ramón Pajares
  • Javier P. Gisbert
  • Pilar López-Serrano
  • José Luís Pérez-Calle
  • Ángel Ponferrada
  • Cristóbal De la Coba
  • Fernando Bermejo
  • María Chaparro
  • David Olivares
  • Cristina Alba
  • Ignacio Fernández-Blanco
Original Article

Abstract

Background

The impact of prior anti-TNF use on “real-life” outcomes of adalimumab therapy in ulcerative colitis (UC) is not well known.

Aim

To compare the influence of prior anti-TNF use on the outcomes of adalimumab maintenance treatment in UC patients. We also assessed the effectiveness of adalimumab dose escalation.

Methods

This retrospective multicenter cohort study included consecutive UC who advanced to an adalimumab maintenance regimen. Patients in whom adalimumab was discontinued prior to week eight of treatment were excluded. The co-primary efficacy endpoints were the cumulative probabilities of adalimumab failure-free survival and colectomy-free survival. We also assessed the need for and the effectiveness of adalimumab dose escalation.

Results

Of 184 UC on maintenance treatment with adalimumab, 116 (63%) had previous anti-TNF use. After a median follow-up of 23 months (interquartile range 13–49), 112 patients (60%) maintained corticosteroid-free clinical response. Sixty-nine patients (37%) had adalimumab failure, and 22 (12%) needed colectomy. Anti-TNF-naïve patients had significantly lower adjusted rates of adalimumab failure (hazard ratio [HR] 0.65; p < 0.001), adalimumab dose escalation (HR 0.35; p = 0.002), and need for colectomy (HR 0.26; p < 0.004). Seventy-six patients (41%) needed dose escalation after secondary loss of response, and 47% of these regained response after escalation. Short-term response after escalation was identified as a significant predictor of colectomy avoidance (HR 0.53; p = 0.007).

Conclusions

In this “real-life” cohort of UC patients on maintenance treatment with adalimumab, anti-TNF-naïve patients had significantly better long-term outcomes. Adalimumab dose escalation enabled recovery of response in nearly half of patients.

Keywords

Ulcerative colitis Adalimumab Infliximab Secondary loss of response Dose escalation Colectomy 

Notes

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.

Compliance with ethical standards

Conflict of interest

CT, MB, AR, JLP, AP, FB, and IF have served as a speaker and/or consultant for or have received research funding from MSD and AbbVie. FM, MC, XC, JPG, and MCH have served as a speaker and/or consultant for or have received research funding from MSD, AbbVie, and Takeda. CdeC have served as a speaker and/or consultant for AbbVie. The remaining authors declare that they have nothing to disclose.

References

  1. 1.
    Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011;60:780–787.CrossRefPubMedGoogle Scholar
  2. 2.
    Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142:257–265.CrossRefPubMedGoogle Scholar
  3. 3.
    García-Bosch O, Gisbert JP, Cañas-Ventura A, et al. Observational study on the efficacy of adalimumab for the treatment of ulcerative colitis and predictors of outcome. J Crohns Colitis. 2013;7:717–722.CrossRefPubMedGoogle Scholar
  4. 4.
    Armuzzi A, Biancone L, Daperno M, et al. Adalimumab in active ulcerative colitis: a ‘real-life’ observational study. Dig Liver Dis. 2013;45:738–743.CrossRefPubMedGoogle Scholar
  5. 5.
    Bálint A, Farkas K, Palatka K, et al. Efficacy and safety of adalimumab in ulcerative colitis refractory to conventional therapy in routine clinical practice. J Crohns Colitis. 2016;10:26–30.CrossRefPubMedGoogle Scholar
  6. 6.
    Hussey M, Mc Garrigle R, Kennedy U, et al. Long-term assessment of clinical response to adalimumab therapy in refractory ulcerative colitis. Eur J Gastroenterol Hepatol. 2016;28:217–221.PubMedGoogle Scholar
  7. 7.
    Barreiro-de Acosta M, Sierra M, Muñoz F, et al. Efficacy of adalimumab (ADA) therapy in patients with steroid-dependent ulcerative colitis (UC). Gastoenterology. 2015;148:S872.CrossRefGoogle Scholar
  8. 8.
    Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19:35–36.CrossRefGoogle Scholar
  9. 9.
    von Elm E, Altman DG, Egger M, STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;20:1453–1457.CrossRefGoogle Scholar
  10. 10.
    Colombel JF, Sandborn WJ, Ghosh S, et al. Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: data from ULTRA 1, 2, and 3. Am J Gastroenterol. 2014;109:1771–1780.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Sandborn WJ, Colombel JF, D’Haens G, et al. One-year maintenance outcomes among patients with moderately-to-severely active ulcerative colitis who responded to induction therapy with adalimumab: subgroup analyses from ULTRA 2. Aliment Pharmacol Ther. 2013;37:204–213.CrossRefPubMedGoogle Scholar
  12. 12.
    Taxonera C, Estelles J, Fernandez-Blanco I, et al. Adalimumab induction and maintenance therapy for patients with ulcerative colitis previously treated with infliximab. Aliment Pharmacol Ther. 2011;33:340–348.CrossRefPubMedGoogle Scholar
  13. 13.
    Baert F, Vande Casteele N, Tops S, et al. Prior response to infliximab and early serum drug concentrations predict effects of adalimumab in ulcerative colitis. Aliment Pharmacol Ther. 2014;40:1324–1332.CrossRefPubMedGoogle Scholar
  14. 14.
    Gisbert JP, Marín AC, McNicholl AG, Chaparro M. Systematic review with meta-analysis: the efficacy of a second anti-TNF in patients with inflammatory bowel disease whose previous anti-TNF treatment has failed. Aliment Pharmacol Ther. 2015;41:613–623.CrossRefPubMedGoogle Scholar
  15. 15.
    García-Bosch O, Aceituno M, Ordás I, et al. Long-term follow-up of patients treated with infliximab for ulcerative colitis: predictive factors of response—an observational study. Dig Dis Sci. Epub. 2/26/2016.Google Scholar
  16. 16.
    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. 2015;60:3075–3084.CrossRefPubMedGoogle Scholar
  17. 17.
    Wolf D, D’Haens G, Sandborn WJ, et al. Escalation to weekly dosing recaptures response in adalimumab-treated patients with moderately to severely active ulcerative colitis. Aliment Pharmacol Ther. 2014;40:486–497.PubMedGoogle Scholar
  18. 18.
    Black CM, Yu E, McCann E, Kachroo S. Dose escalation and healthcare resource use among ulcerative colitis patients treated with adalimumab in English hospitals: an analysis of real-world data. PLoS ONE. 2016;11:e0149692. doi: 10.1371/journal.pone.0149692.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Roblin X, Rinaudo M, Del Tedesco E, et al. Development of an algorithm incorporating pharmacokinetics of adalimumab in inflammatory bowel diseases. Am J Gastroenterol. 2014;109:1250–1256.CrossRefPubMedGoogle Scholar
  20. 20.
    Bank S, Andersen PS, Burisch J, et al. Associations between functional polymorphisms in the NFκB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease. Pharmacogenom J. 2014;14:526–534.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Carlos Taxonera
    • 1
    • 2
  • Eva Iglesias
    • 3
  • Fernando Muñoz
    • 4
  • Marta Calvo
    • 5
  • Manuel Barreiro-de Acosta
    • 6
  • David Busquets
    • 7
  • Xavier Calvet
    • 8
    • 9
  • Antonio Rodríguez
    • 10
  • Ramón Pajares
    • 11
  • Javier P. Gisbert
    • 8
    • 12
  • Pilar López-Serrano
    • 13
  • José Luís Pérez-Calle
    • 13
  • Ángel Ponferrada
    • 14
  • Cristóbal De la Coba
    • 15
  • Fernando Bermejo
    • 16
  • María Chaparro
    • 8
    • 12
  • David Olivares
    • 1
    • 2
  • Cristina Alba
    • 1
    • 2
  • Ignacio Fernández-Blanco
    • 17
  1. 1.Inflammatory Bowel Disease Unit, Department of GastroenterologyHospital Clínico San CarlosMadridSpain
  2. 2.Instituto de Investigación Sanitaria San Carlos (IdISSC)MadridSpain
  3. 3.Hospital Reina SofiaCórdobaSpain
  4. 4.Hospital Virgen BlancaLeónSpain
  5. 5.Hospital Puerta de HierroMadridSpain
  6. 6.Hospital ClínicoSantiago de CompostelaSpain
  7. 7.Hospital Josep TruetaGironaSpain
  8. 8.Corporació Sanitària Universitària Parc TaulíSabadellSpain
  9. 9.Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)MadridSpain
  10. 10.Hospital ClínicoSalamancaSpain
  11. 11.Hospital Infanta SofiaMadridSpain
  12. 12.Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP)MadridSpain
  13. 13.Hospital Universitario Fundación AlcorcónMadridSpain
  14. 14.Hospital Infanta LeonorMadridSpain
  15. 15.Hospital de CabueñesGijónSpain
  16. 16.Hospital de FuenlabradaMadridSpain
  17. 17.Hospital MoncloaMadridSpain

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