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

Goessens, L.; Colombel, J. -F.; Outtier, A.; Ferrante, M.; Sabino, J.; Judge, C.; Saeidi, R.; Rabbitt, L.; Armuzzi, A.; Domenech, E.; Michalopoulos, G.; Cremer, A.; Garcia-Alonso, F. J.; Molnar, T.; Karmiris, K.; Gecse, K.; Van Oostrom, J.; Lowenberg, M.; Farkas, K.; Atreya, R.; Ribaldone, D. G.; Selinger, C.; Hoentjen, F.; Bihin, B.; Sebastian, S.; Rahier, J. -F.; Baert, F.; Horin, S. B.; Bossuyt, P.; Mas, E. B.; Buckley, M.; Byron, C.; Coe, C.; Doherty, G. A.; Dragoni, G.; Fernandes, S.; Gaya, D. P.; Gleeson, S.; Keogh, A.; Levine, A.; Ortega, T. L.; Lobo, A. J.; Macken, E.; Mccarthy, J.; Noor, N.; O'Toole, A.; Posen, A.; Privitera, G.; Pugliese, D.; Raine, T.; Reenaers, C.; Resal, T.; Scarcelli, A.; Slattery, E.; Strubbe, B.; Sugrue, K.; Groen, M. T.; Vicente, G. T.; Truyens, M.; Viola, A.; Yanai, H.; Zulquernain, S. A.

doi:10.1002/ueg2.12170

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%.