Interleukin 12/interleukin 23 pathway: Biological basis and therapeutic effect in patients with Crohn's disease

Table 1 Summary of randomized, placebo-controlled trials on ustekinumab in Crohn’s disease

Study (reference)	Publication year	Type of publication	Study design	Study phase
Sandborn et al[58]	2008	Full paper	Multicenter, double-blind, placebo-controlled, parallel cross-over	IIa
Sandborn et al[59] (CERTIFI)	2012	Full paper	Randomized, multicenter, double-blind, placebo-controlled	IIb induction
				IIb maintenance
Feagan et al[60] (UNITI-1)	2016	Full paper	Randomized, multicenter, double-blind, placebo-controlled	III
Feagan et al[60] (UNITI-2)	2016	Full paper	Randomized, multicenter, double-blind, placebo-controlled	III
Feagan et al[60] (IM-UNITI)	2016	Full paper	Randomized, multicenter, double-blind, placebo-controlled	Maintenance phase of UNITI 1 and 2 responders
Sandborn et al[63] (IM-UNITI long term extension)	2017	Abstract	Randomized, multicenter, double-blind, placebo-controlled	Maintenance phase of UNITI 1 and 2 responders
Sands et al[62] (UNITI-IM)	2018	Abstract	Randomized, multicenter, double-blind, placebo-controlled	Maintenance phase of UNITI 1 and 2 responders
Rutgeerts et al[61]	2018	Full paper	Randomized, multicenter, double-blind, placebo-controlled	Induction and maintenance of endoscopic healing

Table 2 Characteristics of randomized, placebo-controlled trials evaluating the efficacy of ustekinumab in Crohn’s disease

Study (reference)	Patients	Endpoints	Intervention parameters	Outcomes
Sandbornetal[58]	25	Clinical response at week 4/week 8	90 mg SC week 0-3→Placebo SC week 8-11	Ustekinumab: 53%/49% Placebo: 30%/40%
	26		Placebo SC week 0-3→90mg SC week 8-11
	26		4.5 mg/Kg IV week 0→Placebo IV week 8
	27		Placebo IV week 0→4.5 mg/Kg IV week 8
	27 (primary or secondary non-responders to infliximab)	Clinical response at week 8	90 mg SC	43%
			4.5 mg/kg IV	54%
Sandborn et al[59] (CERTIFI) Induction	131	Clinical response at week 6	1 mg/kg IV	36.60%
	132		3 mg/kg IV	34.10%
	131		6 mg/kg IV	39.70%
	132		Placebo IV	23.50%
Sandborn et al[59] (CERTIFI) Maintenance	145 Responders	Clinical response at week 22	90 mg SC	69.40%
	72 Ustekinumab		Placebo SC	42.50%
	73 Placebo	Clinical remission at week 22	90 mg SC	41.70%
			Placebo SC	27.40%
Feagan et al[60] UNITI-1 induction	245	Clinical response at week 6	130 mg IV	34.30%
	249		6 mg/kg IV	33.70%
	247		Placebo IV	21.50%
Feagan et al[60] UNITI-2 induction	209	Clinical response at week 6	130 mg IV	51.70%
	209		6 mg/kg IV	55.50%
	210		Placebo IV	28.70%
Feagan et al[60] IM- UNITI maintenance	132	Clinical remission at week 44	90 mg SC every 8 wk	53.10%
	132		90 mg SC every 12 wk	48.80%
	133		Placebo SC	35.90%
Sandborn et al[63] (IM- UNITI long term extension)	1281	Clinical remission at week 92	90 mg SC every 8 wk	74.40%
			90 mg SC every 12 wk	72.60%
			Subjects with prior dose adjustment	53.50%
			All ustekinumab treated	67.50%
Sands et al[62] (IM-UNITI patients with dose adjustment following loss of response)	51	Clinical response [CR-100]1	Placebo to 90 mg SC ustekinumab every 8 wk	71%
	29		Ustekinumab 90 mg SC every 12 wk to ustekinumab 90 mg SC every 8 wk	55%
	28		No dose adjustment	46%
Sands et al[62] (IM-UNITI non-responders during induction phase having an additional SC dose)	467	Clinical response 8 wk after one additional dose	Additional dose of 90 mg SC	50.50%
		Clinical remission 8 wk after one additional dose		28.90%
Rutgeerts et al[61] Induction week 8	155	SES-CD Change from baseline, mean (SD)	130 mg IV/6 mg/kg	-2.8 (8.10)a
	97		Placebo IV	-0.7 (4.97)
Rutgeerts et al[61] Maintenance week 44	47	SES-CD Change from baseline, mean (SD)	90mg SC every 12 wk	-1.5 (4.22)
	74		90mg SC every 8 wk	-3.8 (6.02)
	51		Placebo SC	-2.0 (5.35)

¹CR-100, ≥ 100-point decrease in Crohn's Disease Activity Index;

^aP < 0.05. SC: Subcutaneous; IV: Intravenous; SES-CD: Simplified endoscopic activity score for Crohn’s disease; SD: Standard deviation.