Stelara (ustekinumab) - 4 indications 

Scroll down for information on each indication:

• for the treatment of plaque psoriasis, psoriatic arthritis and Crohn's disease; approved September 2009
• for the treatment of moderately to severely active ulcerative colitis; approved October 2019

General Information

Stelara (ustekinumab) is a human IgG1k monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit used by both the interleukin (IL)-12 and IL-23 cytokines. IL-12 and IL-23 are naturally occurring cytokines that are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation.

Stelara is specifically indicated for: 

• the treatment of patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
• for the treatment of adult patients with active psoriatic arthritis, alone or in combination with methotrexate (MTX)
• for the treatment of adult patients with moderately to severely active Crohn’s disease
• for the treatment of adult patients with moderately to severely active ulcerative colitis

Stelara is supplied as a solution for subcutaneous or intravenous injection. Scroll down for recommended dosing/administration for each indication.

Mechanism of Action

Stelara (ustekinumab) is a human IgG1k monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit used by both the interleukin (IL)-12 and IL-23 cytokines. IL-12 and IL-23 are naturally occurring cytokines that are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. In in vitro models, ustekinumab was shown to disrupt IL-12 and IL-23 mediated signaling and cytokine cascades by disrupting the interaction of these cytokines with a shared cell-surface receptor chain, IL-12 ß1.

Side Effects

Adverse events associated with the use of Stelara for psoriasis and psoriatic arthritis may include, but are not limited to, the following:

• Nasopharyngitis
• Upper respiratory tract infection
• Headache
• Fatigue
• Diarrhea

Adverse events associated with the use of Stelara for Crohn's disease may include, but are not limited to, the following:

Crohn’s Disease, induction

• vomiting

Crohn’s Disease, maintenance

• nasopharyngitis
• injection site erythema
• vulvovaginal candidiasis/mycotic infection
• bronchitis
• pruritus
• urinary tract infection
• sinusitis

Adverse events associated with the use of Stelara for ulcerative colitis may include, but are not limited to, the following:

Ulcerative colitis, induction

• nasopharyngitis

Ulcerative colitis, maintenance

• nasopharyngitis
• headache
• abdominal pain
• influenza
• fever
• diarrhea
• sinusitis
• fatigue
• nausea

Indications 1- 3: for the treatment of plaque psoriasis, psoriatic arthritis and Crohn's disease

approved September 2009

Dosing/Administration

Plaque psoriasis:

• For patients weighing ≤100 kg (220 lbs): 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks.
• For patients weighing >100 kg (220 lbs): 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks. The 45 mg dose was also shown to be efficacious in this population. However, 90 mg resulted in greater efficacy in these subjects.

Pediatrics: Administer Stelara subcutaneously at Weeks 0 and 4, then every 12 weeks thereafter. The recommended dose for pediatric patients (6-17 years old) based on body weight:

• less than 60 kg: 0.75 mg/kg
• 60 kg to 100 kg: 45 mg
• more than 100 kg: 90 mg

For pediatric patients weighing less than 60 kg, please see the drug label for recommended dosing.

Psoriatic Arthritis Adult Subcutaneous Dose:

• The recommended dosage is 45 mg administered subcutaneously initially and 4 weeks later, followed by 45 mg administered subcutaneously every 12 weeks. For patients with co-existent moderate-to-severe plaque psoriasis weighing greater than 100 kg, the recommended dosage is 90 mg administered subcutaneously initially and 4 weeks later, followed by 90 mg administered subcutaneously every 12 weeks.

Crohn's Disease Initial Adult Intravenous Dosage:

 A single intravenous infusion using weight-based dosing:

• Weight Range (kilogram): Up to 55 kg | Recommended Dosage: 260 mg (2 vials)
• Weight Range (kilogram): Greater than 55 kg to 85 kg | Recommended Dosage: 390 mg (3 vials)
• Weight Range (kilogram): Greater than 85 kg | Recommended Dosage: 520 mg (4 vials)

Crohn's Disease Maintenance Adult Subcutaneous Recommended Dosage

• A subcutaneous 90 mg dose 8 weeks after the initial intravenous dose, then every 8 weeks thereafter

Clinical Trial Results

Psoriasis Adults

The FDA approval of Stelara was based on two multicenter, randomized, double-blind, placebo-controlled studies: STUDY 1 (n=766) and STUDY 2 (n=1,230). All subjects were 18 years of age and older with plaque psoriasis over a minimum body surface area of 10%, and Psoriasis Area and Severity Index (PASI) score >12, and who were candidates for phototherapy or systemic therapy. In both studies, subjects were randomized to the following groups: placebo at Weeks 0 and 4 followed by crossover to Stelara (either 45 mg or 90 mg) at Weeks 12 and 16; or Stelara 45 mg or 90 mg doses, regardless of weight, at Weeks 0, 4, and 16. In both studies, the endpoints were the proportion of subjects who achieved at least a 75% reduction in PASI score (PASI 75) from baseline to Week 12 and treatment success (cleared or minimal) on the Physician’s Global Assessment (PGA). In STUDY 1, the PASI75 response was reached by 3%, 67% and 66% of the placebo and Stelara 45 mg and 90 mg doses, respectively. The PGA of Cleared or Minimal was reached by 4%, 59% and 61% of the placebo, Stelara 45 mg and 90 mg doses, respectively. Subjects in STUDY 1 were evaluated through Week 52. At Week 40, those who were PASI 75 responders at both Weeks 28 and 40 were re-randomized to either continued dosing of Stelara at Week 40 or to withdrawal of therapy (placebo at Week 40). At Week 52, 89% of subjects re-randomized to Stelara treatment were PASI 75 responders compared with 63% of subjects re-randomized to placebo (treatment withdrawal after Week 28 dose). In STUDY 2, the PASI75 response was reached by 4%, 67% and 76% of the placebo and Stelara 45 mg and 90 mg doses, respectively. The PGA of Cleared or Minimal was reached by 4%, 68% and 73% of the placebo, Stelara 45 mg and 90 mg doses, respectively. In subjects who weighed <100 kg, response rates were similar with both the 45 mg and 90 mg doses; however, in subjects who weighed >100 kg, higher response rates were seen with 90 mg dosing compared with 45 mg dosing.

Psoriasis Pediatrics

The FDA approval of Stelara for pediatric use was based on results from the CADMUS Junior study. The open-label, single-arm, multicenter phase 3 clinical trial enrolled 44 patients with moderate to severe plaque psoriasis. Results showed that 77 percent of patients achieved clear or almost clear skin, at week 12 after two doses. Secondary endpoints included the proportion of patients achieving 75 percent or 90 percent improvement in their Psoriasis Area and Severity Index (PASI) score at week 12 compared to baseline. Study results showed 84 percent and 64 percent of patients achieved a PASI 75 response and PASI 90 response, respectively. 

Psoriatic Arthritis

Two randomized, double-blind, placebo-controlled studies, PsA STUDY 1 (n=615) and PsA STUDY 2 (n=312), enrolled adult patients 18 years of age and older with active PsA (>5 swollen joints and ≥5 tender joints) despite non-steroidal anti-inflammatory (NSAID) or disease modifying antirheumatic (DMARD) therapy. Patients were randomized to receive treatment with Stelara 45 mg, 90 mg, or placebo subcutaneously at Weeks 0 and 4 followed by every 12 weeks (q12w) dosing. Approximately 50% of patients continued on stable doses of MTX . The primary endpoint was the percentage of patients achieving ACR 20 response at Week 24. In both studies, a greater proportion of patients achieved ACR 20, ACR 50 and PASI 75 response in the Stelara 45 mg and 90 mg groups compared to placebo at Week 24.

Crohn's disease

Three randomized, double-blind, placebo-controlled clinical studies were conducted in adult patients with moderately to severely active Crohn’s disease (Crohn’s Disease Activity Index [CDAI] score of 220 to 450). There were two 8-week intravenous induction studies (UNITI-1 (n=741) and UNITI-2 (n=627)) followed by a 44-week subcutaneous randomized withdrawal maintenance study, representing 52 weeks of therapy. In clinical studies of patients who were either new to, experienced with, or failed biologic therapy (TNF blockers), between 34% (UNITI-1 study) and 56% (UNITI-2 study) of patients experienced relief from their Crohn's disease symptoms in six weeks after receiving the one-time intravenous (IV) infusion of Stelara. Noticeable improvement was observed as early as three weeks. Additionally, the majority of those who responded to induction dosing and continued treatment with Stelara subcutaneous maintenance doses every 8 weeks were in remission at the end of 44 weeks (52 weeks from initiation of the induction dose).

Indication 4 - for the treatment of moderately to severely active ulcerative colitis

approved October 2019

Dosing/Administration

Ulcerative Colitis Initial Adult Intravenous Dosage:

 A single intravenous infusion using weight-based dosing:

• Weight Range (kilogram): Up to 55 kg | Recommended Dosage: 260 mg (2 vials)
• Weight Range (kilogram): Greater than 55 kg to 85 kg | Recommended Dosage: 390 mg (3 vials)
• Weight Range (kilogram): Greater than 85 kg | Recommended Dosage: 520 mg (4 vials)

Ulcerative Colitis Maintenance Adult Subcutaneous Recommended Dosage

• A subcutaneous 90 mg dose 8 weeks after the initial intravenous dose, then every 8 weeks thereafter

Clinical Trial Results

FDA approval was based on the Phase III UNIFI Study designed to evaluate the safety and efficacy of ustekinumab induction and maintenance dosing for the treatment of moderate to severe ulcerative colitis in adults who demonstrated an inadequate response to, or were unable to tolerate, conventional (i.e., corticosteroids, immunomodulators) or biologic (i.e., one or more TNF blockers and/or vedolizumab) therapies. Both the induction and maintenance studies are randomised, double-blind, placebo-controlled, parallel group studies. The Induction study was of at least 8 weeks’ duration for each participant. Participants achieving clinical response in the induction study were eligible for the maintenance study. The maintenance study was 44 weeks’ in duration. The primary endpoint of the induction study was clinical remission at Week 8 and the primary endpoint for the maintenance study was clinical remission at Week 44 among responders to a single intravenous (IV) ustekinumab infusion. At Week 8: 15.6% of patients receiving 130 mg ustekinumab and 15.5% of patients receiving ~6 mg/kg ustekinumab achieved clinical remission, compared with 5.3% of patients receiving placebo.