Reviewing treatments and outcomes in the evolving landscape of ulcerative colitis

Figures & data

Table 1. Instruments used in the evaluation of disease severity in clinical trials of UC.

Instrument	Components and scoring
Truelove and Witts [13]	Mild: mild diarrhea (≤4 BM/d) with only small amounts of macroscopic blood in stool; no fever; no tachycardia; no severe anemia; ESR ≤30 mm/h
	Moderate: intermediate between mild and severe disease
	Severe: severe diarrhea (≥6 BM/d) with macroscopic blood in stool; fever (i.e. mean evening temperature >99.5°F, or temperature >100°F for ≥2 of 4 d; tachycardia (i.e. mean pulse rate >90/min); anemia (i.e. Hb ≤75%); ESR >30 mm/h
Mayo DAI [14]	Stool frequency: 0 = normal number of daily stools; 1 = 1–2 stools/d more than normal; 2 = 3–4 stools/d more than normal; 3 = ≥5 stools/d more than normal
Minimum score: 0	Rectal bleeding: 0 = no blood; 1 = streaks of blood with stool less than half the time; 2 = obvious blood with stool most of the time; 3 = blood alone passed
Maximum score: 12	Endoscopic: 0 = normal or inactive disease; 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, no vascular pattern, friability, erosions); 3 = severe disease (spontaneous bleeding, ulceration)
	PGA: 0 = normal; 1 = mild disease; 2 = moderate disease; 3 = severe disease
UCDAI [15]	Stool frequency: 0 = normal; 1 = 1–2 stools/d more than normal; 2 = 3–4 stools/d more than normal; 3 = >4 stools/d more than normal
Minimum score: 0	Rectal bleeding: 0 = none; 1 = streaks of blood; 2 = obvious blood; 3 = mostly blood Mucosal appearance: 0 = normal; 1 = mild friability; 2 = moderate friability; 3 = exudation, spontaneous bleeding
Maximum score: 12	Physician’s rating of disease activity: 0 = normal; 1 = mild; 2 = moderate; 3 = severe
CAI by Rachmilewitz [16]	Number of weekly stools: 0 = <18; 1 = 18–35; 2 = 36–60; 3 = >60
Minimum score: 0	Blood in stool: 0 = none; 2 = little; 4 = a lot
Maximum score: 29	PGA: 0 = good; 1 = average; 2 = poor; 3 = very poor
	Abdominal pain/cramps: 0 = none; 1 = mild; 2 = moderate; 3 = severe
	Temperature (due to UC): 0 = 37–38°C; 3 = >38°C
	Extraintestinal manifestations: 3 = iritis; 3 = erythema nodosum; 3 = arthritis
	Laboratory findings: 1 = ESR >50 mm in 1st h; 2 = ESR >100 mm in 1st h; 4 = Hb <100 g/L
EI by Rachmilewitz [16]	Granulation scattering reflected light: 0 = no; 2 = yes Vascular pattern: 0 = normal; 1 = faded/disturbed; 2 = completely absent
Minimum score: 0	Mucosal vulnerability: 0 = none; 2 = slightly increased (contact bleeding); 4 = greatly increased (spontaneous bleeding)
Maximum score: 12	Mucosal damage: 0 = none; 2 = slight; 4 = pronounced
MMDAI [17]	Stool frequency: 0 = normal number of daily stools; 1 = 1–2 stools/d more than normal; 2 = 3–4 stools/d more than normal; 3 = ≥5 stools/d more than normal
Minimum score: 0	Rectal bleeding: 0 = no blood; 1 = streaks of blood with stool less than half the time; 2 = obvious blood with stool most of the time; 3 = blood alone passed
Maximum score: 12	Endoscopic: 0 = normal or inactive disease; 1 = mild disease; 2 = moderate disease (any degree of friability); 3 = severe disease
	PGA: 0 = normal; 1 = mild disease; 2 = moderate disease; 3 = severe disease

BM: bowel movement; CAI: clinical activity index; d: day(s); DAI: disease activity index; EI: endoscopic index; ESR: erythrocyte sedimentation rate; h: hour(s); Hb: hemoglobin; MMDAI: modified Mayo Disease Activity Index; PGA: physician’s global assessment; UC: ulcerative colitis; UCDAI: ulcerative colitis disease activity index.

Table 2. Clinical trials of 5-ASA in patients with mild-to-moderate UC.

Study and treatment(s)	Patient population	Definition of severity	Primary efficacy outcome(s)
Rectal 5-ASA
Sutherland et al. [15] 5-ASA 4 g/60 mL enema qhs vs. PBO	Active UP, UPS, or distal UC (≥5 cm and ≤50 cm from anus)	UCDAI ≥3	5-ASA vs. PBO: PGA ‘much improved’ from baseline at Wk 6 (63% vs. 29%; p < 0.0001)
			Decrease from baseline in UCDAI at Wk 6: 55% vs. 22% (p < 0.0001)
Campieri, et al. [36]	Active mild-to-moderate UP or UPS (≤20 cm from anus)	Truelove and Witts [13]	Remission^a at Wk 4: ○ 5-ASA 1.5 g/d, 5-ASA 1 g/d, vs. PBO: 74%, 69%, vs. 39% (p < 0.01 for 5-ASA groups vs. PBO)
5-ASA suppository 1.5 g/d, 5-ASA suppository 1 g/d, vs. PBO
Watanabe et al. [37]	Active mild-to-moderate UC with rectal inflammation	UCDAI ≥4 and ≤8 with rectal mucosal score ≥2	Endoscopic remission^b at Wk 4: ○ 5-ASA vs. PBO: 81.5% vs. 29.7% (p < 0.0001)
5-ASA 1 g suppository qd vs. PBO
Oral 5-ASA
Ito et al. [39] Oral 5-ASA pH-dependent release tablet 2.4 g/d or 3.6 g/d, vs. oral 5-ASA time-dependent release tablet 2.25 g/d, vs. PBO	Active mild-to-moderate UC	UCDAI ≥3 and ≤8 and bloody stool score ≥1 Mild UC: UCDAI ≥3 and ≤5 Moderate UC: UCDAI ≥6 and ≤8	Decrease from baseline in UCDAI at Wk 8 (primary end point): ○ 5-ASA 2.4 g, 5-ASA 3.6 g, 5-ASA 2.25 g, vs. PBO (1.5, 2.9, 1.3, vs. 0.3)
			Remission^c at Wk 8 (secondary end point): ○ 30.3%, 45.3%, 28.6%, vs. 9.4%
Flourié et al. [38] Oral 5-ASA 4 g qd vs. oral 5-ASA 2 g bid	Active mild-to-moderate UC extending beyond the rectum (≥12–18 cm from anorectal junction)	UCDAI ≥3 and ≤8	Clinical and endoscopic remission^d at Wk 8: ○ 5-ASA qd vs. 5-ASA bid: 52.1% vs. 41.8% (p = 0.1)
Oral and rectal 5-ASA
Safdi et al. [40] 5-ASA 4 g rectal enema qhs, oral 5-ASA 2.4 g/d (800 mg tablets tid), or 5-ASA 4 g enema qhs plus oral 5-ASA 2.4 g/d (combination tx)	Active mild-to-moderate distal UC (≥5 cm and ≤50 cm from anal verge)	UCDAI ≥4 and ≤10	Decrease from baseline in mean UCDAI at Wk 6: ○ 5-ASA enema, oral 5-ASA, or combination tx: 4.4, 3.9, or 5.2, respectively (p = NS for all comparisons)
Marteau et al. [41] Oral 5-ASA 1 g bid for 8 wk plus 5-ASA enema 1 g/100 mL qhs for first 4 wk (combination tx), or oral 5-ASA 1 g bid for 8 wk plus PBO enema for first 4 wk	Active extensive mild-to-moderate UC (beyond the splenic flexure by colonoscopy)	UCDAI ≥3 and ≤8 Mild UC: UCDAI ≥3 and ≤5 Moderate UC: UCDAI ≥6 and ≤8	Remission^e at Wk 4: ○ Oral 5-ASA plus 5-ASA enema vs. oral 5-ASA plus PBO enema: 44% vs. 34% (p = 0.3)

^aRemission defined as the absence of symptoms, with ≤2 BM/d without visible blood in stool.

^bEndoscopic remission defined as rectal mucosal score ≤1 at site of rectal inflammation.

^cRemission defined as UCDAI ≤2 and bloody stool subscore of 0.

^dRemission defined as UCDAI ≤1.

^eRemission defined as UCDAI <2.

5-ASA: 5-aminosalicylate; bid: twice daily; BM: bowel movement; d: day(s); NS: not significant; PBO: placebo; PGA: physician’s global assessment; qd: once daily; qhs: once daily at bedtime; tid: 3 times daily; tx: treatment; UC: ulcerative colitis; UCDAI: ulcerative colitis disease activity index; UP: ulcerative proctitis; UPS: ulcerative proctosigmoiditis; wk: week(s).

Table 3. Clinical trials with budesonide in patients with mild-to-moderate UC.

Study and treatment(s)	Patient population	Definition of severity	Primary efficacy outcome(s)
Budesonide foam
Hammond et al. [53] Budesonide foam 2 mg/50 mL vs. betamethasone enema 5 mg/100 mL bid for 2 wk, then qhs for 2 wk	Active distal UC	Pts without prior tx: CAI >8 andEI >6; Pts refractory to 5-ASA: CAI >5; Pts refractory to corticosteroid tx (prednisolone or equivalent, <20 mg for <2 wk): CAI ≥5 and EI >6	Remission^a at Wk 4: ○ Budesonide foam vs. betamethasone enema: 40.9% vs. 81.3%
Gross et al. [60] Budesonide foam 2 mg/25 mL vs. budesonide enema 2 mg/100 mL	Active UP or UPS (up to 40 cm)	CAI >4 and EI ≥4, by Rachmilewitz [16]	Remission^a at Wk 4: ○ Budesonide foam vs. budesonide enema: 65.7% vs. 59.5%
Sandborn et al. [17] Budesonide rectal foam 2 mg/25 mL vs. PBO bid for 2 wk, then qd for 4 wk	Active UP or UPS (≥5 cm and ≤40 cm from anal verge)	MMDAI ≥5 and ≤10, with subscores ≥2 for endoscopy and rectal bleeding	Remission^b at Wk 6: ○ Budesonide foam vs. PBO: 41.2% vs. 24.0% (p < 0.0001)
Naganuma et al. [64] Budesonide rectal foam 2 mg/25 mL qd or bid vs. PBO for 6 wk	Active UP or UPS (from rectum to sigmoid colon)	MMDAI subscores of 2 for endoscopy, 1 or 2 for rectal bleeding, and ≤2 for stool frequency	Complete mucosal healing at Wk 6^c: ○ Budesonide foam qd or bid vs. PBO: 23.6% or 46.6% vs. 5.6% (p = 0.0156 or p < 0.0001, respectively) Clinical remission^d: ○ Budesonide foam qd or bid vs. PBO: 50.9% or 48.2% vs. 20.4% (p = 0.0015 or p = 0.0029, respectively)
Budesonide MMX
D’Haens et al. [63] Budesonide MMX 9 mg vs. PBO	Active moderate left-sided UC (≥15 cm from anal verge to the splenic flexure)	CAI <14 [16]	Clinical improvement^e at Wk 4: ○ Budesonide MMX 9 mg vs. PBO: 47.1% vs. 33.3% (p = 0.1)
Sandborn et al. [61] Budesonide MMX 9 mg qd, budesonide MMX 6 mg qd, 5-ASA 800 mg tid, or PBO for 8 wk	Active mild-to-moderate UC	UCDAI ≥4 and ≤10, with histologic confirmation of UC performed by central reading	Combined clinical and endoscopic remission^f at Wk 8: ○ Budesonide MMX 9 mg, budesonide MMX 6 mg, 5-ASA, vs. PBO: 17.9%, 13.2%, 12.1%, vs. 7.4% (p = 0.01, p = 0.1, and p = 0.2, vs. PBO, respectively)
Travis et al. [62] Budesonide MMX 9 mg qd, budesonide MMX 6 mg qd, budesonide-CIR 9 mg/d, or PBO for 8 wk	Active mild-to-moderate UC	UCDAI ≥4 and ≤10, with histologic confirmation of UC performed by central reading	Combined clinical and endoscopic remission^f at Wk 8: ○ Budesonide MMX 9 mg, budesonide MMX 6 mg, budesonide-CIR, vs. PBO: 17.4%, 8.3%, 12.6%, vs. 4.5% (p = 0.005, p = NS, and p = 0.048, vs. PBO, respectively)

^aRemission defined as CAI ≤4.

^bRemission defined as MMDAI endoscopic subscale score ≤1, rectal bleeding subscale score = 0, and improvement or no change from baseline in stool frequency subscale score.

^cMMDAI endoscopy subscore of 0.

^dMMDAI endoscopy subscore ≤1, rectal bleeding subscore of 0, and stool frequency subscore of 0 or decrease from baseline ≥1.

^eClinical improvement defined as remission (CAI ≤4), or decrease from baseline ≥50% in CAI.

^fRemission defined as UCDAI score ≤1, with rectal bleeding and stool frequency subscores of 0, no mucosal friability on colonoscopy, and a decrease from baseline ≥1 in EI score.

5-ASA: 5-aminosalicylate; bid: twice daily; CAI: clinical activity index; CIR: controlled ileal release; EI: endoscopic index; MMDAI: modified Mayo Disease Activity Index; MMX: multi-matrix; NS: not significant; PBO: placebo; pts: patients; qd: once daily; tid: 3 times daily; tx: treatment; UC: ulcerative colitis; UCDAI: ulcerative colitis disease activity index; UP: ulcerative proctitis; UPS: ulcerative proctosigmoiditis; wk: week(s).

Table 4. Clinical trials of TNF-α antagonists in patients with moderate-to-severe UC.

		Efficacy outcomes
Study and treatment(s)	Patient population and definition of severity	Remission	Response	Mucosal healing	Rectal bleeding
Adalimumab
Induction of remission
ULTRA 1 [87] Adalimumab 160 mg SC at Wk 0, 80 mg at Wk 2, then 40 mg at Wk 4 and 6 (160/80); adalimumab 80 mg at Wk 0, then 40 mg at Wk 2, 4, and 6 (80/40); vs. PBO	Active moderate-to-severe UC Mayo score ≥6 and ≤12, with endoscopic subscale score of 2 or 3	Wk 8^a – adalimumab 160/80, 80/40, vs. PBO: 18.5%, 10%, vs. 9.2% (adalimumab 160/80 vs. PBO, p = 0.03)	Wk 8^b – adalimumab 160/80, 80/40, vs. PBO: 54.6%, 51.5%, vs. 44.6%	Wk 8^c – adalimumab 160/80, 80/40, vs. PBO: 46.9%, 37.7%, vs. 41.5%	Wk 8^d – adalimumab 160/80, 80/40, vs. PBO: 77.7%, 70%, vs. 66.2% (adalimumab 160/80 vs. PBO, p = 0.04)
ULTRA 2 [88] Adalimumab 160 mg SC at Wk 0, 80 mg at Wk 2, then 40 mg eow at Wk 4, vs. PBO for 52 wk	Moderate-to-severe UC Mayo score ≥6 and ≤12, with endoscopic subscale score of ≥2	Wk 8^a – adalimumab vs. PBO: 16.5% vs. 9.3% (p = 0.02) Wk 52^a – 17.3% vs. 8.5% (p = 0.004)	Wk 8^b – adalimumab vs. PBO: 50.4% vs. 34.6% (p < 0.001) Wk 52^b – 30.2% vs. 18.3% (p = 0.002)	Wk 8^c – adalimumab vs. PBO: 41.1% vs. 31.7% (p = 0.03) Wk 52^c – 25% vs. 15.4% (p = 0.009)	Not reported
Maintenance of remission
ULTRA 1, 2, and 3 [89] ULTRA 3: Pts receiving OL adalimumab 40 mg eow or wkly in ULTRA 1 or 2 continued same dosing; pts receiving blinded adalimumab or PBO in ULTRA 2 received adalimumab 40 mg eow	Active moderate-to-severe UC Mayo score ≥6 and ≤12, with endoscopic subscale score of ≥2, despite tx with oral corticosteroids and/or immunosuppressants (prior or current use)	Y 4^e: 24.7% Wk 52^f: 40.3% Wk 52^g: 27.4% Wk 196^g: 39.7%	Not reported	Wk 52^c: 42.3% Wk 196^c: 27.7%	Not reported
ULTRA 2 [90] Responders at Wk 8 who escalated to OL wkly dosing for 52 wk	Moderate-to-severe UC Mayo score ≥6 and ≤12, with endoscopic subscale score of ≥2	Wk 52^a – Responders: 20%, vs. nonresponders: 2.1% Wk 52^g – Responders: 17.6%, vs. nonresponders: 0%	Wk 52^b – Responders: 45%, vs. nonresponders: 25%	Wk 52^c – Responders: 45%, vs. nonresponders: 29.2%	Not reported
Golimumab
Induction of remission
PURSUIT-SC [91] Golimumab 400 mg SC at Wk 0, then 200 mg SC at Wk 2 (400/200); golimumab 200 mg SC at Wk 0, then 100 mg SC at Wk 2 (200/100); or PBO	Moderate-to-severe UC (excluding pts with UC limited to 20 cm of colon (i.e. UP)) Mayo score ≥6 and ≤12, with endoscopic subscale score ≥2	Wk 6^h – golimumab 400/200, 200/100, vs. PBO: 17.9%, 17.8%, vs. 6.4% (p < 0.0001 for both groups vs. PBO)	Wk 6^b – golimumab 400/200, 200/100, vs. PBO: 54.9%, 51.0%, vs. 30.3% (p < 0.0001 for both groups vs. PBO)	Wk 6^c – golimumab 400/200, 200/100, vs. PBO: 45.1%, 42.3%, vs. 28.7% (400/200 vs. PBO, p < 0.0001; 200/100 vs. PBO, p = 0.001)	Not reported
Maintenance of remission
PURSUIT-M [92] Golimumab 100 mg or 50 mg every 4 wk for 52 wk, or PBO	Moderate-to-severe UC Mayo score ≥6 and ≤12, with endoscopic subscale score ≥2	Wk 30 and 54^h – golimumab 100 mg, 50 mg, vs. PBO: 27.8%, 23.2%, vs. 15.6% (p = 0.004 and p = NS vs. PBO, respectively)	Wk 54^b – golimumab 100 mg, 50 mg, vs. PBO: 49.7%, 47.0%, vs. 31.2% (p < 0.001 and p = 0.01 vs. PBO, respectively)	Wk 30 and 54^c – golimumab 100 mg, 50 mg, vs. PBO: 42.4%, 41.7%, vs. 26.6% (p = 0.002 and p = 0.01 vs. PBO, respectively)	Not reported
Infliximab
Induction of remission
ACT 1 and ACT 2 [93] Infliximab 10 mg/kg or 5 mg/kg IV at Wk 0, 2, and 6, then every 8 wk for 46 wk (ACT 1) or 22 wk (ACT 2), or PBO	Active moderate-to-severe UC Mayo score ≥6 and ≤12, with endoscopic subscale score ≥2	Wk 8^a – ACT 1: infliximab 10 mg/kg, 5 mg/kg, vs. PBO: 32%, 38.8%, vs. 14.9% (p = 0.002 (10 mg/kg infliximab vs. PBO) and p = 0.001 (5 mg/kg infliximab vs. PBO)) ACT 2: 27.5%, 33.9%, vs. 5.7% (p < 0.001 for both vs. PBO)	Wk 8^b – ACT 1: infliximab 10 mg/kg, 5 mg/kg, vs. PBO: 61.5%, 69.4%, vs. 37.2% (p < 0.001 for both vs. PBO) ACT 2: 69.2%, 64.5%, vs. 29.3% (p < 0.001 for both vs. PBO)	Wk 8^c – ACT 1: infliximab 10 mg/kg, 5 mg/kg, vs. PBO: 59%, 62%, vs. 33.9% (p < 0.001 for both vs. PBO) ACT 2: 61.7%, 60.3%, vs. 30.9% (p < 0.001 for both vs. PBO)	Not reported
Infliximab
Maintenance of remission
SUCCESS [94] Infliximab 5 mg/kg IV at Wk 0, 2, 6, and 14; azathioprine 2.5 mg/kg capsules qd; or infliximab/azathioprine combination tx, for 16 wk	Active moderate-to-severe UC Moderate UC: Mayo score ≥6 and ≤8 Severe UC: Mayo score ≥9 and ≤12	Wk 16^g – infliximab, azathioprine, vs. combination tx: 22.1%, 23.7%, vs. 39.7% (infliximab vs. combination, p = 0.02; azathioprine vs. combination, p = 0.03)	Wk 16^i – infliximab, azathioprine, vs. combination tx: 68.8%, 50%, vs. 76.9% (infliximab vs. combination, p = 0.5; azathioprine vs. combination, p = 0.001)	Wk 16^c – infliximab, azathioprine, vs. combination tx: 54.6%, 36.8%, vs. 62.8% (infliximab vs. combination, p = 0.3; azathioprine vs. combination, p = 0.001)	Not reported

^aRemission defined as Mayo score ≤2, with no individual subscale score >1.

^bResponse defined as a decrease from baseline in Mayo score ≥3 and ≥30%, with either a decrease in rectal bleeding subscale score ≥1 or a rectal bleeding subscale score ≤1.

^cMucosal healing defined as Mayo endoscopic subscale score ≤1.

^dMayo rectal bleeding subscale score ≤1.

^eRemission defined as partial Mayo score ≤2, with no individual subscale score >1.

^fInflammatory Bowel Disease Questionnaire score ≥170.

^gMayo score ≤2, with no individual subscale score >1, and discontinuation of corticosteroid use.

^hRemission defined as Mayo score ≤2, with no individual subscale score >1.

ⁱResponse defined as a decrease from baseline in Mayo score ≥3 and ≥30%.

ACT 1: Active Ulcerative Colitis Trial 1; ACT 2: Active Ulcerative Colitis Trial 2; D: day(s); eow: every other week; IV: intravenous; NS: not significant; OL: open-label; PBO: placebo; pts: patients; PURSUIT-M: Program of UC Research Studies Utilizing an Investigational Treatment-Maintenance; PURSUIT-SC: Program of UC Research Studies Utilizing an Investigational Treatment-SC; qd: once daily; SC: subcutaneous; SUCCESS: trial comparing infliximab, azathioprine, or infliximab + azathioprine for treatment of moderate to severe ulcerative colitis; TNF: tumor necrosis factor; tx: treatment; UC: ulcerative colitis; ULTRA 1, 2, and 3: Ulcerative Colitis Long-Term Remission and Maintenance With Adalimumab; UP: ulcerative proctitis; wk week(s); wkly: weekly, Y: year.

Table 5. Clinical trials of vedolizumab in patients with moderate-to-severe UC.

Study and treatment(s)	Patient population and definition of severity	Efficacy outcomes
GEMINI 1 [106] Induction phase: Vedolizumab 300 mg IV vs. PBO on D 1 and 15 Maintenance phase: Vedolizumab 300 mg every 8 wk, vedolizumab every 4 wk, or PBO for up to 52 wk	Moderate-to-severe UC (extending ≥15 cm from anal verge) Mayo score ≥6 and ≤12, with endoscopic subscale score ≥2	Induction phase: Response^a at Wk 6: vedolizumab vs. PBO, 47.1% vs. 25.5% (p < 0.001) Maintenance phase: Remission^b at Wk 52: vedolizumab every 8 wk, vedolizumab every 4 wk, vs. PBO, 41.8, 44.8%, vs. 15.9% (p < 0.001 for both vs. PBO)
GEMINI LTS [105] OL tx with vedolizumab 300 mg every 4 wk^c	Moderate-to-severe UC (extending ≥15 cm from anal verge) [106] Mayo score ≥6 and ≤12, with endoscopic subscale score ≥2	Remission^d at Wk 28: 25%; and at Wk 52: 25% Response^e at Wk 28: 53.1%; and at Wk 52: 37.5%
Parikh, et al. [104] OL tx with vedolizumab 2, 6, or 10 mg/kg loading dose administered on D 1, 15, and 43; maintenance dosing every 8 wk for 18 mo	Active UC extending proximal to the rectum (confirmed by endoscopy and/or histopathology) PMS ≥2 and ≤7	Remission^d on D 43: 59% 37% of pts with PMS ≥4 at baseline achieved remission on D 43 Response^e on D 43: 31% 58% of pts with PMS ≥4 at baseline achieved response on D 43
Amiot et al. [107] Vedolizumab 300 mg IV at Wk 0, 2, and 6, and then every 8 wk, for up to 52 wk	Moderate-to-severe UC Mayo score ≥6	Clinical remission^f at Wk 14: 39% Corticosteroid-free clinical remission^f at Wk 14: 36% Clinical response^g at Wk 14: 57% Corticosteroid-free clinical response^g at Wk 14: 50%

^aResponse defined as a decrease from baseline in Mayo score ≥30% and ≥3, with either a rectal bleeding subscale score ≤1, or a decrease from baseline in rectal bleeding subscale score ≥1.

^bRemission defined as Mayo score ≤2, with no individual subscale score >1, and endoscopic subscale score ≤1 (mucosal healing).

^cResponders to vedolizumab at Wk 6 in GEMINI 1 study, but who discontinued study due to lack of response with every 8 wk dosing.

^dRemission defined as a PMS ≤2, with no individual subscale score >1.

^eResponse defined as a decrease from baseline in PMS ≥2 and ≥25%, with either a decrease from baseline in rectal bleeding subscale score ≥1 or a rectal bleeding subscale score ≤1.

^fRemission defined as PMS <3 with combined subscores for stool frequency and rectal bleeding ≤1.

^gResponse defined as decrease from baseline in PMS ≥3 and ≥30%, with either a decrease from baseline in rectal bleeding subscale score ≥1 or an absolute rectal bleeding subscale score ≤1.

D: day(s); GEMINI 1: study of vedolizumab in patients with moderate to severe UC; GEMINI LTS: OL study of vedolizumab in patients with UC and Crohn’s disease; IV: intravenous; LTS: long-term extension study; mo: month(s); OL: open-label; PBO: placebo; PMS: partial Mayo score; pts: patients; tx: treatment; UC: ulcerative colitis; wk: week(s).

Figure 1. Treat-to-target recommendations for UC from the International Organization for the Study of Inflammatory Bowel Diseases.

CRP: C-reactive protein, UC: ulcerative colitisData from Peyrin-Biroulet, et al. Am J Gastroenterol. 2015;110:1329 [139].

Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955;2:1041–1048.

 PubMed Web of Science ®Google Scholar

Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. a randomized study. N Engl J Med. 1987;317:1625–1629.

 PubMed Web of Science ®Google Scholar

Sutherland LR, Martin F, Greer S, et al. 5-aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. Gastroenterology. 1987;92:1894–1898.

 PubMed Web of Science ®Google Scholar

Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. BMJ. 1989;298:82–86.

 PubMed Web of Science ®Google Scholar

Sandborn WJ, Bosworth B, Zakko S, et al. Budesonide foam induces remission in patients with mild-moderate ulcerative proctitis and ulcerative proctosigmoiditis. Gastroenterology. 2015;148:740–750.e2.

 PubMed Web of Science ®Google Scholar

Campieri M, De Franchis R, Bianchi Porro G, et al. Mesalazine (5-aminosalicylic acid) suppositories in the treatment of ulcerative proctitis or distal proctosigmoiditis. A randomized controlled trial. Scand J Gastroenterol. 1990;25:663–668.

 PubMed Web of Science ®Google Scholar

Watanabe M, Nishino H, Sameshima Y, et al. Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppos-itories in patients with ulcerative colitis and active rectal inflammation – a placebo-controlled study. Aliment Pharmacol Ther. 2013;38:264–273.

 PubMed Web of Science ®Google Scholar

Ito H, Iida M, Matsumoto T, et al. Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: a double-blind, randomized study. Inflamm Bowel Dis. 2010;16:1567–1574.

 PubMed Web of Science ®Google Scholar

Flourié B, Hagege H, Tucat G, et al. Randomised clinical trial: once- vs. twice-daily prolonged-release mesalazine for active ulcerative colitis. Aliment Pharmacol Ther. 2013;37:767–775.

 PubMed Web of Science ®Google Scholar

Safdi M, DeMicco M, Sninsky C, et al. A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis. Am J Gastroenterol. 1997;92:1867–1871.

 PubMed Web of Science ®Google Scholar

Marteau P, Probert CS, Lindgren S, et al. Combined oral and enema treatment with Pentasa (mesalazine) is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised, double blind, placebo controlled study. Gut. 2005;54:960–965.

 PubMed Web of Science ®Google Scholar

Hammond A, Andus T, Gierend M, et al. Controlled, open, randomized multicenter trial comparing the effects of treatment on quality of life, safety and efficacy of budesonide foam and betamethasone enemas in patients with active distal ulcerative colitis. Hepatogastroenterology. 2004;51:1345–1349.

 PubMed Web of Science ®Google Scholar

Gross V, Bar-Meir S, Lavy A, et al. Budesonide foam versus budesonide enema in active ulcerative proctitis and proctosigmoiditis. Aliment Pharmacol Ther. 2006;23:303–312.

 PubMed Web of Science ®Google Scholar

Naganuma M, Aoyama N, Suzuki Y, et al. Twice-daily budesonide 2-mg foam induces complete mucosal healing in patients with distal ulcerative colitis. J Crohns Colitis. 2016;10:828–836.

 PubMed Web of Science ®Google Scholar

D’Haens GR, Kovács A, Vergauwe P, et al. Clinical trial: preliminary efficacy and safety study of a new budesonide-MMX® 9 mg extended-release tablets in patients with active left-sided ulcerative colitis. J Crohns Colitis. 2010;4:153–160.

 PubMed Web of Science ®Google Scholar

Sandborn WJ, Travis S, Moro L, et al. Once-daily budesonide MMX® extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. Gastroenterology. 2012;143:1218–1226.

 PubMed Web of Science ®Google Scholar

Travis SP, Danese S, Kupcinskas L, et al. Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study. Gut. 2014;63:433–441.

 PubMed Web of Science ®Google Scholar

Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011;60:780–787.

 PubMed Web of Science ®Google Scholar

Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142:257–265.

 PubMed Web of Science ®Google Scholar

Colombel JF, Sandborn WJ, Ghosh S, et al. Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: data from ULTRA 1, 2, and 3. Am J Gastroenterol. 2014;109:1771–1780.

 PubMed Web of Science ®Google Scholar

Wolf D, D’Haens G, Sandborn WJ, et al. Escalation to weekly dosing recaptures response in adalimumab-treated patients with moderately to severely active ulcerative colitis. Aliment Pharmacol Ther. 2014;40:486–497.

 PubMed Web of Science ®Google Scholar

Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:85–95.

 PubMed Web of Science ®Google Scholar

Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:96–109.

 PubMed Web of Science ®Google Scholar

Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–2476.

 PubMed Web of Science ®Google Scholar

Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014;146:392–400.

 PubMed Web of Science ®Google Scholar

Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710.

 PubMed Web of Science ®Google Scholar

Sands B, Dubinsky S, Vermeire S, et al. Effects of increased vedolizumab dosing frequency on clinical remission and response in ulcerative colitis and Crohn’s disease [Abstract P-098]. Inflamm Bowel Dis. 2014;20:S67.

 Google Scholar

Parikh A, Fox I, Leach T, et al. Long-term clinical experience with vedolizumab in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19:1691–1699.

 PubMed Web of Science ®Google Scholar

Amiot A, Grimaud JC, Peyrin-Biroulet L, et al. Effectiveness and safety of vedolizumab induction therapy for patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2016;14:1593–1601 e2.

 PubMed Web of Science ®Google Scholar

Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110:1324–1338.

 PubMed Web of Science ®Google Scholar