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STELARA® (ustekinumab)

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Re-induce with Intravenous Infusion of STELARA During Maintenance Therapy in Crohn’s Disease

Last Updated: 03/23/2025

Click on the following links to related sections within the document:, Phase 3b Study: POWER, Phase 3 Study: REScUE Study, and Retrospective Studies.
Abbreviations: AE, adverse event; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; CI, confidence interval; CRP, C-reactive protein; FCP, fecal calprotectin; IV, intravenous; LoR, loss of response; q8w, every 8 weeks; R, randomization; SAE, serious adverse event; SC, subcutaneous; SOC, standard of care; UST, ustekinumab.
^aSchreiber (2023)¹. ^bSecondary LoR was defined as a CDAI score of ≥220 and ≤450 and at least 1 objective sign of inflammation: elevated CRP (>3 mg/L) or FCP (>250 mg/kg) levels or evidence of active CD (≥1 ulceration in the ileum and/or colon) on endoscopy performed ≤3 months before week 0. ^cCIs were based on the Wald statistic with Mantel-Haenszel weight. Since the primary endpoint was not met, all the P-values are considered nominal, and statistical significance has not been established. ^dPatients with insufficient data at the designated analysis timepoint or who had a prohibited CD-related surgery, prohibited concomitant medication changes, or who discontinued the study agent due to the lack of efficacy or due to an AE indicative of worsening of CD prior to the designated analysis timepoint were not considered to have achieved the endpoint. ^eSchreiber (2023).² ^fMarín-Jiménez (2023).³ ^gSchreiber (2023).⁴

Click on the following links to related sections within the document: Phase 3b Study: POWER, Phase 3 Study: REScUE Study, and Retrospective Studies.
Abbreviations: CD, Crohn’s disease; CRP, C-reactive protein; FCP, fecal calprotectin; IV, intravenous; LoR, loss of response; PRO-2, patient-reported outcome-2; q4w, every 4 weeks; q8w, every 8 weeks; R, randomization; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease; UST, ustekinumab.
^hBossuyt (2025).⁵ ⁱSecondary LoR was defined per PRO-2, characterized by abdominal pain subscore >1 and stool frequency subscore >3, and confirmed by either an elevated biomarker (CRP >5 mg/L or FCP >250 μg/mg) or endoscopic signs of inflammation. ^jSteroid-free clinical remission was defined per PRO-2 (abdominal pain subscore ≤1 and stool frequency subscore ≤3), with FCP <250 µg/g and no steroids for 90 days prior to week 48. ^kEndoscopic remission was defined as SES-CD <3 at week 48. ^lEndoscopic response was defined as 50% decrease in SES-CD from baseline at week 48. ^mBiomarker remission was defined as CRP <5 mg/L and FCP <250 µg/g at week 48. ⁿYao (2023).⁶ ^oTen Bokkel Huinink (2021).⁷ ^pKopylov (2020).⁸ ^qHudson (2019).⁹

CLINICAL DATA

Phase 3b Study: POWER

Schreiber et al (2023)¹ conducted a phase 3b randomized, double-blind, multicenter study to compare the efficacy and safety of STELARA IV re-induction (single dose) with continued SC STELARA therapy in patients with CD who had LoR to the standard STELARA 90 mg SC q8w maintenance therapy.¹⁰

Study Design/Methods

Adult patients with moderately to severely active CD who had an initial response to STELARA IV induction therapy and later experienced LoR to STELARA SC maintenance therapy were included.¹¹
- Secondary LoR was defined as a Crohn’s Disease Activity Index (CDAI) score of ≥220 and ≤450 with at least 1 objective sign of inflammation: CRP; >3 mg/L or FCP levels (>250 mg/kg) or evidence of active CD (≥1 ulceration site in the ileum and/or colon) on endoscopy performed ≤3 months before week 0.
At baseline (week 0), patients were randomized to receive the following:
- STELARA ∼6 mg/kg IV→STELARA 90 mg SC at weeks 8 and 16
- STELARA 90 mg SC→STELARA 90 mg SC at weeks 8 and 16
The primary endpoint was clinical response (defined as a reduction in the CDAI score of ≥100 points from week 0 or a CDAI score of <150) at week 16.
Major secondary endpoints included the proportion of patients who achieved:
- Clinical remission at weeks 8 and 16 (defined as a CDAI score of <150)
- Clinical response at week 8
- Normalization of CRP levels (≤3 mg/L) and/or FCP levels (≤250 µg/g) at week 16 among patients with elevated CRP/FCP levels at baseline
Additional endpoints assessed at week 8 and/or week 16 included the following:
- Patient-reported outcomes (PROs; proportion of patients with Inflammatory Bowel Disease Questionnaire response at week 16 and mean change in unweighted PRO-2 from baseline)
- Endoscopic endpoints (proportion of patients with ≥25% improvement in Simple Endoscopic Score for Crohn’s Disease [SES-CD] from baseline, endoscopic response [defined as a reduction in SES-CD by 50% from baseline or an SES-CD of ≤3 or 0], endoscopic remission [defined as an SES-CD of ≤3 or 0], mean change from baseline in SES-CD, and endoscopic improvement [defined as a reduction in SES-CD of ≥3 points])

Results

Patient Characteristics

Among the 215 patients (STELARA IV, n=108; STELARA SC, n=107) included in the full analysis set at week 0, 96 (88.9%) and 99 (92.5%) patients in the STELARA IV and STELARA SC arms had a history of biologic treatment failure (characterized by primary nonresponse, secondary nonresponse, or intolerance), respectively.
At week 16, 92.6% and 86.0% of patients in the STELARA IV and STELARA SC arms completed treatment, respectively.

Efficacy

At week 16, a numerically greater proportion of patients in the STELARA IV arm had a clinical response (primary endpoint) compared with patients in the SC arm (49.1% vs 37.4%; P=0.089).
- Since the primary endpoint was not met, all the P-values for other endpoints are considered nominal, and statistical significance has not been established.
For efficacy results, see Table: Primary, Major Secondary, and Patient-Reported Outcomes at Weeks 8 and 16 and Table: Endoscopic Outcomes at Week 16.

Primary, Major Secondary, and Patient-Reported Outcomes at Weeks 8 and 16¹

	Week 8			Week 16
	STELARA IV (n=108)	STELARA SC (n=107)	Adjusted Difference, % (95% CI)^a	STELARA IV (n=108)	STELARA SC (n=107)	Adjusted Difference, % (95% CI)^a
Clinical response, n (%)^b	56 (51.9)	48 (44.9)	7.1 (-6.0 to 20.2)	53 (49.1)	40 (37.4)	11.5 (-1.5 to 24.5)
Clinical remission, n (%)^b	38 (35.2)	31 (29.0)	6.4 (-5.8 to 18.6)	36 (33.3)	29 (27.1)	5.9 (-6.0 to 17.8)
FCP and/or CRP normalization, n/N (%)^b	22/93 (23.7)	21/94 (22.3)	1.2 (-10.7 to 13.2)	31/93 (33.3)	14/94 (14.9)	18.5 (6.8-30.2)
IBDQ response, n (%)^b	-	-	-	64 (59.3)	46 (43.0)	16.3
Mean change from baseline in PRO-2 (unweighted)^c	-19.8	-12.8	-	-19.2	-12.5	-
Abbreviations: AE, adverse event; CD, Crohn’s disease; CI, confidence interval; CRP, C-reactive protein; FCP, fecal calprotectin; IBDQ, Inflammatory Bowel Disease Questionnaire; IV, intravenous; PRO-2, patient-reported outcome-2; SC, subcutaneous. ^aCIs were based on the Wald statistic with Mantel-Haenszel weight. Since the primary endpoint was not met, all the P-values are considered nominal, and statistical significance has not been established. ^bPatients with insufficient data at the designated analysis timepoint or who had a prohibited CD-related surgery, prohibited concomitant medication changes, or who discontinued the study agent due to lack of efficacy or due to an AE indicative of worsening of CD prior to the designated analysis timepoint were not considered to have achieved the endpoint. ^cPatients with insufficient data at the designated analysis timepoint or who had a prohibited CD-related surgery, prohibited concomitant medication changes, or who discontinued the study agent due to the lack of efficacy or due to an AE indicative of worsening of CD prior to the designated analysis timepoint had their baseline sum value carried forward.

Endoscopic Outcomes at Week 16¹^{, a,b}

	STELARA IV (n=59)	STELARA SC (n=58)
≥25% improvement in SES-CD from baseline, n (%)^c	40.7 (24)	15.5 (9)
Endoscopic response, n (%)^c	20.3 (12)	10.3 (6)
Endoscopic remission, n (%)^c	18.6 (11)	5.2 (3)
Mean change from baseline in SES-CD^d	-2.3	-0.8
Endoscopic improvement, n (%)^c	40.7 (24)	19.0 (11)
Abbreviations: AE, adverse event; CD, Crohn’s disease; FAS, full analysis set; IV, intravenous; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease. ^aSince the primary endpoint was not met, all the P-values are considered nominal, and statistical significance has not been established. ^bFor SES-CD analysis, only patients with an SES-CD of ≥3 at baseline in FAS were included. ^cPatients with insufficient data at the designated analysis timepoint or who had a prohibited CD-related surgery, prohibited concomitant medication changes, or who discontinued the study agent due to lack of efficacy or due to an AE indicative of worsening of CD prior to the designated analysis timepoint were not considered to have achieved the endpoint. ^dPatients with insufficient data at the designated analysis timepoint or who had a prohibited CD-related surgery, prohibited concomitant medication changes, or who discontinued the study agent due to the lack of efficacy or due to an AE indicative of worsening of CD prior to the designated analysis timepoint had their baseline sum value carried forward.

For efficacy outcomes in patients with or without a history of inadequate response or intolerance to a prior biologic, see Table: Primary and Major Secondary Endpoints in Patients with or Without a History of Inadequate Response or Intolerance to Prior Biologics.
For the association of clinical response to baseline demographics and disease characteristics, see Table: Proportion of Patients Who Achieved Clinical Response at Week 16 According to Baseline Characteristics.

Safety

At week 16, the proportion of patients who had ≥1 adverse event (AE; STELARA IV arm, 60.2%; STELARA SC arm, 61.7%) or serious AEs (STELARA IV, 5.6%; STELARA SC, 5.6%) was similar in the 2 treatment arms.
- The proportion of patients with infection was similar in the 2 treatment arms (STELARA IV, 23.1%; STELARA SC, 21.5%), and 1 serious infection was reported in each treatment arm.

Primary and Major Secondary Endpoints in Patients with or Without a History of Inadequate Response or Intolerance to Prior Biologics²

Outcome, n (%)	Week 8			Week 16
Outcome, n (%)	STELARA SC	STELARA IV	Adjusted Difference, % (95% CI)^a	STELARA SC	STELARA IV	Adjusted Difference, % (95% CI)^a
No history of prior biologic failure^b
n	8	12	-	8	12	-
Clinical response^{c, d}	3 (37.5)	4 (33.3)	-4.2	1 (12.5)	5 (41.7)	29.2
Clinical remission^{d, e}	3 (37.5)	4 (33.3)	-4.2	0 (0)	4 (33.3)	33.3
FCP and/or CRP normalization^{d, f, g, h}	-	-	-	1 (12.5)	2 (25.0)	12.5
History of inadequate response or intolerance to 1 prior biologic^b
N	37	33	-	37	33	-
Clinical response^{c, d}	21 (56.8)	20 (60.6)	4.7 (-18.4 to 27.7)	15 (40.5)	21 (63.6)	24.4 (2.0 to 46.8)
Clinical remission^{d, e}	15 (40.5)	14 (42.4)	-0.2 (-22.3 to 21.8)	12 (32.4)	15 (45.5)	11.8 (-9.9 to 33.4)
FCP and/or CRP normalization^{d, f, g, h}	-	-	-	2/31 (6.5)	12/28 (42.9)	37.6 (17.9-57.4)
History of inadequate response or intolerance to 2 prior biologics^b
N	35	35	-	35	35	-
Clinical response^{c, d}	12 (34.3)	19 (54.3)	22.0 (-0.2 to 44.3)	13 (37.1)	18 (51.4)	16.2 (-6.2 to 38.7)
Clinical remission^{d, e}	6 (17.1)	14 (40.0)	21.5 (1.3-41.6)	8 (22.9)	12 (34.3)	10.6 (-10.7 to 31.9)
FCP and/or CRP normalization^{d, f, g, h}	-	-	-	6/30 (20.0)	12/32 (37.5)	17.8 (-3.1 to 38.7)
History of inadequate response or intolerance to ≥3 prior biologics^b
N	27	28	-	27	28	-
Clinical response^{c, d}	12 (44.4)	13 (46.4)	-2.7 (-29.1 to 23.6)	11 (40.7)	9 (32.1)	-8.4 (-33.2 to 16.3)
Clinical remission^{d, e}	7 (25.9)	6 (21.4)	-2.0 (-24.3 to 20.2)	9 (33.3)	5 (17.9)	-11.0 (-33.3 to 11.2)
FCP and/or CRP normalization^{d, f, g, h}	-	-	-	5/25 (20.0)	5/25 (20.0)	3.8 (-18.8 to 26.4)
Abbreviations: CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; CI, confidence interval; CRP, C-reactive protein; FCP, fecal calprotectin; IV, intravenous; SC, subcutaneous. ^aSince the primary endpoint was not met, all the P-values are considered nominal, and statistical significance has not been established. ^bBiologics included tumor necrosis factor inhibitors or vedolizumab.^cClinical response was defined as a decrease of ≥100 points from week 0 or a CDAI score of <150 points. ^dPatients who had insufficient data at the designated analysis timepoint or who had a prohibited CD-related surgery, prohibited concomitant medication changes, or who discontinued the study agent due to lack of efficacy or due to an adverse event indicated to be caused by worsening CD prior to the designated analysis timepoint were not considered to have achieved the endpoint. ^eClinical remission was defined as a CDAI score of <150 points. ^fAbnormal CRP level was defined as a CRP level of >3 mg/L, and abnormal FCP concentration was defined as an FCP concentration of >250 μg/g. ^gNormalized CRP level was defined as a CRP level of ≤3 mg/L, and normalized FCP concentration was defined as an FCP concentration of ≤250 μg/g. When either the CRP or FCP value was abnormal at baseline and the value of the same parameter normalizes at week 16, patients were considered to be normalized at the designated analysis timepoint. ^hPatients who had insufficient data at the designated analysis timepoint had their last value carried forward.

Proportion of Patients Who Achieved Clinical Response at Week 16 According to Baseline Characteristics³^{, a, b}

Baseline and Clinical Disease Characteristics, n/N (%)	STELARA SC (n=107)	STELARA IV (n=108)	OR (95% CI)^{c, d}
CDAI score
≤300	24/68 (35.3)	30/68 (44.1)	1.4 (0.7-2.9)
>300	16/39 (41.0)	23/40 (57.5)	2.0 (0.8-4.8)
Prior CD-related surgery history
Total or subtotal colectomy	4/9 (44.4)	7/17 (41.2)	NE
Partial bowel resection	12/28 (42.9)	21/39 (53.8)	1.5 (0.5-4.0)
Current draining fistula	2/10 (20.0)	4/11 (36.4)	NE
Prior perianal surgery	4/21 (19.0)	14/23 (60.9)	5.8 (1.5-23.3)
Involved gastrointestinal areas
Ileum only	13/28 (46.4)	10/29 (34.5)	0.6 (0.2-2.0)
Colon only	11/22 (50.0)	10/24 (41.7)	0.7 (0.2-2.3)
Ileum and colon	16/55 (29.1)	33/55 (60.0)	3.6 (1.6-8.1)
Disease duration
<5 years	5/20 (25.0)	13/22 (59.1)	4.5 (1.2-17.4)
≥5 years	35/87 (40.2)	40/86 (46.5)	1.3 (0.7-2.4)
Prior failed biologics
0	1/8 (12.5)	5/12 (41.7)	NE
1	15/37 (40.5)	21/33 (63.6)	2.8 (1.0-7.6)
2	13/35 (37.1)	18/35 (51.4)	2.0 (0.7-5.3)
3	10/25 (40.0)	6/23 (26.1)	0.6 (0.2-2.0)
4	1/2 (50.0)	3/5 (60.0)	NE
Baseline biomarker levels
CRP ≤3 mg/L	12/32 (37.5)	10/29 (34.5)	0.9 (0.3-2.5)
CRP >3 mg/L	28/75 (37.3)	43/79 (54.4)	2.1 (1.1-4.0)
FCP ≤250 mg/kg	16/32 (50.0)	18/35 (51.4)	1.1 (0.4-2.8)
FCP >250 mg/kg	24/75 (32.0)	35/73 (47.9)	2.0 (1.0-4.0)
Abbreviations: CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; CI, confidence interval; CRP, C-reactive protein; FCP, fecal calprotectin; IV, intravenous; NE, not evaluated; OR, odds ratio; SC, subcutaneous. ^aClinical response was defined as a decrease of ≥100 points from week 0 or a CDAI score of <150 points. ^bPatients who had insufficient data at the designated analysis timepoint or who had a prohibited CD-related surgery, prohibited concomitant medication changes, or who discontinued the study agent due to lack of efficacy or due to an adverse event indicated to be caused by worsening CD prior to the designated analysis timepoint were not considered to have achieved clinical response, regardless of their CDAI score. ^cSince the primary endpoint was not met, all the P-values are considered nominal, and statistical significance has not been established. ^dOR, 95% CI for OR, and P-values were based on logistic regression.

Pharmacokinetic Analysis of the POWER Study

Schreiber et al (2023)⁴ presented the pharmacokinetics, exposure-response relationship, and immunogenicity analysis of the POWER study at week 16.

Study Design/Methods

Serum samples were collected at weeks 0, 8, and 16 for evaluation. Serum concentrations were evaluated using a proprietary immunoassay.
Efficacy outcomes were analyzed according to trough concentration groups at week 0 (undetectable, 0.17 to <0.8, 0.8 to <1.3, and ≥1.3 μg/mL) and concentration quartile groups at week 16.

Results

Serum ustekinumab concentration data was available from 215 patients (SC arm, n=107; IV arm, n=108) who had ≥1 blood samples collected.
At week 16, 63.9% (n=69) of patients in the IV arm and 41.1% (n=44) of patients in the SC arm had trough ustekinumab concentrations of ≥1.3 μg/mL. For details on ustekinumab serum levels, see Table: Summary of Ustekinumab Serum Concentrations.
Among patients with trough concentrations of ≥1.3 µg/mL, the proportion of patients with clinical response at week 16 was similar between treatment arms. However, there were more patients in the IV arm who achieved endoscopic remission at week 16 compared to those in the SC arm.
For details on ustekinumab exposure-response relationships, see Table: Exposure-Response Relationships at Week 16 by Trough Serum Concentrations and QG.

Summary of Ustekinumab Serum Concentrations⁴

Timepoint	Median Serum Concentrations (IQR), μg/mL
Timepoint	STELARA SC (n=107)	STELARA IV (n=108)
Week 0 pre-dose	1.26 (0.58-2.53)	1.30 (0.62-2.79)
Week 0 post-dose^a	1.47 (0.70-2.62)	105.62 (82.94-128.13)
Week 8	1.38 (0.85-2.61)	8.45 (4.25-10.49)
Week 16	1.41 (0.81-2.17)	2.99 (1.20-4.78)
Abbreviations: IQR, interquartile range; IV, intravenous; SC, subcutaneous. ^aThe post-dose sample was collected within 24 hours of STELARA administration.

Exposure-Response Relationships at Week 16 by Trough Serum Concentrations and QGs⁴

Outcomes at Week 16	Ustekinumab Trough Concentrations at Week 16 (μg/mL), n/N (%)
Outcomes at Week 16	Undetectable	0.17 to <0.8	0.8 to <1.3	≥1.3	Undetectable	0.17 to <0.8	0.8 to <1.3	≥1.3
Clinical response^{a, b}	0/1 (0)	5/18 (27.8)	8/16 (50.0)	24/44 (54.5)	0/2 (0)	8/15 (53.5)	3/7 (42.9)	39/69 (56.5)
Endoscopic remission^{b, c, d}	0/1 (0)	0/9 (0)	1/7 (14.3)	2/24 (8.3)	0/1 (0)	1/6 (16.7)	0/4 (0)	10/42 (23.8)
Outcomes at Week 16	Ustekinumab Trough Concentration QGs at Week 16^e, n/N (%)
Outcomes at Week 16	QG1 (≤q1)	QG2 (>q1 and ≤q2)	QG3 (>q2 and ≤q3)	QG4 (>q3)	QG1 (≤q1)	QG2 (>q1 and ≤q2)	QG3 (>q2 and ≤q3)	QG4 (>q3)
Clinical response^{a, b}	5/20 (25.0)	11/20 (55.0)	12/20 (60.0)	9/19 (47.4)	11/24 (45.8)	11/23 (47.8)	13/23 (56.5)	15/23 (65.2)
Endoscopic remission^{b, c, d}	0/10 (0)	1/11 (9.1)	0/9 (0)	2/11 (18.2)	1/11 (9.1)	2/10 (20.0)	3/14 (21.4)	5/18 (27.8)
Abbreviations: CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; IV, intravenous; q1, quartile 1; q2, quartile 2; q3, quartile 3; QG, quartile group; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease. ^aClinical response was defined as a decrease of ≥100 points from week 0 or a CDAI score of <150 points. ^bPatients who had insufficient data to calculate CDAI or SES-CD, a prohibited CD-related surgery, prohibited concomitant medication changes, or who discontinued the study agent due to lack of efficacy or due to an adverse event indicated to be of worsening CD prior to the designated analysis timepoint were considered not to be in clinical response or endoscopic remission. ^cEndoscopic remission was defined as an SES-CD of ≤3 or 0 for patients who entered the study with an SES-CD of 3. ^dEndoscopy was an optional procedure in the study; only 58 (SC arm) and 59 (IV arm) patients were included in the endoscopic analysis. ^eQuartiles were based on patients in each treatment group: SC arm, q1=0.81 µg/mL, q2=1.41 µg/mL, q3=2.17 µg/mL; IV arm, q1=1.20 µg/mL, q2=2.99 µg/mL, q3=4.78 µg/mL.

Through week 16, the incidence of antibodies to ustekinumab was low (SC, n=2; IV, n=0; 0.93% overall).

Phase 3 Study: REScUE

Bossuyt et al (2025)⁵ conducted a phase 3, randomized, placebo-controlled, double-blind, Belgian multicenter trial to evaluate the effect of 2 different re-induction treatment regimens with STELARA in adult patients with Crohn’s disease (CD).¹¹

Study Design/Methods

Patients who experienced a objective secondary loss of response to STELARA after STELARA induction therapy (>week 16) were included in this study.¹¹
Secondary LoR was defined per patient-reported outcome-2 (PRO-2; characterized by abdominal pain subscore >1 and stool frequency subscore >3) and confirmed by either an elevated biomarker (C-reactive protein [CRP] >5 mg/L or fecal calprotectin [FCP] >250 μg/mg) or endoscopic signs of inflammation.⁵
All patients received a single STELARA IV re-induction dose of ~6 mg/kg and then underwent randomization (1:1) to receive blinded maintenance therapy with STELARA 90 mg SC every 4 weeks (q4w) or every 8 weeks (q8w) for 48 weeks.
The primary endpoint was the proportion of patients achieving steroid-free clinical remission at week 48, with missing data handled using nonresponder imputation.
- Steroid-free clinical remission was defined per PRO-2 (abdominal pain subscore ≤1 and stool frequency subscore ≤3), with FCP <250 µg/g and no steroids for 90 days prior to week 48.

Results

Patient Characteristics

Among the 132 patients screened, 108 were included in the study; 67% of patients were female. The median age was 41 years (interquartile range [IQR], 32-54), and the median disease duration was 14 years (IQR, 7-22).
Prior exposure to anti-tumor necrosis factor (anti-TNF) therapy was reported in 92% of patients, and STELARA was the first-line advanced therapy in 7% of patients.
For efficacy outcomes, see Table: Efficacy Outcomes at Week 48.
The time to first clinical remission was similar between both groups (P=0.82). No new safety signals were observed.

Efficacy Outcomes at Week 48⁵

Outcome, n (%)	Treatment Regimen		P-Value
Outcome, n (%)	STELARA 90 mg SC q4w (n=54)	STELARA 90 mg SC q8w (n=54)	P-Value
Steroid-free clinical remission^a (primary endpoint)	9 (17)	8 (16)	0.96
Endoscopic remission^b	5 (10)	3 (6)	0.52
Endoscopic response^c	11 (22)	6 (12)	0.23
Biomarker remission^d	20 (38)	13 (26)	0.19
Abbreviations: CRP, C-reactive protein; FCP, fecal calprotectin; PRO-2, patient-reported outcome-2; q4w, every 4 weeks; q8w, every 8 weeks; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn's Disease. ^aSteroid-free clinical remission was defined per PRO-2 (ie, abdominal pain subscore ≤1 and stool frequency subscore ≤3), with FCP <250 µg/g and no steroids for 90 days prior to week 48. ^bEndoscopic remission was defined as SES-CD <3 at week 48. ^cEndoscopic response was defined as 50% decrease in SES-CD from baseline at week 48. ^dBiomarker remission was defined as CRP <5 mg/L and FCP <250 µg/g at week 48.

Retrospective Studies

Yao et al (2023)⁶ conducted a single-center, retrospective, observational, cohort study to evaluate the efficacy and safety of STELARA IV re-induction in patients with refractory CD in a real-world setting.

Study Design/Methods

Patients included in this study were those who failed to achieve clinical remission at week 16 following STELARA treatment initiation.
These patients were then dose optimized according to 1 of the following strategies:
- Shortened dosing intervals: SC q8w or q4w dosing.
- IV re-induction (weight-based dosing) followed by SC q8w or q4w dosing.
Data specific to patients receiving IV re-induction are reported below.
The primary outcome was clinical remission (CDAI score of <150) at 3 months after treatment optimization.
Secondary outcomes included clinical, biochemical, and endoscopic responses and remission and safety assessments at 1 year after initiating STELARA.
- Clinical response was defined as a decrease in the CDAI score of >70 points from the baseline value.
- Endoscopic remission was defined as an SES-CD of ≤2.
- Endoscopic response was defined as a decrease in the SES-CD of >50% from the baseline value.

Results

Patient Characteristics

Overall, 128 patients who received STELARA treatment optimization (interval reduction, n=105; IV re-induction, n=23) were included.
Reasons for treatment optimization included partial response (71.9%) and LoR (28.1%) at week 16.
The median interval between STELARA initiation and IV re-induction was 16 weeks (IQR, 9-18 weeks).
The follow-up duration was 23.0 weeks (range, 13-17 weeks) for the IV re-induction cohort.

Efficacy

For the effect of IV re-induction on CRP values and CDAI scores, see Table: Changes in CRP Value and CDAI Score Between Pre- and Post-IV Re-Induction.

Changes in CRP Value and CDAI Score Between Pre- and Post-IV Re-Induction ⁶

Parameter	Median (IQR)	Median Time to Assessment (Range), Weeks	P-Value
Change in CRP value between pre- and post-IV re-induction	3.2 (-0.8 to 8.4)	8.0 (8.0 to 8.0)	NS
Change in CDAI score between pre- and post-IV re-induction	69.0 (10.7 to 151.0)	8.0 (8.0 to 16.0)	<0.05
Abbreviations: CDAI, Crohn’s Disease Activity Index; CRP, C-reactive protein; IQR, interquartile range; IV, intravenous; NS, not significant.

For clinical outcomes in patients who received IV re-induction, see Table: Biochemical, Clinical, and Endoscopic Outcomes After IV Re-Induction.

Biochemical, Clinical, and Endoscopic Response After IV Re-Induction⁶

Outcome	Patients with IV Re-Induction (n=23)	P-Value
CRP normalization^a, n/N (%)	13/23 (56.5)	NS
Clinical response, n/N (%)	18/23 (78.3)	NS
Clinical remission, n/N (%)	16/23 (69.6)	NS
Endoscopic response, n/N (%)	12/22 (54.5)	NS
Endoscopic remission, n/N (%)	7/22 (31.8)	NS
Abbreviation: CRP, C-reactive protein; IV, intravenous; NS, not significant. ^aCRP normalization was defined as CRP <4 mg/L.

Safety

There was 1 AE in the IV re-induction cohort (n=1, 4.3%). This patient experienced an allergic reaction to STELARA and discontinued treatment.

Ten Bokkel Huinink et al (2021)⁷ conducted a multicenter retrospective cohort study to evaluate the effectiveness and safety of re-induction with IV STELARA after secondary LoR in patients with CD.

Study Design/Methods

The primary outcome was drug survival at weeks 20 and 52 of STELARA maintenance therapy after the second dose of IV STELARA; patients who maintained STELARA therapy were considered to have had a response or remission to the second dose of IV STELARA.
Secondary outcomes were the proportion of patients in clinical remission (Harvey-Bradshaw Index [HBI] ≤4) at weeks 20 and 52, nonresponse (defined as no or insufficient response to the second IV dose of STELARA within 8 weeks from re-induction), and incidence of AEs.

Results

Overall, 166 patients were included in this study, and 31 received a second dose of IV STELARA after a median duration of 10.4 years (IQR, 6.7-16.6 years).
Among the 31 patients, all had received ≥1 prior anti-TNF therapy, 24 had failed ≥2 prior anti-TNF therapies, and 20 had received vedolizumab prior to initiating STELARA.
Prior to IV re-induction, 10 patients were already optimized by shortening the dosing interval.
The median treatment duration between initial treatment and re-induction with IV STELARA was 11.1 months (IQR, 6.9-19.5 months).
Overall, 5 (16%), 17 (55%), and 9 (29%) patients received re-induction with STELARA at a dose of 260 mg, 390 mg, and 520 mg, respectively.
At the time of the IV re-induction, all patients showed clinical (median HBI, 8), biochemical (median FCP level, 413 μg/g; median CRP concentration, 12.5 mg/L), or endoscopic disease activity.
After the re-induction therapy, 17 (61%) and 10 (32%) patients started subsequent STELARA maintenance therapy with q8w and q4w dosing, respectively.
Overall, 21 (74%) and 20 (71%) patients were still receiving STELARA maintenance therapy at weeks 20 and 52, respectively.
- In total, 4 of 10 patients (40%) on a q4w dosing interval discontinued STELARA treatment after a median treatment duration of 3.9 months (IQR, 2.04-4.24 months), and 1 of 17 patients (6%) on a q8w dosing interval discontinued STELARA treatment after 6.9 months (P=0.047).
Four patients did not receive maintenance therapy due to nonresponse with IV re-induction.
At baseline, due to biochemical disease activity, 9 patients who were in clinical remission received IV re-induction.
In the total population, 11 of 30 (37%), 15 of 27 (56%), and 13 of 29 (45%) patients were in clinical remission at weeks 8, 20, and 52, respectively.
- Among patients without clinical remission at baseline, 23%, 44%, and 40% of patients were in clinical remission at weeks 8, 20, and 52, respectively.
Overall, 9 patients (29%) discontinued STELARA within 1 year of receiving the second dose of IV STELARA either due to nonresponse (n=5; 56%), LoR (n=3; 33%), or AE (n=1; 11%). Median treatment duration until cessation was 1.8 months (IQR, 1.5-4.2 months) after re-induction.
Overall, 6 patients required hospitalization during STELARA treatment due to ileus or severe active disease.
Three possibly related AEs were reported after IV re-induction, including a lower urinary tract infection, intestinal bacterial overgrowth, and pruritus.
One malignancy (melanoma requiring surgical resection) was reported during follow-up.

Kopylov et al (2020)⁸ evaluated the efficacy and safety of dose escalation of STELARA in patients with active CD after nonresponse or LoR to STELARA 90 mg SC q8w maintenance therapy in a multicenter retrospective cohort study. This analysis included a subset of patients who were evaluated for the efficacy of STELARA IV re-induction.

Patients in the study received ≥2 doses of STELARA (IV induction of 6 mg/kg followed by 90 mg SC injection) and an IV re-induction (6 mg/kg) instead of a scheduled SC dose, or SC dose escalation to q4w or every 6 weeks (q6w) dosing, or a combination of IV re-induction and SC dose escalation.
The primary endpoint was clinical response, which was defined as a change in HBI ≥3 or a change in the CDAI score of ≥70 at week 16 after a dose escalation strategy.
Overall, 142 patients were included in the study, and of those, 14 received an IV re-induction and 17 had a combination of IV re-induction and dosing interval shortening.
At week 16, clinical response was achieved by 5 of 14 patients (35.7%) who received IV re-induction and 10 of 16 patients (62.5%) who received both IV re-induction and q4w dose escalation.
Overall, 5 of 14 patients (35.6%) who received IV re-induction and 1 of 17 patients (5.9%) who received both IV re-induction and SC dose escalation discontinued STELARA due to clinical nonresponse.

Hudson et al (2019)⁹ conducted a retrospective cohort study of patients with CD who received a second STELARA IV loading dose after secondary LoR.

Patients who lost response to STELARA after initial IV standard induction followed by SC maintenance therapy and received a second STELARA IV loading dose following the standard weight-based dosing recommendations were included in the study.
Response was defined as a resolution or improvement of clinical symptoms that led to a second IV infusion.
Among 372 patients treated with STELARA, 18 (5%) received a second IV loading dose after experiencing secondary LoR to their initial IV induction dose.
The patients had all failed prior biologic therapy and received STELARA as second-line (22%), third-line (27%), fourth-line (33%), fifth-line (6%), or sixth-line (11%) therapy.
After IV re-induction, clinical response was observed in 15 patients (83%). Three patients (17%) did not respond, and STELARA was stopped.
Among the 15 patients remaining on STELARA, 5 (33%) continued q8w dosing, 6 (40%) were on q6w dosing, and 4 (27%) required q4w dosing.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 07 February 2025.

Summarized in this response are relevant data from a phase 3b study (POWER), a phase 3 study (REScUE), and retrospective studies.

References

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1	Schreiber S, Lee S, van der Woude CJ, et al. Efficacy and safety of intravenous ustekinumab re-induction therapy in Crohn’s disease patients with secondary loss of response to ustekinumab maintenance therapy: week 16 results from the POWER trial. Poster presented at: European Crohn’s and Colitis Organisation (ECCO); March 1-4, 2023; Copenhagen, Denmark.
2	Schreiber S, Lee S, van der Woude CJ, et al. Clinical outcomes and biomarker normalisation response at week 16 in patients with inadequate response or intolerance to prior biologics in the POWER trial. Abstract presented at: 31st United European Gastroenterology (UEG) Week; October 14-17, 2023; Copenhagen, Denmark and Virtual.
3	Marín-Jiménez I, Schreiber S, Lee S, et al. Analysis of baseline characteristics associated with clinical response to ustekinumab IV re-induction strategy in patients with Crohn’s disease in the POWER trial. Abstract presented at: 31st United European Gastroenterology (UEG) Week; October 14-17, 2023; Copenhagen, Denmark and Virtual.
4	Schreiber S, Lee S, van der Woude CJ, et al. Pharmacokinetics, exposure-response relationships, and immunogenicity in Crohn’s disease patients with ustekinumab secondary loss of response following ustekinumab IV re-induction: results from the week 16 analysis of the POWER study. Poster presented at: 31st United European Gastroenterology (UEG) Week; October 14-17, 2023; Copenhagen, Denmark and Virtual.
5	Bossuyt P, Rahier JF, Baert F, et al. Low remission recapture after ustekinumab dose optimization in Crohn’s disease: results of the randomized placebo-controlled double blind REScUE study. Abstract presented at: European Crohn’s and Colitis Organisation (ECCO); February 19-22, 2025; Berlin, Germany.
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7	Ten Bokkel Huinink S, Biemans V, Duijvestein M, et al. Re-induction with intravenous ustekinumab after secondary loss of response is a valid optimization strategy in Crohn’s disease. Eur J Gastroenterol Hepatol. 2021;33(1S):e783-e788.
8	Kopylov U, Hanzel J, Liefferinckx C, et al. Effectiveness of ustekinumab dose escalation in Crohn’s disease patients with insufficient response to standard-dose subcutaneous maintenance therapy. Aliment Pharmacol Ther. 2020;52(1):135-142.
9	Hudson J, Barnes E, Herfarth H. Ustekinumab intravenous reinduction therapy is effective at recapturing response in patients with Crohn’s disease. Abstract presented at: American College of Gastroenterology (ACG) 2019; October 25-30, 2019; San Antonio, TX.
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