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, João Sabino, Ciaran Judge, Reza Saeidi, Louise Rabbitt, Alessandro Armuzzi, Eugeni Domènech, George Michalopoulos, Anneline Cremer, Francisco Javier García‐Alonso, Tamás Resál, Konstantinos Κarmiris, K Gecse, J Van Oostrom, Mark Löwenberg, Klaudia Farkas, Raja Atreya, Davide Giuseppe Ribaldone, Christian P. Selinger, Frank Hoentjen, Benoît Bihin, Shaji Sebastian, European COMBIO study group, Jean‐François Rahier
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%.