Combination treatment of inflammatory bowel disease: Present status and future perspectives

Table 1 Results of clinical trials with dual biologic therapy in patients with active inflammatory bowel disease

Ref.	No. of patients/disease	Kind of DBT	Efficacy	Side-effects
Sands et al[14], 2007	79 (two arms: 52 and 27 respectively) CD	IFX + Natali-zumab vs IFX + placebo	Better results in DBT but not significant	Headache, infections (27%), nausea, nasopharyngitis
Privitera et al[11], 2020	16 (11 with CD & 5 with UC)	anti-TNF + VDZ or UST or VDZ & UST for 8 wk	Clinical improvement (intestinal and extraintestinal manifestations): In all patients	In 3 patients, all non-serious
Glassner et al[12], 2020	50 IBD patients (32 CD, 18 UC)	29 out of 50 patients received DBT	DBT: More patients in clinical and endoscopic remission at follow-up vs baseline	In 26% of pts. Infections: In patients on DBT. Lower risk in those not on a concomitant immunomodulator
Yang et al[15], 2020	22 patients with CD with 24 therapeutic trials of DBT	Six biologic agents were used in: Anti-TNF + UST or VDZ	Endoscopic improvement: In 43% of trials. Endoscopic remission: 26%. Clinical response: 50%. Clinical remission: 41%	Similar rates of adverse events (13% of trials)
Kwapisz et al[13], 2021	15 (14 CD, 1 UC)	Various biologics VDZ + anti-TNF/UST; UST + anti-TNF/VDZ	DBT may be effective. Anti-TNF or VDZ plus UST were most effective	DBT may be safe
Feagan et al[19], 2023	Severe UC	GUS + GOL (71) vs GUS alone (72) vs GOL alone (71 pts)	At week 12, 83% of DBT patients had clinical response vs 61% and 75% on GOL and GUS monotherapy, respectively	At week 50, 63%, 76% and 65% of patients experienced at least one side-effect (infections, fever, nasopharyngitis, neutropenia
Miyatani et al[18], 2024	CD	UPA + UST	5/6 patients, achi-evedremission. Two with severe arthritis: Signifi-cant improvement	Mild respiratory symptoms and nausea

CD: Crohn’s disease; GOL: Golimumab; GUS: Guselkumab, IBD: Inflammatory bowel disease; IFX: Infliximab; TNF: Tumor necrosis factor; UC: Ulcerative colitis; UST: Ustekinumab; UPA: Upadacitinib; VDZ: Vedolizumab; DBT: Dual biologic therapy.

Table 2 Results of clinical trials with combination therapy in patients with active inflammatory bowel disease

Ref.	Disease	Kind of CT	Efficacy
Colombel et al[24], 2015	Severe UC	IFX + AZA vs IFX alone vs AZA alone	CT was more effective compared to monotherapy with AZA or IFX. High rate of mucosal healing with CT
Feagan et al[26], 2014	CD	IFX + MTX vs IFX alone vs MTX alone	No significant differences. Safe combination
Louis et al[29], 2023	CD	IFX + AZA vs AZA alone vs IFX alone	Relapse rate: 12% in the DBT group compared to 35% (IFX group) and 9% in the AZA group. Most frequent side-effects: Infections
Roblin et al[30], 2020	IBD 90 patients	Therapeutic strategies: Change of anti-TNF agent to another or adding immunosuppressant	The rate of clinical failure and occurrence of adverse pharmacokinetic curves were higher in monotherapy compared to CT. Use of CT after switching to the anti-TNF agent is recommended
Matsumoto et al[34], 2016	CD	Monotherapy vs combination group (ADA + AZA vs ADA alone)	Remission rate at week 26 did not differ between the two groups. Thus, combination of ADA with AZA offers no benefit compared to ADA alone
Christensen et al[36], 2019	9 patients with CD and 11 with UC	VDZ + calcineurin inhibitors	CT of VDZ with calcineurin inhibitors is a safe and effective combination to induce remission in IBD
Sands et al[37], 2019	CD	VDZ + CS vs VDZ alone vs CS alone	CT: Higher rates of clinical remission compared to the other groups. Similar adverse events

ADA: Adalimumab; anti-TNF: Anti-tumor necrosis factor; AZA: Azathioprine; CD: Crohn’s disease; CT: Combination treatment; CS: Corticosteroids; IBD: Inflammatory bowel disease; IFX: Infliximab; UC: Ulcerative colitis; VDZ: Vedolizumab; DBT: Dual biologic therapy.