CLINICAL DATA

Phase 3b Study: POWER

Schreiber et al (2025)¹ conducted a phase 3b, randomized, double-blind, multicenter study to compare the efficacy and safety of STELARA intravenous (IV) reinduction (single dose) with continued subcutaneous (SC) STELARA therapy in patients with Crohn’s disease (CD) who had a loss of response (LoR) to the standard STELARA 90 mg SC every 8 weeks (q8w) maintenance therapy.¹¹

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.¹²
  • 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: C-reactive protein (CRP); >3 mg/L or fecal calprotectin (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, 16, and 24
  • STELARA 90 mg SC→STELARA 90 mg SC at weeks 8, 16, and 24
• 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 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 included the following:
  • Clinical response, clinical remission, and normalization of CRP and/or FCP at week 24.
  • Change from baseline in the unweighted PRO-2 score at weeks 8, 16, and 24. PRO-2 is the CDAI components of the total number of liquid or very soft stools and the abdominal pain score in the prior 7 days.
  • Corticosteroid-free response (CDAI score decrease ≥100 from baseline or CDAI score <150 and no steroid use ≥30 days before timepoint) at week 24. The proportion of patients with corticosteroid-free response at week 24 among patients who are receiving corticosteroid at baseline, and the proportion of patients with corticosteroid-free remission (defined as a CDAI score <150 among patients who were receiving corticosteroids at baseline) at week 24 were also evaluated.
  • Endoscopic endpoints at week 16: 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], proportion of patients with ≥25% improvement in Simple Endoscopic Score for Crohn’s Disease [SES-CD] from baseline, mean change from baseline in SES-CD, and endoscopic improvement [defined as a reduction in SES-CD of ≥3 points]).

Results

Patient Characteristics

• A total of 215 patients (STELARA IV, n=108; STELARA SC, n=107) were included in the study; the mean age was 40.9 years, and 58% of patients were female.
• At week 36, 75.9% (n=82) and 72.0% (n=77) of patients in the STELARA IV and STELARA SC arms completed the final follow-up, 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, Other Endpoints and Patient-Reported Outcomes at Weeks 8, 16 and 24 and Table: Endoscopic Outcomes at Week 16.

• 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 36, the proportion of patients who had ≥1 adverse event (AE) was 70.4% in the STELARA IV arm and 72.9% in the STELARA SC arm; see Table: Safety Outcomes at Week 36.

Pharmacokinetic Analysis of the POWER Study

Study Design/Methods

• Serum samples were collected at weeks 0, 8, and 16 for evaluation. Serum concentrations were evaluated using a proprietary immunoassay.⁴
• 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 16.⁴

Results

• Serum ustekinumab concentration data was available from 215 patients (SC arm, n=107; IV arm, n=108) who had ≥1 blood samples collected.⁴
• 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.⁴ 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.⁴
• For details on ustekinumab exposure-response relationships, see Table: Exposure-Response Relationships at Week 16 by Trough Serum Concentrations and QG.

• Through week 16, the incidence of antibodies to ustekinumab was low (SC, n=2; IV, n=0; 0.93% overall).⁴

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 reinduction treatment regimens with STELARA in adult patients with CD.¹²

Study Design/Methods

• Patients who experienced an objective secondary LoR to STELARA after STELARA induction therapy (>week 16) were included in this study.¹² 
• Secondary 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.⁵ 
• All patients received a single STELARA IV reinduction 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 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.

Efficacy

• 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.

Pharmacokinetics and Pharmacodynamics

• Serum samples were collected at weeks 4, 8, 12, 20, 28, 36, and 48 for evaluation.⁶
• Baseline ustekinumab trough levels at LoR were similar between groups and aligned with prior suggested target levels.⁶
  • Median (IQR): 90 mg SC q4w, 1.39 µg/mL (0.84-2.74); 90 mg SC q8w, 1.31 µg/mL (0.91-2.34); P>0.9
• At week 8, ustekinumab trough levels were significantly higher with q4w vs q8w dosing⁶:
  • Median (IQR): 10.8 µg/mL (8.0-15.9) vs 8.2 µg/mL (4.9-11.1); P=0.002
• At week 48, difference persisted⁶:
  • Median (IQR): 6.0 µg/mL (4.8-9.6) vs 2.1 µg/mL (1.6-2.9); P<0.001
• At baseline, week 8, and week 48⁶:
  • No significant association between ustekinumab trough levels and steroid-free clinical or endoscopic remission was observed.
  • Significant association with biomarker remission: odds ratio, 2.98, 1.12, and 1.35, respectively; all P<0.01
• Per quartile analysis at week 48, the lowest quartile (<0.9 µg/mL) showed the lowest steroid-free clinical remission in both groups.⁶

Retrospective Studies

De Marco et al (2025)¹⁴ conducted a single-center, retrospective, observational cohort study to evaluate remission in patients with CD who underwent IV reinduction with STELARA.

Study Design/Methods

• Patients included in the study were those who had clinically or biochemically active CD, completed induction with STELARA, and underwent dose escalation with STELARA.
• Active CD was defined as Harvey Bradshaw Index (HBI) ≥5, FCP >250 µg/g, or CRP >5 mg/L.
• The primary outcome was clinical and biochemical remission.

Results

• Overall, 39 patients were included in this study, and 36% of patients underwent IV reinduction.
• By the 3-month follow-up, the primary outcome was achieved in 30.8% (n=12) of patients.
  • Among the 12 patients who achieved the primary outcome (clinical and biochemical remission), 7 patients (58.3%) underwent IV reinduction.

Yao et al (2023)⁷ conducted a single-center, retrospective, observational, cohort study to evaluate the efficacy and safety of STELARA IV reinduction 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 reinduction (weight-based dosing) followed by SC q8w or q4w dosing
• Data specific to patients receiving IV reinduction 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 reinduction, 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 reinduction was 16 weeks (IQR, 9-18 weeks).
• The follow-up duration was 23.0 weeks (range, 13-17 weeks) for the IV reinduction cohort.

Efficacy

• For the effect of IV reinduction on CRP values and CDAI scores, see Table: Changes in CRP Value and CDAI Score Between Pre- and Post-IV Reinduction.

• For clinical outcomes in patients who received IV reinduction, see Table: Biochemical, Clinical, and Endoscopic Response After IV Reinduction.

Safety

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

Ten Bokkel Huinink et al (2021)⁸ conducted a multicenter retrospective cohort study to evaluate the effectiveness and safety of reinduction 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 (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 reinduction), 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 reinduction, 10 patients were already optimized by shortening the dosing interval.
• The median treatment duration between initial treatment and reinduction with IV STELARA was 11.1 months (IQR, 6.9-19.5 months).
• Overall, 5 (16%), 17 (55%), and 9 (29%) patients received reinduction with STELARA at a dose of 260 mg, 390 mg, and 520 mg, respectively.
• At the time of the IV reinduction, 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 reinduction 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 reinduction.
• At baseline, due to biochemical disease activity, 9 patients who were in clinical remission received IV reinduction.
• 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 reinduction.
• Overall, 6 patients required hospitalization during STELARA treatment due to ileus or severe active disease.
• Three possibly related AEs were reported after IV reinduction, 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)⁹ 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 reinduction.

• Patients in the study received ≥2 doses of STELARA (IV induction of 6 mg/kg followed by 90 mg SC injection) and an IV reinduction (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 reinduction 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 reinduction and 17 had a combination of IV reinduction and dosing interval shortening.
• At week 16, clinical response was achieved by 5 of 14 patients (35.7%) who received IV reinduction and 10 of 16 patients (62.5%) who received both IV reinduction and q4w dose escalation.
• Overall, 5 of 14 patients (35.6%) who received IV reinduction and 1 of 17 patients (5.9%) who received both IV reinduction and SC dose escalation discontinued STELARA due to clinical nonresponse.

Hudson et al (2019)¹⁰ 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 reinduction, 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 12 December 2025.

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