Role of the combination of biologics and/or small molecules in the treatment of patients with inflammatory bowel disease

Table 1 Publications including 2 or more adult or pediatric inflammatory bowel disease patients with use of combination therapy

Ref.	Study type (type of patients)	Disease (number of patients)	Combinations	Efficacy	Adverse events
Sands et al[20], 2007	Randomized controlled trial (adults)	CD (52)	NAT + IFX	Remission 37%	Headache, CD exacerbation, nausea, nasopharyngitis
Buer et al[22], 2018	Prospective cohort (adults)	CD (4), UC (6)	9 IFX + VDZ, 1 ADA + UST	Remission 100 %	3 upper airway infections
Mao et al[23], 2018	Case series (adults)	CD (4)	1 TNFi + UST/VDZ, 1 VDZ + UST, 2 VDZ + GOL	Remission 3/4	1 hand, foot and mouth disease, 1 influenza, 1 Clostridiodes difficile
Kwapisz et al[24], 2020	Retrospective cohort (adults)	CD (14), UC (1)	8 VDZ + TNFi, 5 VDZ + UST, 2 UST + TNFi	Improvement 11/15	Salmonella, Clostridiodes difficile, 4 infections, arthralgia
Olbjørn et al[25], 2020	Retrospective cohort (pediatrics)	CD (9), UC (4)	8 IFX + VDZ, 5 IFX + UST	Remission 9/13	Elevated transaminases, eczema, skin infection
Fumery et al[26], 2020	Case series (adults)	CD (5), UC (2)	5 TNFi + UST, 2 TNF + VDZ	Remission 6/7	No
Glassner et al[27], 2020	Retrospective cohort (adults)	CD (30), UC (18), IBD-U (1)	7 VDZ + TNFi, 25 VDZ + UST, 9 TOF + TNFi, 8 TOF + VDZ, 3 TOF + UST	Remission 50%	3 bacterial enteric infections (E. coli), 3 Clostridiodes difficile, 1 peristomal cellulitis, 2 abdominal wall abscesses
Privitera et al[28], 2020	Retrospective cohort (adults)	CD (11), UC (5)	3 VDZ + UST, 9 VDZ + TNFi/other, 3 VDZ + UST	Clinical response 43%	1 cutaneous reaction, 1 drug-induced liver injury, 1 perianal abscess
Yang et al[29], 2020	Retrospective cohort (adults)	CD (22)	8 VDZ + UST, 13 VDZ + TNFi, 3 UST + TNFi	Remission 41%	1 drug induced lupus, 1 pneumonia, 1 Clostridiodes difficile, 1 acinetobacter bacteremia
Alayo et al[30], 2021	Retrospective cohort (adults)	CD (10), UC (25)	24 VDZ + TOF, 5 TOF + UST	Remission 70% at 26 wk	1 Clostridiodes difficile, 1 candida esophagitis, 1 abnormal lipid profile
Dolinger et al[31], 2021	Retrospective cohort (pediatrics)	CD (7), UC (8), IBD-U (1)	9 VDZ + TOF, 4 VDZ + UST, 3 UST + TOF	Remission 12/16	1 septic arthritis, 1 deep vein thrombosis
Llano et al[32], 2021	Retrospective cohort (adults)	CD (3), UC (10), IBD-U (1)	3 UST + VDZ, 2 VDZ + TNFi, 9 VDZ + TOF	Clinical or biochemical remission 50%	2 Clostridiodes difficile, 2 pneumonia, 3 abnormal lipid profile
Goessens et al[33], 2021	Retrospective cohort (adults)	CD (58), UC (40)	41 VDZ + TNFi, 21 VDZ + UST, 11 UST + TNFi, 1 TOF + TNFi, 13 TOF + VDZ, 17 other	Clinical response 44%	10 serious or opportunistic infections
Howard et al[34], 2022	Case series (pediatrics)	CD (3)	3 VDZ + UST	Clinical remission 100%	Not reported
Lee et al[35], 2022	Retrospective cohort (adults)	CD (19)	7 TOF + VDZ, 11 TOF + UST, 1 TOF + TNFi	Remission 60%	1 basal cell carcinoma

ADA: Adalimumab; CD: Crohn’s disease; GOL: Golimumab; IBD-U: Inflammatory bowel disease-unclassified; IFX: Infliximab; NAT: Natalizumab; TNFi: Tumor necrosis factor inhibitor; TOF: Tofacitinib; UC: Ulcerative colitis; UST: Ustekinumab; VDZ: Vedolizumab.