Give all the clinical data published for USTEKINUMAB, abstracts for finished clinical trials of USTEKINUMAB
Scope and mechanism
Ustekinumab is a monoclonal antibody targeting the shared p40 subunit of interleukin-12 and interleukin-23. The provided literature covers randomized clinical trial evidence in Crohn’s disease, ulcerative colitis, and plaque psoriasis, including placebo-controlled induction/maintenance programs and several active-comparator trials where ustekinumab served either as the investigational agent or comparator.
Crohn’s disease
UNITI-1, UNITI-2, and IM-UNITI: pivotal induction and maintenance trials
The pivotal Crohn’s disease program evaluated intravenous ustekinumab induction followed by subcutaneous maintenance in adults with moderately to severely active Crohn’s disease. UNITI-1 enrolled 741 patients with primary or secondary nonresponse to TNF antagonists or unacceptable TNF-antagonist toxicity; UNITI-2 enrolled 628 patients with failure or intolerance of conventional therapy. Patients received a single intravenous dose of ustekinumab 130 mg, ustekinumab approximately 6 mg/kg, or placebo. The primary induction endpoint was clinical response at week 6, defined as a Crohn’s Disease Activity Index (CDAI) decrease of at least 100 points or CDAI <150 (Feagan et al., 2016).
In UNITI-1, week-6 response rates were 34.3% with ustekinumab 130 mg and 33.7% with ~6 mg/kg, compared with 21.5% with placebo, corresponding to absolute differences of 12.8 and 12.2 percentage points, respectively; both comparisons were statistically significant (P≤0.003). In UNITI-2, response rates were higher overall: 51.7% and 55.5% with ustekinumab 130 mg and ~6 mg/kg versus 28.7% with placebo, absolute differences of 23.0 and 26.8 percentage points (P<0.001 for both) (Feagan et al., 2016).
Responders entered IM-UNITI, where 397 ustekinumab induction responders were randomized to ustekinumab 90 mg subcutaneously every 8 weeks, every 12 weeks, or placebo. At week 44, clinical remission occurred in 53.1% with every-8-week dosing and 48.8% with every-12-week dosing versus 35.9% with placebo. Absolute differences were 17.2 and 12.9 percentage points, respectively (P=0.005 and P=0.04). Adverse-event rates were reported as similar across groups (Feagan et al., 2016).
SEAVUE: ustekinumab versus adalimumab in biologic-naïve Crohn’s disease
SEAVUE was a phase 3b, randomized, double-blind, active-comparator trial at 121 sites in 18 countries, enrolling biologic-naïve adults with CDAI 220–450 and at least one ulcer on baseline endoscopy. Patients received ustekinumab ~6 mg/kg IV on day 0, then 90 mg SC every 8 weeks, or adalimumab induction/maintenance through week 56 (Sands et al., 2021).
Of 386 randomized patients, 191 received ustekinumab and 195 adalimumab. Treatment discontinuation before week 52 occurred in 29/191 (15%) ustekinumab-treated patients versus 46/195 (24%) adalimumab-treated patients. The primary endpoint, clinical remission at week 52, was achieved by 124/191 (65%) with ustekinumab and 119/195 (61%) with adalimumab; the between-group difference was 4 percentage points with a 95% CI −6 to 14 and P=0.42, indicating no significant difference. Serious infections occurred in 4/191 (2%) versus 5/195 (3%), and no deaths occurred through week 52 (Sands et al., 2021).
Head-to-head trials with IL-23 p19 inhibitors
In a phase 3b open-label randomized trial with blinded endpoint assessment, risankizumab was compared with ustekinumab in anti-TNF–experienced moderate-to-severe Crohn’s disease. In the full intention-to-treat population, treatment completion was 230/255 (90.2%) with risankizumab and 193/265 (72.8%) with ustekinumab. Risankizumab was noninferior for week-24 CDAI remission: 58.6% versus 39.5%, adjusted difference 18.4 percentage points (95% CI 6.6–30.3). It was superior for week-48 endoscopic remission: 31.8% versus 16.2%, adjusted difference 15.6 percentage points (95% CI 8.4–22.9; P<0.001). Adverse-event incidence appeared similar (Peyrin-Biroulet et al., 2024).
In GALAXI-1, ustekinumab was a reference arm against guselkumab. The phase 2 trial randomized 309 patients in the primary efficacy population, including 63 to ustekinumab. At week 48, CDAI remission occurred in 37/63 (59%) ustekinumab patients; endoscopic response in 19/63 (30%); and endoscopic remission in 4/63 (6%) (Danese et al., 2023). Safety through week 48 showed adverse events in 60/71 (85%) ustekinumab-treated patients, with an event rate of 350.7 per 100 patient-years; nasopharyngitis and upper respiratory infections occurred in 12/114 (11%) and 8/114 (7%), respectively, among guselkumab- or ustekinumab-treated patients, and no active tuberculosis, opportunistic infections, or deaths were reported (Danese et al., 2023).
In VIVID-1, mirikizumab was compared with ustekinumab and placebo in 1065 efficacy-evaluable patients; 287 received ustekinumab. Ustekinumab’s efficacy results were not fully provided in the text, but safety data showed serious adverse events in 33/309 (10.7%) ustekinumab-treated patients, and one death occurred in the ustekinumab group, not considered drug-related (Ferrante et al., 2024).
Ulcerative colitis: UNIFI induction and maintenance
UNIFI evaluated ustekinumab in moderate-to-severe ulcerative colitis as 8-week IV induction followed by 44-week SC maintenance. In induction, 961 patients were randomized to ustekinumab 130 mg (n=320), ustekinumab ~6 mg/kg (n=322), or placebo (n=319). Clinical remission at week 8 occurred in 15.6% and 15.5% of ustekinumab groups versus 5.3% with placebo, an absolute benefit of about 10 percentage points for both doses (P<0.001) (Sands et al., 2019).
Induction responders were rerandomized to ustekinumab 90 mg SC every 12 weeks (n=172), every 8 weeks (n=176), or placebo (n=175). At week 44, remission occurred in 38.4% with every-12-week dosing and 43.8% with every-8-week dosing versus 24.0% with placebo, absolute differences of 14.4 and 19.8 percentage points (P=0.002 and P<0.001) (Sands et al., 2019).
Safety was broadly comparable with placebo. Through 52 weeks, among 825 ustekinumab-exposed patients, there were two deaths—acute respiratory distress syndrome and hemorrhage from esophageal varices—and seven cancers: prostate, colon, renal papillary, rectal cancer, and three nonmelanoma skin cancers. Among 319 placebo-treated patients, there were no deaths and one testicular cancer (Sands et al., 2019).
Plaque psoriasis active-comparator trials
UltIMMa-1 and UltIMMa-2: risankizumab versus ustekinumab
The replicate phase 3 UltIMMa trials randomized adults with moderate-to-severe plaque psoriasis to risankizumab, ustekinumab, or placebo. Ustekinumab was dosed per label at 45 mg or 90 mg. In UltIMMa-1, 100 patients received ustekinumab; in UltIMMa-2, 99 received ustekinumab (Gordon et al., 2018).
At week 16, ustekinumab achieved PASI90 in 42/100 (42.0%) in UltIMMa-1 and 47/99 (47.5%) in UltIMMa-2. Risankizumab was superior, with PASI90 rates of 75.3% and 74.8%, giving ustekinumab-adjusted differences of 33.5 percentage points (95% CI 22.7–44.3) and 27.6 percentage points (95% CI 16.7–38.5), both P<0.0001. Static Physician’s Global Assessment 0/1 occurred with ustekinumab in 63.0% and 61.6%, versus 87.8% and 83.7% with risankizumab (Gordon et al., 2018).
BE VIVID: bimekizumab versus ustekinumab
BE VIVID was a 52-week phase 3 trial in 567 randomized patients with moderate-to-severe plaque psoriasis: bimekizumab (n=321), ustekinumab (n=163), or placebo (n=83). At week 16, PASI90 was achieved by 81/163 (50%) receiving ustekinumab versus 273/321 (85%) receiving bimekizumab; the risk difference favoring bimekizumab was 35 percentage points (95% CI 27–43; P<0.0001). Investigator’s Global Assessment response occurred in 87/163 (53%) with ustekinumab versus 270/321 (84%) with bimekizumab, 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-treated patients (Reich et al., 2020).
Overall interpretation
Across the provided completed clinical-trial evidence, ustekinumab consistently demonstrated statistically significant induction and maintenance efficacy versus placebo in Crohn’s disease and ulcerative colitis, with generally comparable adverse-event rates to placebo or active comparators. In Crohn’s disease, efficacy was strongest in conventional-therapy failure populations and maintained through subcutaneous dosing. In head-to-head Crohn’s trials, ustekinumab performed similarly to adalimumab in biologic-naïve disease but was outperformed on selected endpoints by newer IL-23 p19 inhibitors. In plaque psoriasis, ustekinumab was effective, but newer agents such as risankizumab and bimekizumab achieved substantially higher PASI90 and global-assessment response rates.