UstekinumabRx

Trade Names: Stelara

Drug Class:  IL-12 and IL-23 inhibitor

Preparations: Subcutaneous injection: 45 mg/0.5 mL  and 90 mg/mL (1 mL), both available as vials and prefilled syringes

Dose: Adults with psoriatic arthritis: 45 mg by subcutaneous injection at weeks 0 and 4 and then every 12 weeks thereafter;  for adults with plaque psoriasis who weigh less than 100 kg – same dose as for psoriatic arthritis; for those weighing more than 100 kg – 90 mg at weeks 0 and 4 and then every 12 weeks thereafter.

Indications: Plaque psoriasis; active psoriatic arthritis – can be used with or without methotrexate

Mechanism of Action: Human monoclonal antibody binds to the p40 subunit of IL-12 and IL-23 interfering with cytokine signalling

Contraindications: Hypersensitivity, active infection, avoid live virus vaccines, avoid BCG for 1 year before, during, and 1 year following treatment

Precautions: Increased risk of serious infections including TB and fungal. Exclude latent or active TB with a skin test or TB blood test (interferon-gamma release assays or IGRA). Caution in debilitated or high risk of infection.

Monitoring: After therapy started, additional TB testing may be indicated for individuals likely to have exposure to TB. Monitor for skin cancer.

Pregnancy Risk: B

Adverse Effects
Common: Minor infections, injection site reactions, headache, upper respiratory tract infections
Less common: Allergy, rash, serious infection (bacterial, viral and also atypical and opportunistic infections), antibodies to ustekinumab
Rare: Anaphylaxis, reversible posterior leukoencephalopathy syndrome, malignancy particularly skin cancer, pustular psoriasis

Drug Interactions
Live virus vaccines and BCG: Avoid
Other biologics and potent immunosuppressants: Avoid, increased risk of infection

Patient Instructions: Avoid live virus vaccines. Stop injections if have an infection. May increase risk of skin cancer.

Comments:  In psoriasis trials PASI score decreased approximately 70%  vs. 4% on placebo. In psoriatic arthritis trials ACR20 responses occurred with ustekinumab 45 mg in approximately  43% vs 22% on placebo. Psoriatic arthritis placebo-controlled trials are difficult to blind because associated psoriasis is  very responsive to ustekinumab. Individuals genetically deficient in IL12/IL23 have increased risks of disseminated mycobacterial, BCG and salmonella infections; infection risks from ustekinumab are not well characterized. Limited information on other long-term risks (e.g. malignancy, cardiovascular).

Clinical Pharmacology: Half-life is 10-126 days. Biologic agents are not metabolized and have few drug interactions.

Cost: $$$$$

BIBLIOGRAPHY

McInnes IB, Kavanaugh A, Gottlieb AB, et al Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet 2013;382:780-9.PMID: 23769296.