14 CLINICAL STUDIES

14.1 Adult Plaque Psoriasis

Two multicenter, randomized, double-blind, placebo-controlled trials (Ps STUDY 1 and Ps STUDY 2) enrolled a total of 1996 subjects 18 years of age and older with plaque psoriasis who had a minimum body surface area involvement of 10%, and Psoriasis Area and Severity Index (PASI) score ≥12, and who were candidates for phototherapy or systemic therapy. Subjects with guttate, erythrodermic, or pustular psoriasis were excluded from the trials.

Ps STUDY 1 enrolled 766 subjects and Ps STUDY 2 enrolled 1230 subjects. The trials had the same design through Week 28. In both trials, subjects were randomized in equal proportion to placebo, 45 mg or 90 mg of STELARA ®. Subjects randomized to STELARA ® received 45 mg or 90 mg doses, regardless of weight, at Weeks 0, 4, and 16. Subjects randomized to receive placebo at Weeks 0 and 4 crossed over to receive STELARA ® (either 45 mg or 90 mg) at Weeks 12 and 16.

In both trials, subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline PGA score was marked or severe in 44% of subjects in Ps STUDY 1 and 40% of subjects in Ps STUDY 2. Approximately two-thirds of all subjects had received prior phototherapy, 69% had received either prior conventional systemic or biologic therapy for the treatment of psoriasis, with 56% receiving prior conventional systemic therapy and 43% receiving prior biologic therapy. A total of 28% of subjects had a history of psoriatic arthritis.

In both trials, the endpoints were the proportion of subjects who achieved at least a 75% reduction in PASI score (PASI 75) from baseline to Week 12 and treatment success (cleared or minimal) on the Physician's Global Assessment (PGA). The PGA is a 6-category scale ranging from 0 (cleared) to 5 (severe) that indicates the physician's overall assessment of psoriasis focusing on plaque thickness/induration, erythema, and scaling.

Clinical Response

The results of Ps STUDY 1 and Ps STUDY 2 are presented in Table 8 below.

Table 8: Clinical Outcomes at Week 12 in Adults with Plaque Psoriasis in Ps STUDY 1 and Ps STUDY 2
	Ps STUDY 1			Ps STUDY 2
		STELARA ®			STELARA ®
	Placebo	45 mg	90 mg	Placebo	45 mg	90 mg
Subjects randomized	255	255	256	410	409	411
PASI 75 response	8 (3%)	171 (67%)	170 (66%)	15 (4%)	273 (67%)	311 (76%)
PGA of Cleared or Minimal	10 (4%)	151 (59%)	156 (61%)	18 (4%)	277 (68%)	300 (73%)

Examination of age, gender, and race subgroups did not identify differences in response to STELARA ®among these subgroups.

In subjects who weighed 100 kg or less, response rates were comparable with both the 45 mg and 90 mg doses; however, in subjects who weighed greater than 100 kg, higher response rates were seen with 90 mg dosing compared with 45 mg dosing (Table 9 below).

Table 9: Clinical Outcomes by Weight at Week 12 in Adults with Plaque Psoriasis in Ps STUDY 1 and Ps STUDY 2
	Ps STUDY 1			Ps STUDY 2
		STELARA ®			STELARA ®
	Placebo	45 mg	90 mg	Placebo	45 mg	90 mg
* Subjects were dosed with trial medication at Weeks 0 and 4.
Subjects randomized	255	255	256	410	409	411
PASI 75 response *
≤100 kg	4%	74%	65%	4%	73%	78%
	6/166	124/168	107/164	12/290	218/297	225/289
>100 kg	2%	54%	68%	3%	49%	71%
	2/89	47/87	63/92	3/120	55/112	86/121
PGA of Cleared or Minimal *
≤100 kg	4%	64%	63%	5%	74%	75%
	7/166	108/168	103/164	14/290	220/297	216/289
>100 kg	3%	49%	58%	3%	51%	69%
	3/89	43/87	53/92	4/120	57/112	84/121

Subjects in Ps STUDY 1 who were PASI 75 responders at both Weeks 28 and 40 were re-randomized at Week 40 to either continued dosing of STELARA ®(STELARA ®at Week 40) or to withdrawal of therapy (placebo at Week 40). At Week 52, 89% (144/162) of subjects re-randomized to STELARA ®treatment were PASI 75 responders compared with 63% (100/159) of subjects re-randomized to placebo (treatment withdrawal after Week 28 dose). The median time to loss of PASI 75 response among the subjects randomized to treatment withdrawal was 16 weeks.

14.2 Pediatric Plaque Psoriasis

A multicenter, randomized, double blind, placebo-controlled trial (Ps STUDY 3) enrolled 110 pediatric subjects 12 to 17 years of age with a minimum BSA involvement of 10%, a PASI score greater than or equal to 12, and a PGA score greater than or equal to 3, who were candidates for phototherapy or systemic therapy and whose disease was inadequately controlled by topical therapy.

Subjects were randomized to receive placebo (n = 37), the recommended dose of STELARA ®(n = 36), or one-half the recommended dose of STELARA ®(n = 37) by subcutaneous injection at Weeks 0 and 4 followed by dosing every 12 weeks (q12w). The recommended dose of STELARA ®was 0.75 mg/kg for subjects weighing less than 60 kg, 45 mg for subjects weighing 60 kg to 100 kg, and 90 mg for subjects weighing greater than 100 kg. At Week 12, subjects who received placebo were crossed over to receive STELARA ®at the recommended dose or one-half the recommended dose.

Of the pediatric subjects, approximately 63% had prior exposure to phototherapy or conventional systemic therapy and approximately 11% had prior exposure to biologics.

The endpoints were the proportion of subjects who achieved a PGA score of cleared (0) or minimal (1), PASI 75, and PASI 90 at Week 12. Subjects were followed for up to 60 weeks following first administration of trial agent.

Clinical Response

The efficacy results at Week 12 for Ps STUDY 3 are presented in Table 10.

Table 10: Efficacy Results at Week 12 in Pediatric Subjects 12 to 17 years with Plaque Psoriasis in Ps STUDY 3
	Ps STUDY 3
	Placebo n (%)	STELARA ®* n (%)
* Using the weight-based dosage regimen specified in Table 1 and Table 2.
N	37	36
PGA
PGA of cleared (0) or minimal (1)	2 (5.4%)	25 (69.4%)
PASI
PASI 75 responders	4 (10.8%)	29 (80.6%)
PASI 90 responders	2 (5.4%)	22 (61.1%)

14.3 Psoriatic Arthritis

The safety and efficacy of STELARA ®was assessed in 927 subjects (PsA STUDY 1, n=615; PsA STUDY 2, n=312), in two randomized, double-blind, placebo-controlled trials in adult subjects 18 years of age and older with active PsA (≥5 swollen joints and ≥5 tender joints) despite nonsteroidal anti-inflammatory (NSAID) or disease modifying antirheumatic (DMARD) therapy. Subjects in these trials had a diagnosis of PsA for at least 6 months. Subjects with each subtype of PsA were enrolled, including polyarticular arthritis with the absence of rheumatoid nodules (39%), spondylitis with peripheral arthritis (28%), asymmetric peripheral arthritis (21%), distal interphalangeal involvement (12%) and arthritis mutilans (0.5%). Over 70% and 40% of the patients, respectively, had enthesitis and dactylitis at baseline.

Subjects were randomized to receive treatment with STELARA ®45 mg, 90 mg, or placebo subcutaneously at Weeks 0 and 4 followed by every 12 weeks (q12w) dosing. Approximately 50% of subjects continued on stable doses of MTX (≤25 mg/week). The primary endpoint was the percentage of subjects achieving ACR 20 response at Week 24.

In PsA STUDY 1 and PsA STUDY 2, 80% and 86% of the subjects, respectively, had been previously treated with DMARDs. In PsA STUDY 1, previous treatment with anti-tumor necrosis factor (TNF)-α agent was not allowed. In PsA STUDY 2, 58% (n=180) of the subjects had been previously treated with TNF blocker, of whom over 70% had discontinued their TNF blocker treatment for lack of efficacy or intolerance at any time.

Clinical Response

In both trials, a greater proportion of subjects achieved ACR 20, ACR 50 and PASI 75 response in the STELARA ®45 mg and 90 mg groups compared to placebo at Week 24 (see Table 11). ACR 70 responses were also higher in the STELARA ®45 mg and 90 mg groups, although the difference was only numerical (p=NS) in STUDY 2. Responses were consistent in subjects treated with STELARA ®alone or in combination with methotrexate. Responses were similar in subjects regardless of prior TNFα exposure.

Table 11: ACR 20, ACR 50, ACR 70 and PASI 75 responses in PsA STUDY 1 and PsA STUDY 2 at Week 24
	PsA STUDY 1			PsA STUDY 2
		STELARA ®			STELARA ®
	Placebo	45 mg	90 mg	Placebo	45 mg	90 mg
* Number of subjects with ≥ 3% BSA psoriasis skin involvement at baseline
Number of subjects randomized	206	205	204	104	103	105
ACR 20 response, N (%)	47 (23%)	87 (42%)	101 (50%)	21 (20%)	45 (44%)	46 (44%)
ACR 50 response, N (%)	18 (9%)	51 (25%)	57 (28%)	7 (7%)	18 (17%)	24 (23%)
ACR 70 response, N (%)	5 (2%)	25 (12%)	29 (14%)	3 (3%)	7 (7%)	9 (9%)
Number of subjects with ≥ 3% BSA *	146	145	149	80	80	81
PASI 75 response, N (%)	16 (11%)	83 (57%)	93 (62%)	4 (5%)	41 (51%)	45 (56%)

The percent of subjects achieving ACR 20 responses by visit is shown in Figure 1.

Figure 1: Percent of subjects achieving ACR 20 response through Week 24
PsA STUDY 1

The results of the components of the ACR response criteria are shown in Table 12.

Table 12: Mean change from baseline in ACR components at Week 24
	PsA STUDY 1
		STELARA ®
	Placebo (N = 206)	45 mg (N = 205)	90 mg (N = 204)
* Number of swollen joints counted (0–66) † Number of tender joints counted (0–68) ‡ Visual analogue scale; 0= best, 10=worst. § Disability Index of the Health Assessment Questionnaire; 0 = best, 3 = worst, measures the patient's ability to perform the following: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity. ¶ CRP: (Normal Range 0.0–1.0 mg/dL)
Number of swollen joints *
Baseline	15	12	13
Mean Change at Week 24	-3	-5	-6
Number of tender joints †
Baseline	25	22	23
Mean Change at Week 24	-4	-8	-9
Subject's assessment of pain ‡
Baseline	6.1	6.2	6.6
Mean Change at Week 24	-0.5	-2.0	-2.6
Subject global assessment ‡
Baseline	6.1	6.3	6.4
Mean Change at Week 24	-0.5	-2.0	-2.5
Physician global assessment ‡
Baseline	5.8	5.7	6.1
Mean Change at Week 24	-1.4	-2.6	-3.1
Disability index (HAQ) §
Baseline	1.2	1.2	1.2
Mean Change at Week 24	-0.1	-0.3	-0.4
CRP (mg/dL) ¶
Baseline	1.6	1.7	1.8
Mean Change at Week 24	0.01	-0.5	-0.8

An improvement in enthesitis and dactylitis scores was observed in each STELARA ®group compared with placebo at Week 24.

Physical Function

STELARA ®-treated subjects showed improvement in physical function compared to subjects treated with placebo as assessed by HAQ-DI at Week 24. In both trials, the proportion of HAQ-DI responders (≥0.3 improvement in HAQ-DI score) was greater in the STELARA ®45 mg and 90 mg groups compared to placebo at Week 24.

14.4 Crohn's Disease

STELARA ®was evaluated in three randomized, double-blind, placebo-controlled clinical trials in adult subjects with moderately to severely active Crohn's disease (Crohn's Disease Activity Index [CDAI] score of 220 to 450). There were two 8-week intravenous induction trials(CD-1 and CD-2) followed by a 44-week subcutaneous randomized withdrawal maintenance trial (CD-3) representing 52 weeks of therapy. Subjects in CD-1 had failed or were intolerant to treatment with one or more TNF blockers, while subjects in CD-2 had failed or were intolerant to treatment with immunomodulators or corticosteroids, but never failed treatment with a TNF blocker.

Trials CD-1 and CD-2

In trials CD-1 and CD-2, 1409 subjects were randomized, of whom 1368 (CD-1, n=741; CD-2, n=627) were included in the final efficacy analysis. Induction of clinical response (defined as a reduction in CDAI score of greater than or equal to 100 points or CDAI score of less than 150) at Week 6 and clinical remission (defined as a CDAI score of less than 150) at Week 8 were evaluated. In both trials, subjects were randomized to receive a single intravenous administration of STELARA ®at either approximately 6 mg/kg, placebo (see Table 4), or 130 mg (a lower dose than recommended).

In trial CD-1, subjects had failed or were intolerant to prior treatment with a TNF blocker: 29% subjects had an inadequate initial response (primary non-responders), 69% responded but subsequently lost response (secondary non-responders) and 36% were intolerant to a TNF blocker. Of these subjects, 48% failed or were intolerant to one TNF blocker and 52% had failed 2 or 3 prior TNF blockers. At baseline and throughout the trial, approximately 46% of the subjects were receiving corticosteroids and 31% of the subjects were receiving immunomodulators (AZA, 6-MP, MTX). The median baseline CDAI score was 319 in the STELARA ®approximately 6 mg/kg group and 313 in the placebo group.

In trial CD-2, subjects had failed or were intolerant to prior treatment with corticosteroids (81% of subjects), at least one immunomodulator (6-MP, AZA, MTX; 68% of subjects), or both (49% of subjects). Additionally, 69% never received a TNF blocker and 31% previously received but had not failed a TNF blocker. At baseline, and throughout the trial, approximately 39% of the subjects were receiving corticosteroids and 35% of the subjects were receiving immunomodulators (AZA, 6-MP, MTX). The median baseline CDAI score was 286 in the STELARA ®and 290 in the placebo group.

In these induction trials, a greater proportion of subjects treated with STELARA ®(at the recommended dose of approximately 6 mg/kg dose) achieved clinical response at Week 6 and clinical remission at Week 8 compared to placebo (see Table 13 for clinical response and remission rates). Clinical response and remission were significant as early as Week 3 in STELARA ®-treated subjects and continued to improve through Week 8.

Table 13: Induction of Clinical Response and Remission in CD-1 *and CD-2 †
	CD-1 n = 741			CD-2 n = 627
	Placebo N = 247	STELARA ®‡ N = 249	Treatment difference and 95% CI	Placebo N = 209	STELARA ®‡ N = 209	Treatment difference and 95% CI
Clinical remission is defined as CDAI score < 150; Clinical response is defined as reduction in CDAI score by at least 100 points or being in clinical remission: 70 point response is defined as reduction in CDAI score by at least 70 points
* Patient population consisted of subjects who failed or were intolerant to TNF blocker therapy † Patient population consisted of subjects who failed or were intolerant to corticosteroids or immunomodulators (e.g., 6-MP, AZA, MTX) and previously received but not failed a TNF blocker or were never treated with a TNF blocker. ‡ Infusion dose of STELARA ® using the weight-based dosage regimen specified in Table 4. § 0.001≤ p < 0.01 ¶ p < 0.001
Clinical Response (100 point), Week 6	53 (21%)	84 (34%) §	12% (4%, 20%)	60 (29%)	116 (56%) ¶	27% (18%, 36%)
Clinical Remission, Week 8	18 (7%)	52 (21%) ¶	14% (8%, 20%)	41 (20%)	84 (40%) ¶	21% (12%, 29%)
Clinical Response (100 point), Week 8	50 (20%)	94 (38%) ¶	18% (10%, 25%)	67 (32%)	121 (58%) ¶	26% (17%, 35%)
70 Point Response, Week 6	75 (30%)	109 (44%) §	13% (5%, 22%)	81 (39%)	135 (65%) ¶	26% (17%, 35%)
70 Point Response, Week 3	67 (27%)	101 (41%) §	13% (5%, 22%)	66 (32%)	106 (51%) ¶	19% (10%, 28%)

Trial CD-3

The maintenance trial (CD-3), evaluated 388 subjects who achieved clinical response (≥100 point reduction in CDAI score) at Week 8 with either induction dose of STELARA ®in trials CD-1 or CD-2. Subjects were randomized to receive a subcutaneous maintenance regimen of either 90 mg STELARA ®every 8 weeks or placebo for 44 weeks (see Table 14).

Table 14: Clinical Response and Remission in CD-3 (Week 44; 52 weeks from initiation of the induction dose)
	Placebo *	90 mg STELARA ®every 8 weeks	Treatment difference and 95% CI
	N = 131 †	N = 128 †	Treatment difference and 95% CI
Clinical remission is defined as CDAI score < 150; Clinical response is defined as reduction in CDAI of at least 100 points or being in clinical remission
* The placebo group consisted of subjects who were in response to STELARA ® and were randomized to receive placebo at the start of maintenance therapy. † Subjects who achieved clinical response to STELARA ® at the end of the induction trial. ‡ p < 0.01 § 0.01≤ p < 0.05 ¶ Subjects in remission at the end of maintenance therapy who were in remission at the start of maintenance therapy. This does not account for any other time point during maintenance therapy.
Clinical Remission	47 (36%)	68 (53%) ‡	17% (5%, 29%)
Clinical Response	58 (44%)	76 (59%) §	15% (3%, 27%)
Clinical Remission in patients in remission at the start of maintenance therapy ¶	36/79 (46%)	52/78 (67%) ‡	21% (6%, 36%)

At Week 44, 47% of subjects who received STELARA ®were corticosteroid-free and in clinical remission, compared to 30% of subjects in the placebo group.

At Week 0 of trial CD-3, 34/56 (61%) STELARA ®-treated subjects who previously failed or were intolerant to TNF blocker therapies were in clinical remission and 23/56 (41%) of these subjects were in clinical remission at Week 44. In the placebo arm, 27/61 (44%) subjects were in clinical remission at Week 0 while 16/61 (26%) of these subjects were in remission at Week 44.

At Week 0 of trial CD-3, 46/72 (64%) STELARA ®-treated subjects who had previously failed immunomodulator therapy or corticosteroids (but not TNF blockers) were in clinical remission and 45/72 (63%) of these subjects were in clinical remission at Week 44. In the placebo arm, 50/70 (71%) of these subjects were in clinical remission at Week 0 while 31/70 (44%) were in remission at Week 44. In the subset of these subjects who were also naïve to TNF blockers, 34/52 (65%) of STELARA ®-treated subjects were in clinical remission at Week 44 as compared to 25/51 (49%) in the placebo arm.

Subjects who were not in clinical response 8 weeks after STELARA ®induction were not included in the primary efficacy analyses for trial CD-3; however, these subjects were eligible to receive a 90 mg subcutaneous injection of STELARA ®upon entry into trial CD-3. Of these subjects, 102/219 (47%) achieved clinical response eight weeks later and were followed for the duration of the trial.

14.5 Ulcerative Colitis

STELARA ®was evaluated in two randomized, double-blind, placebo-controlled clinical trials [UC-1 and UC-2 (NCT02407236)] in adult subjects with moderately to severely active ulcerative colitis who had an inadequate response to or failed to tolerate a biologic (i.e., TNF blocker and/or vedolizumab), corticosteroids, and/or 6-MP or AZA therapy. The 8-week intravenous induction trial (UC-1) was followed by the 44-week subcutaneous randomized withdrawal maintenance trial (UC-2) for a total of 52 weeks of therapy.

Disease assessment was based on the Mayo score, which ranged from 0 to 12 and has four subscores that were each scored from 0 (normal) to 3 (most severe): stool frequency, rectal bleeding, findings on centrally-reviewed endoscopy, and physician global assessment. Moderately to severely active ulcerative colitis was defined at baseline (Week 0) as Mayo score of 6 to 12, including a Mayo endoscopy subscore ≥2. An endoscopy score of 2 was defined by marked erythema, absent vascular pattern, friability, erosions; and a score of 3 was defined by spontaneous bleeding, ulceration. At baseline, subjects had a median Mayo score of 9, with 84% of subjects having moderate disease (Mayo score 6–10) and 15% having severe disease (Mayo score 11–12).

Subjects in these trials may have received other concomitant therapies including aminosalicylates, immunomodulatory agents (AZA, 6-MP, or MTX), and oral corticosteroids (prednisone).

Trial UC-1

In UC-1, 961 subjects were randomized at Week 0 to a single intravenous administration of STELARA ®of approximately 6 mg/kg, 130 mg (a lower dose than recommended), or placebo. Subjects enrolled in UC-1 had to have failed therapy with corticosteroids, immunomodulators or at least one biologic. A total of 51% had failed at least one biologic and 17% had failed both a TNF blocker and an integrin receptor blocker. Of the total population, 46% had failed corticosteroids or immunomodulators but were biologic-naïve and an additional 3% had previously received but had not failed a biologic. At induction baseline and throughout the trial, approximately 52% subjects were receiving oral corticosteroids, 28% subjects were receiving immunomodulators (AZA, 6-MP, or MTX) and 69% subjects were receiving aminosalicylates.

The primary endpoint was clinical remission at Week 8. Clinical remission with a definition of: Mayo stool frequency subscore of 0 or 1, Mayo rectal bleeding subscore of 0 (no rectal bleeding), and Mayo endoscopy subscore of 0 or 1 (Mayo endoscopy subscore of 0 defined as normal or inactive disease and Mayo subscore of 1 defined as presence of erythema, decreased vascular pattern and no friability) is provided in Table 15.

The secondary endpoints were clinical response, endoscopic improvement, and histologic-endoscopic mucosal improvement. Clinical response with a definition of (≥ 2 points and ≥ 30% decrease in modified Mayo score, defined as 3-component Mayo score without the Physician's Global Assessment, with either a decrease from baseline in the rectal bleeding subscore ≥1 or a rectal bleeding subscore of 0 or 1), endoscopic improvement with a definition of Mayo endoscopy subscore of 0 or 1, and histologic-endoscopic mucosal improvement with a definition of combined endoscopic improvement and histologic improvement of the colon tissue [neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue]) are provided in Table 15.

In UC-1, a significantly greater proportion of subjects treated with STELARA ®(at the recommended dose of approximately 6 mg/kg dose) were in clinical remission and response and achieved endoscopic improvement and histologic-endoscopic mucosal improvement compared to placebo (see Table 15).

Table 15: Proportion of Subjects Meeting Efficacy Endpoints at Week 8 in UC-1
Endpoint	Placebo N = 319		STELARA ®* N = 322		Treatment difference and 97.5% CI †
Endpoint	N	%	N	%	Treatment difference and 97.5% CI †
* Infusion dose of STELARA ® using the weight-based dosage regimen specified in Table 4. † Adjusted treatment difference (97.5% CI) ‡ Clinical remission was defined as Mayo stool frequency subscore of 0 or 1, Mayo rectal bleeding subscore of 0, and Mayo endoscopy subscore of 0 or 1 (modified so that 1 does not include friability). § p < 0.001 ¶ An additional 7 subjects on placebo and 9 subjects on STELARA ® (6 mg/kg) had been exposed to, but had not failed, biologics. # Endoscopic improvement was defined as Mayo endoscopy subscore of 0 or 1 (modified so that 1 does not include friability). Þ Clinical response was defined as a decrease from baseline in the modified Mayo score by ≥30% and ≥2 points, with either a decrease from baseline in the rectal bleeding subscore ≥1 or a rectal bleeding subscore of 0 or 1. ß Histologic-endoscopic mucosal improvement was defined as combined endoscopic improvement (Mayo endoscopy subscore of 0 or 1) and histologic improvement of the colon tissue (neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue).
Clinical Remission ‡	22	7%	62	19%	12% (7%, 18%) §
Bio-naïve ¶	14/151	9%	36/147	24%
Prior biologic failure	7/161	4%	24/166	14%
Endoscopic Improvement #	40	13%	80	25%	12% (6%, 19%) §
Bio-naïve ¶	28/151	19%	43/147	29%
Prior biologic failure	11/161	7%	34/166	20%
Clinical Response Þ	99	31%	186	58%	27% (18%, 35%) §
Bio-naïve ¶	55/151	36%	94/147	64%
Prior biologic failure	42/161	26%	86/166	52%
Histologic-Endoscopic Mucosal Improvement ß	26	8%	54	17%	9% (3%, 14%) §
Bio-naïve ¶	19/151	13%	30/147	20%
Prior biologic failure	6/161	4%	21/166	13%

The relationship of histologic-endoscopic mucosal improvement, as defined in UC-1, at Week 8 to disease progression and long-term outcomes was not evaluated during UC-1.

Rectal Bleeding and Stool Frequency Subscores

Decreases in rectal bleeding and stool frequency subscores were observed as early as Week 2 in STELARA ®-treated subjects.

Trial UC-2

The maintenance trial (UC-2) evaluated 523 subjects who achieved clinical response 8 weeks following the intravenous administration of either induction dose of STELARA ®in UC-1. These subjects were randomized to receive a subcutaneous maintenance regimen of either 90 mg STELARA ®every 8 weeks, or every 12 weeks (a lower dose than recommended), or placebo for 44 weeks.

The primary endpoint was the proportion of subjects in clinical remission at Week 44. The secondary endpoints included the proportion of subjects maintaining clinical response at Week 44, the proportion of subjects with endoscopic improvement at Week 44, the proportion of subjects with corticosteroid-free clinical remission at Week 44, and the proportion of subjects maintaining clinical remission at Week 44 among subjects who achieved clinical remission 8 weeks after induction.

Results of the primary and secondary endpoints at Week 44 in subjects treated with STELARA ®at the recommended dosage (90 mg every 8 weeks) compared to the placebo are shown in Table 16.

Table 16: Efficacy Endpoints of Maintenance at Week 44 in UC-2 (52 Weeks from Initiation of the Induction Dose)
Endpoint	Placebo * N = 175 †		90 mg STELARA ®every 8 weeks N = 176		Treatment difference and 95% CI
Endpoint	N	%	N	%	Treatment difference and 95% CI
* The placebo group consisted of subjects who were in response to STELARA ® and were randomized to receive placebo at the start of maintenance therapy. † Clinical response was defined as a decrease from baseline in the modified Mayo score by ≥30% and ≥2 points, with either a decrease from baseline in the rectal bleeding subscore ≥1 or a rectal bleeding subscore of 0 or 1. ‡ Clinical remission was defined as Mayo stool frequency subscore of 0 or 1, Mayo rectal bleeding subscore of 0, and Mayo endoscopy subscore of 0 or 1 (modified so that 1 does not include friability). § p =<0.001 ¶ An additional 3 subjects on placebo and 6 subjects on STELARA ® had been exposed to, but had not failed, biologics. # Endoscopic improvement was defined as Mayo endoscopy subscore of 0 or 1 (modified so that 1 does not include friability). Þ Corticosteroid-free clinical remission was defined as subjects in clinical remission and not receiving corticosteroids at Week 44. ß p=0.004
Clinical Remission ‡	46	26%	79	45%	19% (9%, 28%) §
Bio-naïve ¶	30/84	36%	39/79	49%
Prior biologic failure	16/88	18%	37/91	41%
Maintenance of Clinical Response at Week 44 †	84	48%	130	74%	26% (16%, 36%) §
Bio-naïve ¶	49/84	58%	62/79	78%
Prior biologic failure	35/88	40%	64/91	70%
Endoscopic Improvement #	47	27%	83	47%	20% (11%, 30%) §
Bio-naïve ¶	29/84	35%	42/79	53%
Prior biologic failure	18/88	20%	38/91	42%
Corticosteroid-free Clinical Remission Þ	45	26%	76	43%	17% (8%, 27%) §
Bio-naïve ¶	30/84	36%	38/79	48%
Prior biologic failure	15/88	17%	35/91	38%
Maintenance of Clinical Remission at Week 44 in subjects who achieved clinical remission 8 weeks after induction	18/50	36%	27/41	66%	31% (12%, 50%) ß
Bio-naïve ¶	12/27	44%	14/20	70%
Prior biologic failure	6/23	26%	12/18	67%

Other Endpoints

Week 16 Responders to Ustekinumab Induction

Subjects who were not in clinical response 8 weeks after induction with STELARA ®in UC-1 were not included in the primary efficacy analyses for trial UC-2; however, these subjects were eligible to receive a 90 mg subcutaneous injection of STELARA ®at Week 8. Of these subjects, 55/101 (54%) achieved clinical response eight weeks later (Week 16) and received STELARA ®90 mg subcutaneously every 8 weeks during the UC-2 trial. At Week 44, there were 97/157 (62%) subjects who maintained clinical response and there were 51/157 (32%) who achieved clinical remission.

Histologic-Endoscopic Mucosal Improvement at Week 44

The proportion of subjects achieving histologic-endoscopic mucosal improvement during maintenance treatment in UC-2 was 75/172 (44%) among subjects on STELARA ®and 40/172 (23%) in subjects on placebo at Week 44. The relationship of histologic-endoscopic mucosal improvement, as defined in UC-2, at Week 44 to progression of disease or long-term outcomes was not evaluated in UC-2.

Endoscopic Normalization

Normalization of endoscopic appearance of the mucosa was defined as a Mayo endoscopic subscore of 0. At Week 8 in UC-1, endoscopic normalization was achieved in 25/322 (8%) of subjects treated with STELARA ®and 12/319 (4%) of subjects in the placebo group. At Week 44 of UC-2, endoscopic normalization was achieved in 51/176 (29%) of subjects treated with STELARA ®and in 32/175 (18%) of subjects in placebo group.