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,George Michalopoulos,Shaji Sebastian,Francisco Javier García‐Alonso,Reza Saeidi,Davide Giuseppe Ribaldone,Konstantinos Karmiris,Ciaran Judge,Anneline Cremer,Alessandro Armuzzi,Louise Rabbitt,An Outtier,Frank Hoentjen,Raja Atreya,Klaudia Farkas,Mark Löwenberg,Krisztina Gecse,Marc Ferrante,Eugeni Domènech ,J Van Oostrom ,Christian P Selinger ,Jean‐Frédéric Colombel ,João Sabino ,Benoît Bihin ,Tamás Molnár ,Jean–François Rahier

doi:10.1002/ueg2.12170

Abstract

Background and aimsFew 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.MethodsCombination 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.ResultsA 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.ConclusionsCombination 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%.

Highlights

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterised by a widely variable clinical course and heterogeneous presentations including extra‐intestinal manifestations (EIM), mainly rheumatological and dermatological conditions
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
A total of 104 combinations were identified in 98 IBD patients (6 patients received more than one different combination after failing a first combination)

Summary

Introduction

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterised by a widely variable clinical course and heterogeneous presentations including extra‐intestinal manifestations (EIM), mainly rheumatological and dermatological conditions. IMIDs are continuously evolving and there is currently a broad range of approved biologics and small molecules that target different inflammatory pathways.[1] Despite the progress in therapeutic armamentarium, it is still common to come across IBD patients with primary or secondary loss of response to numerous medications or in whom EIM are not properly controlled whilst the IBD is in remission. In this setting, few clinical series reported efficacy and safety outcomes of combining two biologics and/or small molecules in IBD GOESSENS ET AL. Conclusions: Combination of biologics and small molecules in patients with IBD and IMID/EIM seems to be a promising therapeutic strategy but is associated with a risk of opportunistic infections or infections leading to hospitalisation in 10%

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