Give all abstracts for finished clinical trials of Ustekinumab
Scope and interpretation
The supplied text contains abstracts or abstract fragments for several completed or reported clinical trials involving ustekinumab, either as the investigational therapy or as an active comparator. Ustekinumab is a monoclonal antibody targeting the shared p40 subunit of interleukin-12 and interleukin-23. The trials span Crohn’s disease, ulcerative colitis, plaque psoriasis, and recent-onset type 1 diabetes. Below is a consolidated, abstract-style scientific summary of the finished/reported trials for which the provided text gives sufficient information.
1. Crohn’s disease: UNITI-1, UNITI-2, and IM-UNITI
Objective and design
Ustekinumab was evaluated for induction and maintenance therapy in adults with moderately to severely active Crohn’s disease. Two randomized induction trials were conducted: UNITI-1, enrolling patients with primary or secondary nonresponse to tumor necrosis factor antagonists or unacceptable adverse effects, and UNITI-2, enrolling patients in whom conventional therapy had failed or caused unacceptable adverse effects. Responders entered IM-UNITI, a maintenance trial (Feagan et al., 2016).
Population and interventions
UNITI-1 included 741 patients, and UNITI-2 included 628 patients. Patients received a single intravenous dose of ustekinumab, either 130 mg or approximately 6 mg/kg, or placebo. In IM-UNITI, 397 induction responders were randomized to subcutaneous ustekinumab 90 mg every 8 weeks, 90 mg every 12 weeks, or placebo (Feagan et al., 2016).
Results and conclusion
At week 6, clinical response rates were significantly higher with ustekinumab than placebo. In UNITI-1, response occurred in 34.3% with 130 mg and 33.7% with ~6 mg/kg, versus 21.5% with placebo; both comparisons had P≤0.003. In UNITI-2, response occurred in 51.7% and 55.5% with ustekinumab, versus 28.7% with placebo; both P<0.001. In IM-UNITI, week-44 remission occurred in 53.1% of patients receiving ustekinumab every 8 weeks and 48.8% every 12 weeks, versus 35.9% with placebo (P=0.005 and P=0.04, respectively). Adverse-event rates were similar across groups. Overall, intravenous ustekinumab induced response, and subcutaneous ustekinumab maintained remission in Crohn’s disease (Feagan et al., 2016).
2. Crohn’s disease: SEAVUE, ustekinumab versus adalimumab
Objective and design
SEAVUE was a randomized, double-blind, active-comparator phase 3b trial comparing ustekinumab monotherapy with adalimumab monotherapy in biologic-naïve adults with moderately to severely active Crohn’s disease (Sands et al., 2022).
Population and interventions
The trial enrolled 386 patients at 121 hospitals or private practices in 18 countries. Patients had CDAI scores of 220–450, inadequate response or intolerance to conventional therapy, corticosteroid dependence, and at least one baseline ulcer. Participants were randomized 1:1 to ustekinumab, approximately 6 mg/kg intravenously on day 0, then 90 mg subcutaneously every 8 weeks, or adalimumab, 160 mg day 0, 80 mg week 2, then 40 mg every 2 weeks, through week 56 (Sands et al., 2022).
Results and conclusion
Before week 52, treatment discontinuation occurred in 29/191 patients (15%) receiving ustekinumab and 46/195 (24%) receiving adalimumab. At week 52, clinical remission, defined as CDAI <150, occurred in 124/191 (65%) ustekinumab-treated patients versus 119/195 (61%) adalimumab-treated patients. The between-group difference was 4 percentage points with a 95% CI of −6 to 14, and was not statistically significant (P=0.42). Serious infections occurred in 4/191 (2%) ustekinumab patients and 5/195 (3%) adalimumab patients. No deaths occurred through week 52. Both biologics were highly effective, with no significant difference in the primary outcome (Sands et al., 2022).
3. Ulcerative colitis: UNIFI induction and maintenance trial
Objective and design
The UNIFI program evaluated ustekinumab as 8-week induction and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis (Sands et al., 2019).
Population and interventions
A total of 961 patients were randomized to intravenous ustekinumab 130 mg (n=320), ustekinumab approximately 6 mg/kg (n=322), or placebo (n=319). Patients responding to induction were rerandomized to subcutaneous ustekinumab 90 mg every 12 weeks (n=172), 90 mg every 8 weeks (n=176), or placebo (n=175). Clinical remission was defined by a total Mayo score ≤2 with no subscore >1 (Sands et al., 2019).
Results and conclusion
At week 8, clinical remission occurred in 15.6% of patients receiving 130 mg and 15.5% receiving ~6 mg/kg, compared with 5.3% receiving placebo; both comparisons had P<0.001. At week 44, remission was achieved by 38.4% receiving ustekinumab every 12 weeks and 43.8% every 8 weeks, compared with 24.0% receiving placebo (P=0.002 and P<0.001, respectively). Serious adverse events were similar to placebo. Through 52 weeks, among 825 ustekinumab-exposed patients, there were 2 deaths and 7 cancers; among 319 placebo patients, there were no deaths and 1 cancer. Ustekinumab was superior to placebo for both induction and maintenance of remission (Sands et al., 2019).
4. Crohn’s disease: risankizumab versus ustekinumab head-to-head trial
Objective and design
A phase 3b, multicenter, open-label, randomized controlled trial with blinded endpoint assessment compared risankizumab with ustekinumab in patients with moderate-to-severe Crohn’s disease who had inadequate response or unacceptable side effects with anti-TNF therapy (Peyrin-Biroulet et al., 2024).
Results and conclusion
In the full intention-to-treat population, 230/255 (90.2%) risankizumab patients and 193/265 (72.8%) ustekinumab patients completed all assigned treatments. Risankizumab was noninferior to ustekinumab for week-24 clinical remission: 58.6% versus 39.5%, adjusted difference 18.4 percentage points, 95% CI 6.6 to 30.3. Risankizumab was superior for week-48 endoscopic remission: 31.8% versus 16.2%, adjusted difference 15.6 percentage points, 95% CI 8.4 to 22.9, P<0.001. Adverse-event incidence appeared similar. Thus, ustekinumab was effective but was outperformed by risankizumab on endoscopic remission in this anti-TNF-experienced Crohn’s population (Peyrin-Biroulet et al., 2024).
5. Plaque psoriasis: UltIMMa-1 and UltIMMa-2
Objective and design
UltIMMa-1 and UltIMMa-2 were replicate phase 3, randomized, double-blind, placebo- and ustekinumab-controlled trials assessing risankizumab versus ustekinumab or placebo in adults with moderate-to-severe chronic plaque psoriasis. Both trials were completed (Gordon et al., 2018).
Results and conclusion
UltIMMa-1 randomized 506 patients: risankizumab n=304, ustekinumab n=100, placebo n=102. UltIMMa-2 randomized 491 patients: risankizumab n=294, ustekinumab n=99, placebo n=98. At week 16, PASI90 was achieved in UltIMMa-1 by 42.0% of ustekinumab patients versus 75.3% with risankizumab; the risankizumab advantage over ustekinumab was 33.5 percentage points, 95% CI 22.7–44.3, P<0.0001. In UltIMMa-2, PASI90 occurred in 47.5% with ustekinumab versus 74.8% with risankizumab; adjusted difference 27.6 percentage points, 95% CI 16.7–38.5, P<0.0001. Treatment-emergent adverse events were broadly similar across groups. Ustekinumab was active, but risankizumab showed superior skin-clearance efficacy (Gordon et al., 2018).
6. Plaque psoriasis: BE VIVID, bimekizumab versus ustekinumab
BE VIVID was a 52-week, multicenter, randomized, double-blind, active- and placebo-controlled phase 3 trial in moderate-to-severe plaque psoriasis. Among 567 randomized patients, 321 received bimekizumab, 163 received ustekinumab, and 83 received placebo. At week 16, PASI90 occurred in 273/321 (85%) bimekizumab patients versus 81/163 (50%) ustekinumab patients, risk difference 35 percentage points, 95% CI 27–43, P<0.0001. Investigator’s Global Assessment response occurred in 84% versus 53%, risk difference 30 percentage points, 95% CI 22–39, P<0.0001. Serious treatment-emergent adverse events over 52 weeks occurred in 13/163 (8%) ustekinumab patients. Bimekizumab was more efficacious, while ustekinumab served as a standard active comparator (Reich et al., 2021).
7. Type 1 diabetes in adolescents
A multicenter, double-blind, randomized phase 2 trial evaluated ustekinumab in 72 adolescents aged 12–18 years with recent-onset type 1 diabetes. Ustekinumab was well tolerated, with no increase in adverse events. At 12 months, stimulated C-peptide, reflecting β-cell function, was 49% higher in the ustekinumab group than control, meeting the prespecified primary endpoint (P=0.02). Preservation of C-peptide correlated with reductions in pathogenic T-helper subsets, including TH17.1 cells (P=0.04) and proinsulin-specific IL-17A-secreting T cells (P=0.0003). The authors concluded that ustekinumab may reduce β-cell loss, though confirmation in a larger study is required (Tatovic et al., 2024).
8. Crohn’s disease: VIVID-1, mirikizumab with ustekinumab active comparator
VIVID-1 was a completed global phase 3, randomized, double-blind, double-dummy, placebo- and active-controlled treat-through trial in moderately-to-severely active Crohn’s disease. Patients were randomized to mirikizumab, ustekinumab, or placebo; the efficacy population included 1065 patients: mirikizumab n=579, ustekinumab n=287, placebo n=199. The provided text states that both mirikizumab coprimary endpoints versus placebo were met, including week-12 patient-reported clinical response combined with week-52 endoscopic response or CDAI remission. However, the excerpt is truncated before full ustekinumab comparative results are provided (Ferrante et al., 2024).
Overall synthesis
Across completed or reported trials, ustekinumab demonstrated clinically meaningful efficacy in Crohn’s disease and ulcerative colitis, with statistically significant benefits over placebo for induction and maintenance. In active-comparator studies, ustekinumab performed similarly to adalimumab in biologic-naïve Crohn’s disease but was less effective than newer IL-23p19 or IL-17A/F pathway agents for selected endpoints in Crohn’s disease and psoriasis. Safety findings were generally consistent across studies, with adverse-event rates often similar to comparator or placebo groups.