Safety and efficacy of combining biologics or small molecules for inflammatory bowel disease or immune-mediated inflammatory diseases: A European retrospective observational study

Laurent Goessens; Jean-Frédéric Colombel; An Outtier; Marc Ferrante; Joao Sabino; Ciaran Judge; Reza Saeidi; Louise Rabbitt; Alessandro Armuzzi; Eugeni Domenech; George Michalopoulos; Anneline Cremer; Francisco Javier García-Alonso; Tamas Molnar; Konstantinos Karmiris; Krisztina Gecse; Joep Van Oostrom; Mark Löwenberg; Klaudia Farkas; Raja Atreya; Davide Giuseppe Ribaldone; Christian Selinger; Frank Hoentjen; Benoit Bihin; Shaji Sebastian; European COMBIO study group; Jean-François Rahier

doi:10.1002/ueg2.12170

Safety and efficacy of combining biologics or small molecules for inflammatory bowel disease or immune-mediated inflammatory diseases: A European retrospective observational study

United European Gastroenterol J. 2021 Dec;9(10):1136-1147. doi: 10.1002/ueg2.12170. Epub 2021 Oct 25.

Authors

Laurent Goessens¹, Jean-Frédéric Colombel², An Outtier³, Marc Ferrante³, Joao Sabino³, Ciaran Judge⁴, Reza Saeidi⁵, Louise Rabbitt⁶, Alessandro Armuzzi⁷, Eugeni Domenech⁸, George Michalopoulos⁹, Anneline Cremer¹⁰, Francisco Javier García-Alonso¹¹, Tamas Molnar¹², Konstantinos Karmiris¹³, Krisztina Gecse¹⁴, Joep Van Oostrom¹⁴, Mark Löwenberg¹⁴, Klaudia Farkas¹², Raja Atreya¹⁵, Davide Giuseppe Ribaldone¹⁶, Christian Selinger¹⁷, Frank Hoentjen¹⁸, Benoit Bihin¹⁹, Shaji Sebastian²⁰; European COMBIO study group; Jean-François Rahier¹

Affiliations

¹ Department of Gastroenterology and Hepatology, Centre Hospitalier Universitaire UCL Namur, Yvoir, Belgium.
² Icahn School of Medicine at Mount Sinai, New York, New York, USA.
³ Department of Gastroenterology and Hepatology, KU Leuven, University Hospital Leuven, Leuven, Belgium.
⁴ Department of Gastroenterology, INITIative IBD Research Network, Mercy University Hospital, Cork, Ireland.
⁵ Centre for Colorectal Disease, INITIative IBD Research Network, St Vincent's University Hospital & School of Medicine, University College Dublin, Dublin, Ireland.
⁶ Department of Clinical Pharmacology and Therapeutics, INITIative IBD research network, Galway University Hospital, Galway, Ireland.
⁷ IBD Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
⁸ Gastroenterology Department, Centro de Investigaciones Biomédicas en Red de Enfermedades Hepáticas y Digestivas, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
⁹ Gastroenterology Department, General Hospital of Piraeus 'Tzaneio', Piraeus, Greece.
¹⁰ Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium.
¹¹ Gastroenterology Department, Hospital Universitario Rio Hortega, Valladolid, Spain.
¹² Gastroenterology Unit, First Department of Medicine, University of Szeged, Szeged, Hungary.
¹³ Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Greece.
¹⁴ Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
¹⁵ Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
¹⁶ Department of Medical Sciences, University of Turin, Turin, Italy.
¹⁷ Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
¹⁸ Department of Gastroenterology, Radboud University Medical Center, Nijmegen, The Netherlands.
¹⁹ Department of Statistics, Centre Hospitalier Universitaire UCL Namur, Yvoir, Belgium.
²⁰ Hull University Teaching Hospitals NHS Trust, Hull, UK.

Abstract

Background and aims: Few data are available regarding the combination of biologics or small molecules in inflammatory bowel disease (IBD) patients. We report safety and efficacy of such combinations through a retrospective multicentre series.

Methods: Combination therapy was defined as the concomitant use of two biologics or one biologic with a small molecule. Patient demographics, disease characteristics and types of combinations were recorded. Safety was evaluated according to the occurrence of serious infection, opportunistic infection, hospitalisation, life-threatening event, worsening of IBD or immune-mediated inflammatory diseases (IMID), cancer and death. Efficacy was evaluated as the physician global assessment of the combination and comparison of clinical/endoscopic scores of IBD/IMID activity prior and during combination.

Results: A total of 104 combinations were collected in 98 patients. Concomitant IMID were present in 41 patients. Reasons for starting combination therapy were active IBD (67%), active IMID or extra-intestinal manifestations (EIM) (22%), both (10%) and unclassified in 1. Median duration of combination was 8 months (interquartile range 5-16). During 122 patient-years of follow-up, 42 significant adverse events were observed, mostly related to uncontrolled IBD. There were 10 significant infections, 1 skin cancer and no death. IBD disease activity was clinically improved in 70% and IMID/EIM activity in 81% of the patients. Overall, combination was continued in 55% of the patients.

Conclusions: Combination of biologics and small molecules in patients with IBD and IMID/EIM seems to be a promising therapeutic strategy but is also associated with a risk of opportunistic infections or infections leading to hospitalisation in 10%.

Keywords: biologics; combination therapy; immune mediated inflammatory disease; inflammatory bowel disease; safety; small molecules; treatment.

Publication types

Multicenter Study
Observational Study

MeSH terms

Adolescent
Adult
Biological Products / therapeutic use*
Drug Therapy, Combination
Europe / epidemiology
Female
Humans
Inflammatory Bowel Diseases / drug therapy*
Male
Retrospective Studies
Young Adult

Substances

Biological Products