Table 1.

Landmark studies that helped define the use of biologics in CD management

Biologic agent	Study	Recruitment numbers	Treatment groups	Duration of study	Response/remission criteria	Limitations	Milestone achieved
Infliximab	Accent I	580	Infliximab (5 mg/kg OR 10 mg/kg) vs placebo	54 weeks	CDAI score of 70 or more from baseline and at least 25% reduction in total score (at week 2 and week 30)	Efficacy measured by clinical response (CDAI and IBDQ scores)	Infliximab can be used as maintenance treatment
	Accent II	306	Infliximab (5 mg/kg OR 10 mg/kg) vs placebo	54 weeks	50% reduction from baseline in number of draining fistulas at week 10 and 14	Fistula closure assessed by physical examination and symptom report rather than objective radiological evidence	Infliximab can be used to treat rectovaginal fistulas
	Sonic	508	Infliximab (5 mg/kg) and oral placebo, azathioprine (2.5 mg/kg) and intravenous placebo, infliximab (5 mg/kg) and azathioprine (2.5 mg/kg)	50 weeks	CDAI score < 150 points Mucosal healing defined as absence of mucosal ulceration at week 26 Corticosteroid-free remission: no budesonide of >6 mg/day or systemic steroids for minimum 3 weeks.	Unable to conclude if combination therapy is disease modifying No cost analysis	Combination therapy has greatest efficacy in corticosteroid-free remission, followed by infliximab monotherapy
Adalimumab	Classic I	299	Adalimumab (40 mg/20 mg, 80 mg/40 mg, 160 mg/80 mg) at week 0 and 2, vs placebo	4 weeks	Response: CR-70 or CR100 from week 0 in CDAI score Remission: CDAI < 150	Short duration. Efficacy measured by clinical response	High-dose induction of 160 mg/80 mg more efficacious in inducing remission
	Classic II	55	Adalimumab 40 mg every other week or weekly vs placebo	56 weeks		Small sample size unable to determine statistical significance Efficacy measured by clinical response	Adalimumab effective in maintaining remission
	Charm	854	Adalimumab (40 mg weekly or alternate weeks) vs placebo	56 weeks	Response: CR-70 at week 4 Remission: CDAI < 150 at weeks 26 and 56	Efficacy measured by clinical response	Weekly or alternate weekly dosing was equally effective in maintaining remission Can treat fistulas Effective in patients who are intolerant or lost response to infliximab
	Gain	325	Adalimumab (160 mg or 80 mg) at week 0 and 2 vs placebo	4 weeks	Response: CR-70/CR100 Remission: CDAI < 150, steroid discontinuation and fistula remission (absence of drainage)	Efficacy measured by clinical response. Short study duration	Adalimumab can be used as second option if previous anti-TNF treatment failed
	Extend	135	Adalimumab (40 mg) every other week vs placebo	52 weeks	Absence of mucosal ulceration at week 12	Mucosal healing not correlated with histology results	Adalimumab provides early and sustained mucosal healing
	Serene	514	Adalimumab (160 mg at week 1, 2, and 3) vs adalimumab (160 mg/80 mg at week 0 and 2) followed by 40 mg every other week.	12 weeks	CDAI < 150 at week 4 Decrease in SES-CD > 50% from baseline at week 12		Ongoing study
Certolizumab pegol	Precise 1	662	Certolizumab (400 mg at weeks 0, 2, and 4) vs placebo followed by every month.	26 weeks	Response at week 6: CR100 Remission at week 26: CDAI < 150	Efficacy measured by clinical response	Certolizumab provides an early improvement in symptoms.
	Precise 2	668	After initial certolizumab (400 mg weeks 0, 2, and 4): 400 mg certolizumab vs placebo every month.	26 weeks		Efficacy measured by clinical response	Certolizumab effective in inducing remission.
Vedolizumab	Gemini 2	185	Vedolizumab 2 mg/kg, 0.5 mg/kg vs placebo at days 1 and 29.	180 days	Response at week 6: CR100 Remission at week 56: CDAI < 150	Efficacy measured by clinical response, small sample size in each arm of study.	Vedolizumab can provide induction and maintenance therapy.
	Gemini 3	315	Vedolizumab 300 mg vs placebo at weeks 0, 2, and 6.	10 weeks	Remission at week 6: CDAI < 150	Short study duration, efficacy measured by clinical response.	Vedolizumab provides a modest benefit in inducing remission in patients who previously failed anti-TNF therapy
Ustekinumab	UNITI-1	741	Ustekinumab 130 mg vs 6 mg/kg vs placebo at week 0. All patients non-responses to anti-TNF therapy.	8 weeks	CR\100 or CDAI < 150 at week 6	Efficacy measured by clinical response	Effective induction of remission following previous non-response to anti-TNF therapy.
	UNITI-2	628	Ustekinumab 130 mg vs 6 mg/kg vs placebo at week 0. All patients failed immunosuppressants or glucocorticoid therapy.	8 weeks		Efficacy measured by clinical response	Effective induction of remission following previous immunosuppression or glucocorticoid failure.
	IM-UNITI	397	Ustekinumab 90 mg every 8 weeks vs 90 mg every 12 weeks vs placebo in patients who responded in UNIT-1/2.	44 weeks	CDAI < 150 at week 44	Efficacy measured by clinical response	Ustekinumab is an effective maintenance therapy.