Product: Stelara

Company: Centocor Ortho Biotech

Pharmacologic class: Interleukin (IL)-12 and IL-23 antagonist

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Active ingredient: Ustekinumab 45 mg/0.5 mL; solution for subcutaneous (SC) injection; preservative-free.

Indication: Moderate-to- severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy.

Pharmacology: Ustekinumab is a human immunoglobulin G1k monoclonal antibody against the p40 subunit of IL-12 and IL-23. These cytokines are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. Ustekinumab was shown in vitro 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.

Clinical trials: Two double-blind, placebo-controlled studies were conducted in patients aged 18 years or older with plaque psoriasis who were candidates for phototherapy or systemic therapy. The patients had at least 10% body surface involvement and a Psoriasis Area and Severity Index (PASI) score >12; baseline PASI scores ranged from about 17 to 18. Patients with guttate, erythrodermic, or pustular psoriasis were excluded.

For both studies, subjects were randomized to ustekinumab 45 mg, 90 mg, or placebo. Those randomized to ustekinumab received 45 mg or 90 mg, regardless of weight, at Weeks 0, 4, and 16. Those randomized to placebo received placebo at Weeks 0 and 4 and were crossed over to ustekinumab 45 mg or 90 mg at Weeks 12 and 16. The end points were the proportion of subjects who achieved at least a 75% reduction in the PASI score from baseline to Week 12 (PASI 75) and treatment success (cleared or minimal) on the Physician’s Global Assessment (PGA), which indicates the clinician’s overall assessment of psoriasis, focusing on thickness, induration, erythema, and scaling. Baseline PGA score was marked or severe in 44% of the 766 subjects in Study 1 and in 40% of the 1,230 subjects in Study 2.

In Study 1, 67% of patients achieved PASI 75 in the ustekinumab 45-mg group, 66% in the 90-mg, and 3% in the placebo group. In Study 2, 67% of patients given 45 mg ustekinumab and 76% of patients given ustekinumab 90 mg achieved PASI 75, compared with 4% for placebo.

Adults: >18 years: <100 kg: 45 mg SC once then four weeks later, then once every 12 weeks. >100 kg: 90 mg once then four weeks later, then once every 12 weeks. Rotate injection site.

Children: <18 years: not recommended.

Precautions: Active infections: not recommended. Increased risk of serious or fatal infections, especially in IL-12/IL-23 genetically- deficient patients (e.g., mycobacteria, salmonella, BCG vaccines). Monitor for new infection; discontinue if serious infection develops. Conditions that predispose to infection. Test for and treat latent TB prior to initiating therapy. Avoid close contact with live-vaccine recipients. History of malignancies. Discontinue if reversible posterior leukoencephalopathy syndrome occurs or is suspected. Elderly. Pregnancy (Cat. B). Nursing mothers.

Interactions: Concomitant live vaccines, other immunosuppressants, phototherapy: not recommended. Do not give BCG vaccines during or within one year of starting or stopping ustekinumab. Non-live vaccines: may get suboptimal response. May affect CYP450 substrates.

Adverse reactions: Nasopharyngitis, upper respiratory tract infection, headache, fatigue; infections, malignancies, reversible posterior leukoencephalopathy syndrome.

How supplied: Single-use vial (0.5 mL)—1

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