Effectiveness and safety of a third-line rescue treatment for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study)

María José García¹, Sabino Riestra², Aurelien Amiot³, Mette Julsgaard^{4

5}, Irene García de la Filia⁶, Margalida Calafat⁷, Mariam Aguas⁸, Luisa de la Peña⁹, Cristina Roig¹⁰, Berta Caballol¹¹, María José Casanova¹², Klaudia Farkas¹³, Trine Boysen^{14

15

16}, Luis Bujanda¹⁷, Camila Cuarán¹⁸, Daniela Dobru¹⁹, Fotios Fousekis²⁰, Carla Jerusalén Gargallo-Puyuelo²¹, Edoardo Savarino²², Xavier Calvet²³, José María Huguet²⁴, Limas Kupcinskas²⁵, Julia López-Cardona²⁶, Tim Raine²⁷, Joep van Oostrom²⁸, Javier P Gisbert¹², María Chaparro¹²

Affiliations

¹ Gastroenterology and Hepatology Department, Hospital Universitario Marqués de Valdecilla, Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, Instituto de Investigación Valdecilla (IDIVAL), Universidad de Cantabria, Santander, Spain.
² Gastroenterology Department, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.
³ Department of Gastroenterology, CHU Bicêtre, Universite Paris Saclay, Paris, France.
⁴ Department of Gastroenterology and Hepatology, Aarhus University Hospital, Aarhus, Denmark.
⁵ Department of Clinical Medicine, Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Aalborg University, Copenhagen, Denmark.
⁶ Gastroenterology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.
⁷ Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
⁸ Gastroenterology Department, La Fe University and Polytechnic Hospital, Health Research Institute La Fe, Valencia, Spain.
⁹ Gastroenterology Department, Bellvitge University Hospital, Barcelona, Spain.
¹⁰ Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
¹¹ Gastroenterology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
¹² Gastroenterology Department, 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.
¹³ Department of Medicine, University of Szeged, Szeged, Hungary.
¹⁴ Gastro Unit, Medical Division, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
¹⁵ Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
¹⁶ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁷ Department of Gastroenterology, Biodonostia Health Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain.
¹⁸ Gastroenterology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain.
¹⁹ Gastroenterology Department, University of Medicine and Pharmacy, Science and Tehnology "G E Palade" Tg.Mures, Târgu-Mureș, Romania.
²⁰ Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece.
²¹ Department of Gastroenterology, University Clinic Hospital Lozano Blesa, Institute for Health Research Aragón (IIS Aragón), Zaragoza, Spain.
²² Department of Surgery, Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, Azienda Ospedale Università di Padova (AOUP), University of Padua, Padua, Italy.
²³ Gastroenterology Department, Servei d'Aparell Digestiu, Parc Taulí, Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí, Departamento de Medicina, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Sabadell, Spain.
²⁴ Digestive Diseases Department, General University Hospital of Valencia, Valencia, Spain.
²⁵ Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
²⁶ IBD Unit, Guy's and St Thomas' Hospital, London, UK.
²⁷ Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
²⁸ Department of Gastroenterology and Hepatology, Amsterdam UMC, Amsterdam, The Netherlands.

PMID: 38445785
DOI: 10.1111/apt.17938

Multicenter Study

Effectiveness and safety of a third-line rescue treatment for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study)

María José García et al. Aliment Pharmacol Ther. 2024 May.

. 2024 May;59(10):1248-1259.

doi: 10.1111/apt.17938. Epub 2024 Mar 6.

Authors

Affiliations

¹ Gastroenterology and Hepatology Department, Hospital Universitario Marqués de Valdecilla, Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, Instituto de Investigación Valdecilla (IDIVAL), Universidad de Cantabria, Santander, Spain.
² Gastroenterology Department, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.
³ Department of Gastroenterology, CHU Bicêtre, Universite Paris Saclay, Paris, France.
⁴ Department of Gastroenterology and Hepatology, Aarhus University Hospital, Aarhus, Denmark.
⁵ Department of Clinical Medicine, Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Aalborg University, Copenhagen, Denmark.
⁶ Gastroenterology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.
⁷ Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
⁸ Gastroenterology Department, La Fe University and Polytechnic Hospital, Health Research Institute La Fe, Valencia, Spain.
⁹ Gastroenterology Department, Bellvitge University Hospital, Barcelona, Spain.
¹⁰ Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
¹¹ Gastroenterology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
¹² Gastroenterology Department, 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.
¹³ Department of Medicine, University of Szeged, Szeged, Hungary.
¹⁴ Gastro Unit, Medical Division, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
¹⁵ Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
¹⁶ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁷ Department of Gastroenterology, Biodonostia Health Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain.
¹⁸ Gastroenterology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain.
¹⁹ Gastroenterology Department, University of Medicine and Pharmacy, Science and Tehnology "G E Palade" Tg.Mures, Târgu-Mureș, Romania.
²⁰ Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece.
²¹ Department of Gastroenterology, University Clinic Hospital Lozano Blesa, Institute for Health Research Aragón (IIS Aragón), Zaragoza, Spain.
²² Department of Surgery, Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, Azienda Ospedale Università di Padova (AOUP), University of Padua, Padua, Italy.
²³ Gastroenterology Department, Servei d'Aparell Digestiu, Parc Taulí, Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí, Departamento de Medicina, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Sabadell, Spain.
²⁴ Digestive Diseases Department, General University Hospital of Valencia, Valencia, Spain.
²⁵ Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
²⁶ IBD Unit, Guy's and St Thomas' Hospital, London, UK.
²⁷ Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
²⁸ Department of Gastroenterology and Hepatology, Amsterdam UMC, Amsterdam, The Netherlands.

PMID: 38445785
DOI: 10.1111/apt.17938

Abstract

Background: The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) and avoid colectomy.

Aims: To evaluate the colectomy-free survival and safety of a third-line treatment in patients with ASUC refractory to intravenous steroids and who failed either infliximab or ciclosporin.

Methods: Multicentre retrospective cohort study of patients with ASUC refractory to intravenous steroids who had failed infliximab or ciclosporin and received a third-line treatment during the same hospitalisation. Patients who stopped second-line treatment due to disease activity or adverse events (AEs) were eligible. We assessed short-term colectomy-free survival by logistic regression analysis. Kaplan-Meier curves and Cox regression models were used for long-term assessment.

Results: Among 78 patients, 32 received infliximab and 46 ciclosporin as second-line rescue treatment. Third-line treatment was infliximab in 45 (58%), ciclosporin in 17 (22%), tofacitinib in 13 (17%) and ustekinumab in 3 (3.8%). Colectomy was performed in 29 patients (37%) during follow-up (median 21 weeks). Of the 78 patients, 32 and 18 were in clinical remission at, respectively, 12 and 52 weeks. At the last visit, 25 patients were still on third-line rescue treatment, while 12 had stopped it due to clinical remission. AEs were reported in 26 (33%) patients. Two patients died (2.6%), including one following colectomy.

Conclusion: Third-line rescue treatment avoided colectomy in over half of the patients with ASUC and may be considered a therapeutic strategy.

PubMed Disclaimer

Comment in

Editorial: Sequencing rescue therapy for acute severe ulcerative colitis-Ready for revision?
Derikx LAAP, Hoentjen F. Derikx LAAP, et al. Aliment Pharmacol Ther. 2024 May;59(10):1296-1297. doi: 10.1111/apt.17973. Aliment Pharmacol Ther. 2024. PMID: 38652770 No abstract available.
Letter: Third-line therapy in acute severe ulcerative colitis, exploring the uncertainty and unanswered questions.
Chetwood JD, Ding NS. Chetwood JD, et al. Aliment Pharmacol Ther. 2024 Jul;60(2):298-299. doi: 10.1111/apt.18056. Epub 2024 Jun 3. Aliment Pharmacol Ther. 2024. PMID: 38828835 No abstract available.

References

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1. Hindryckx P, Jairath V, D'Haens G. Acute severe ulcerative colitis: from pathophysiology to clinical management. Nat Rev Gastroenterol Hepatol. 2016;13(11):654–664.
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Effectiveness and safety of a third-line rescue treatment for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study)

Affiliations

Effectiveness and safety of a third-line rescue treatment for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study)

Authors

Affiliations

Abstract

Comment in

References

REFERENCES

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LinkOut - more resources

Full Text Sources

Medical