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 published clinical data span inflammatory bowel disease—Crohn’s disease and ulcerative colitis—and dermatology, where ustekinumab is frequently used as an active comparator in psoriasis trials. The strongest direct efficacy data in the supplied text are from randomized induction/maintenance programs in Crohn’s disease and ulcerative colitis, with additional head‑to‑head or reference-arm evidence against adalimumab, risankizumab, guselkumab, bimekizumab, and mirikizumab.
1. Ulcerative colitis: UNIFI induction and maintenance
The pivotal ulcerative colitis evidence comes from the UNIFI program in adults with moderate-to-severe ulcerative colitis. In the 8‑week induction trial, 961 patients were randomized to intravenous ustekinumab 130 mg (n=320), weight-based ustekinumab approximating 6 mg/kg (n=322), or placebo (n=319). The primary endpoint was clinical remission at week 8, defined by Mayo score criteria: total Mayo score ≤2 with no subscore >1. Clinical remission occurred in 15.6% with ustekinumab 130 mg and 15.5% with ~6 mg/kg, compared with 5.3% with placebo; both comparisons were statistically significant, P<0.001 (Sands et al., 2019).
Responders entered a 44‑week maintenance trial and were re-randomized to subcutaneous ustekinumab 90 mg every 12 weeks (n=172), every 8 weeks (n=176), or placebo (n=175). At week 44, remission rates were 38.4% with every‑12‑week dosing and 43.8% with every‑8‑week dosing, versus 24.0% with placebo; P=0.002 and P<0.001, respectively (Sands et al., 2019). Safety was broadly similar to placebo for serious adverse events. Through 52 weeks, among 825 ustekinumab-exposed patients there were two deaths—acute respiratory distress syndrome and hemorrhage from esophageal varices—and seven cancers, including prostate, colon, renal papillary, rectal, and three nonmelanoma skin cancers. In 319 placebo-treated patients, there were no deaths and one testicular cancer (Sands et al., 2019).
Interpretation: Ustekinumab showed statistically robust induction and maintenance efficacy in moderate-to-severe ulcerative colitis, with remission differences versus placebo of about 10 percentage points during induction and 14–20 percentage points during maintenance.
2. Crohn’s disease: UNITI-1, UNITI-2, and IM-UNITI
The pivotal Crohn’s disease program evaluated intravenous induction and subcutaneous maintenance therapy. UNITI‑1 included 741 patients with primary or secondary nonresponse to TNF antagonists or unacceptable TNF-related adverse effects. UNITI‑2 included 628 patients with failure or intolerance of conventional therapy. Patients received a single IV ustekinumab dose—130 mg or ~6 mg/kg—or placebo. The primary induction endpoint was clinical response at week 6, defined as a ≥100‑point CDAI decrease or CDAI <150 (Feagan et al., 2016).
In UNITI‑1, week‑6 response occurred in 34.3% with 130 mg ustekinumab and 33.7% with ~6 mg/kg, versus 21.5% with placebo; P≤0.003 for both comparisons. In UNITI‑2, response rates were higher: 51.7% and 55.5% with ustekinumab versus 28.7% with placebo; P<0.001 for both doses (Feagan et al., 2016). Responders then entered IM‑UNITI; 397 ustekinumab induction responders were randomized to 90 mg subcutaneously every 8 weeks, every 12 weeks, or placebo. At week 44, remission occurred in 53.1% with every‑8‑week dosing and 48.8% with every‑12‑week dosing, compared with 35.9% with placebo; P=0.005 and P=0.04, respectively (Feagan et al., 2016). Adverse-event rates were similar across treatment groups.
Interpretation: Ustekinumab was effective both after TNF failure and after conventional therapy failure, with larger induction effects in the conventional-therapy failure population.
3. Crohn’s disease head-to-head data
SEAVUE: ustekinumab versus adalimumab in biologic-naïve Crohn’s disease
SEAVUE was a phase 3b, randomized, double-blind, active-comparator trial in biologic-naïve adults with moderate-to-severe Crohn’s disease and at least one baseline ulcer. Patients received ustekinumab IV ~6 mg/kg at day 0 followed by 90 mg SC every 8 weeks, or adalimumab induction and 40 mg every 2 weeks, both as monotherapy through week 56. A total of 386 patients were randomized: ustekinumab n=191 and adalimumab n=195 (Sands et al., 2021).
At week 52, clinical remission, defined as CDAI <150, occurred in 124/191 patients, or 65%, with ustekinumab versus 119/195, or 61%, with adalimumab. The between-group difference was 4 percentage points, 95% CI −6 to 14; p=0.42, indicating no significant difference (Sands et al., 2021). Discontinuation before week 52 occurred in 15% of ustekinumab patients and 24% of adalimumab patients. Serious infections were reported in 4/191, or 2%, with ustekinumab and 5/195, or 3%, with adalimumab; no deaths occurred (Sands et al., 2021).
Risankizumab versus ustekinumab after anti-TNF failure
A phase 3b randomized trial compared risankizumab with ustekinumab in moderate-to-severe Crohn’s disease after inadequate response or intolerance to anti-TNF therapy. In the full intention-to-treat population, 230/255 patients, or 90.2%, completed assigned risankizumab treatment versus 193/265, or 72.8%, with ustekinumab. Risankizumab was noninferior to ustekinumab for clinical remission at week 24: 58.6% versus 39.5%, adjusted difference 18.4 percentage points, 95% CI 6.6–30.3. It was superior for endoscopic remission at week 48: 31.8% versus 16.2%, adjusted difference 15.6 percentage points, 95% CI 8.4–22.9; P<0.001 (Peyrin-Biroulet et al., 2024). Adverse events appeared similar between groups.
Interpretation: Ustekinumab remains an effective Crohn’s comparator, but newer IL‑23p19 inhibition may outperform it for endoscopic outcomes after anti‑TNF failure.
4. Ustekinumab as reference or active comparator in Crohn’s disease trials
In GALAXI‑1, a phase 2 Crohn’s disease trial of guselkumab, ustekinumab was included as a reference arm: IV ~6 mg/kg at week 0 followed by 90 mg SC at week 8. At week 12, guselkumab showed significant CDAI reductions and remission versus placebo, and the abstract states that efficacy of ustekinumab versus placebo was also demonstrated (Sandborn et al., 2022). In the 48‑week GALAXI‑1 maintenance report, the ustekinumab arm included 63 patients in the primary efficacy analysis; 37/63, or 59%, achieved CDAI clinical remission at week 48, 19/63, or 30%, had endoscopic response, and 4/63, or 6%, had endoscopic remission (Danese et al., 2023). Adverse events occurred in 60/71 ustekinumab-treated patients, or 85%, corresponding to 350.7 events per 100 patient-years; common infections included nasopharyngitis in 12/114, or 11%, and upper respiratory infection in 8/114, or 7%, among ustekinumab recipients (Danese et al., 2023).
In phase 3 GALAXI‑2 and GALAXI‑3, ustekinumab again served as an active comparator against guselkumab. Serious adverse events occurred in 35 ustekinumab-treated participants, or 12%, with an incidence rate of 18.4 events per 100 participant-years; no deaths were reported (Panaccione et al., 2024).
5. Psoriasis active-comparator data
Ustekinumab has substantial comparator data in plaque psoriasis. In UltIMMa‑1 and UltIMMa‑2, risankizumab was compared with placebo and ustekinumab in moderate-to-severe plaque psoriasis. Ustekinumab PASI90 rates at week 16 were 42.0% in UltIMMa‑1 and 47.5% in UltIMMa‑2, compared with risankizumab rates of 75.3% and 74.8%, respectively; risankizumab was superior to ustekinumab, with adjusted differences of 33.5 percentage points and 27.6 percentage points, both p<0.0001 (Gordon et al., 2018). Ustekinumab sPGA 0/1 rates were 63.0% and 61.6%, again lower than risankizumab (Gordon et al., 2018).
In BE VIVID, bimekizumab was compared with ustekinumab and placebo. At week 16, PASI90 occurred in 81/163, or 50%, of ustekinumab patients versus 273/321, or 85%, with bimekizumab; risk difference 35%, 95% CI 27–43; p<0.0001. IGA response occurred in 87/163, or 53%, with ustekinumab versus 270/321, or 84%, with bimekizumab; risk difference 30%, 95% CI 22–39; p<0.0001. Serious treatment-emergent adverse events over 52 weeks occurred in 13/163, or 8%, of ustekinumab-treated patients (Reich et al., 2020).
6. Comparative evidence from network meta-analyses
A Crohn’s disease network meta-analysis found ustekinumab significantly increased odds of induction remission compared with certolizumab in biologic-naïve patients, with OR 2.63, 95% CI 1.10–6.28 (Singh et al., 2021). In ulcerative colitis, a network meta-analysis found ustekinumab superior to placebo for induction remission, OR 2.92, 95% CI 1.31–6.51, with no differences between active interventions for adverse events or serious adverse events (Lasa et al., 2021). In psoriasis, Cochrane network meta-analyses concluded that several newer biologics—particularly IL‑17 and IL‑23p19 inhibitors—achieved higher PASI90 rates than ustekinumab, while serious adverse event comparisons were limited by low event counts and low-to-moderate certainty (Sbidian et al., 2021), (Sbidian et al., 2022).
Overall conclusion
Across completed randomized trials, ustekinumab demonstrates clinically meaningful and statistically significant efficacy for induction and maintenance in moderate-to-severe Crohn’s disease and ulcerative colitis, with generally placebo-like serious adverse-event rates in pivotal studies. In biologic-naïve Crohn’s disease, it performed similarly to adalimumab at 52 weeks. In psoriasis and newer Crohn’s disease head-to-head studies, ustekinumab remains effective but is often outperformed on stringent skin-clearance or endoscopic endpoints by newer IL‑23p19 or IL‑17 pathway agents.