Precision medicine in inflammatory bowel disease: Individualizing the use of biologics and small molecule therapies

Table 2 Publications of dual biologics

Ref.	Type	Number of participants/IBD type	Biologic combinations	Therapy duration or follow up (mo)	Outcomes
Buer et al[97], 2018	Case series, prospectively followed	Adult: 10 (4 CD, 6 UC)	Anti-TNF, adding on vedolizumab. Combination was intended as a bridging therapy	12-20	Clinical: HBI, PMS, 100 % CRem, 50% endoscopic remission. No serious AE (3 minor infections)
Olbjørn et al[98], 2020	Case series	Pediatric: 13 (9 CD, 4 UC)	Anti-TNF + vedolizumab (8), anti-TNF + ustekinumab (5), (for anti-TNF side effects)	N/A	3/8 (37.5%) Clinical and biochemical remission
Kwapisz et al[99], 2021	Case series	Adult: 15 (14 CD, 1 UC)	8 vedolizumab + anti-TNF, 2 ustekinumab + anti-TNF, 5 vedolizumab + ustekinumab	24	73% CRes, 44% ERes, 27% SE, 20% surgery
Yang et al[100], 2020	Retrospective cohort	Adult: 22 (CD)	24 combinations: 13 vedolizumab + anti-TNF, 8 vedolizumab + ustekinumab, 3 ustekinumab + anti-TNF	1	Endoscopic, PRO2 response/remission, CRP, 50% CRes, 36% SF CRem, 43% ERes, 4% SE (1 SLE-1 cancer), 33% surgery
Glassner et al[101], 2020	Retrospective cohort	50	53 combinations: 25 vedolizumab + ustekinumab, multiple other combinations	5.5-13	50% CRem, 34% ERem, 16% SE, 12% surgery
Privitera et al[102], 2020	Case series, indication active IBD and active EIM	Adult: 16 (11 CD, 4 UC)	Variety of combinations. Most frequent: 3 vedolizumab + adalimumab, 3 vedolizumab + ustekinumab	0.5	At 6 mo: Response IBD/EIM: 42.8%, 11%; Remission IBD/EIM: 14.2%, 55.5%, AE: 3/16 (18.8%)
Dolinger et al[103], 2021	Case series	Pediatric: 16: (CD 7, UC 8, IBD-U 1)	Vedolizumab + ustekinumab, vedolizumab + tofacitinib, ustekinumab + tofacitinib	6	SF remission at 6 mo 12/16 (75%)
Goessens et al[104], 2021	Retrospective cohort, heterogenous, active IBD and/or EIM	Adult: 98 (CD 58, UC 40)	Anti-TNF + vedolizumab, anti-TNF + anti-IL, anti-IL + vedolizumab, tofacitinib + anti-TNF, tofacitinib + vedolizumab, anti-IL + anti-IL, others	5-16	PGA: Complete or partial improvement was observed in 21/80 (26%) and 35/80 (44%); Mean clinical disease activity for IBD: Significantly higher prior to combination than during combination (2.2 +/- 0.7 vs 1.2 +/- 1.1; P < 0.0001). Simple clinical activity scores (quiescent scores 0, mild scores 1, moderate scores 2 and severe scores 3

AE: Adverse events; CD: Crohn’s disease; CRes: Clinical response; CRem: Clinical remission; EIM: Extraintestinal manifestations; ERem: Endoscopic remission; ERes: Endoscopic response; HBI: Harvey Bradshaw index; IBD: Inflammatory bowel disease; IL: Interleukin; N/A: Not applicable; PGA: Physician global assessment; PMS: Partial Mayo score; PRO2: Patient reported outcome scores; SE: Serious infection; SF: Steroid free; TNF: Tumor necrosis factor; UC: Ulcerative colitis.