ustekinumab


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ustekinumab

(uss-te-kin-oo-mab) ,

Stelara

(trade name)

Classification

Therapeutic: antipsoriatics
Pharmacologic: interleukin antagonists
Pregnancy Category: B

Indications

Moderate to severe plaque psoriasis in patients who are candidates for phototherapy or systemic therapy.Active psoriatic arthritis (as monotherapy or with methotrexate)

Action

Binds to the p40 protein subunit used by both the interleukin (IL)-12 and IL-23 cytokines. These cytokines that are involved in inflammatory and immune responses, including natural killer cell activation and CD4+ T-cell differentiation and activation. Binding to interleukins antagonizes their effects, disrupting IL-12 and IL-23 mediated signaling and cytokine cascades.

Therapeutic effects

Decrease in area and severity of psoriatic lesions.
Decreased progression of psoriatic arthritis

Pharmacokinetics

Absorption: Well absorbed following subcutaneous administration.
Distribution: Unknown.
Metabolism and Excretion: Broken down by catabolic processes into peptides and amino acids.
Half-life: 15–46 days.

Time/action profile

ROUTEONSETPEAK†DURATION
45 mg subcutunknown13.5 days12 wk
90 mg subcutunknown7 days12 wk
†Blood levels

Contraindications/Precautions

Contraindicated in: HypersensitivityActive untreated infection.
Use Cautiously in: History of known malignancy or tuberculosis (possibility of reactivation); >60 yr, history of prolonged immunosuppressant therapy, or history of PUVA treatment (↑ risk of skin cancer) Obstetric: Use only if potential benefit justifies potential risk to the fetus.; Lactation: Unknown risks to infant from gastrointestinal/systemic exposure should be weighed against known benefits of breast-feeding.; Pediatric: Safety and effectiveness not established.
Exercise Extreme Caution in: Chronic infection or history of recurrent infection.

Adverse Reactions/Side Effects

Central nervous system

  • Reversible Posterior Leukoencephalopathy Syndrome (life-threatening)
  • fatigue (most frequent)
  • headache (most frequent)

Local

  • erythema

Miscellaneous

  • anaphylaxis (life-threatening)
  • angioedema (life-threatening)
  • infection (life-threatening)
  • malignancy (life-threatening)

Interactions

Drug-Drug interaction

May ↓ antibody response to and ↑ risk of adverse reactions from live vaccines.May ↓ desired antibody response to non-live vaccines.May affect the activity of CYP450 drug-metabolizing enzymes; when treatment is started during concurrent CYP450 substrates, especially those with a narrow therapeutic indices, including warfarin and cyclosporine ; appropriate monitoring and dose adjustment should be carried out.

Route/Dosage

Psoriasis

Subcutaneous (Adults ≤100 kg) 45 mg initially and 4 wk later, then 45 mg q 12 wk.
Subcutaneous (Adults >100 kg) 90 mg initially and 4 wk later, then 90 mg q 12 wk.

Psoriatic Arthritis

Subcutaneous (Adults) 45 mg initially and 4 wk later, then 45 mg q 12 wk.
Subcutaneous (Adults >100 kg with concomitant moderate-severe plaque psoriasis) 90 mg initially and 4 wk later, then 90 mg q 12 wk.

Availability

Solution for subcutaneous injection: 45 mg/0.45 mL in single-use vials and prefilled syringes, 90 mg/mL in single-use vials and prefilled syringesvial

Nursing implications

Nursing assessment

  • Assess affected area(s) prior to and periodically during therapy.
  • Assess for signs of infection (fever, dyspnea, flu-like symptoms, frequent or painful urination, redness or swelling at the site of a wound), including tuberculosis, prior to injection. Ustekinumab is contraindicated in patients with active infection. New infections should be monitored closely; most common are upper respiratory tract infections, bronchitis, and urinary tract infections. Infections may be fatal, especially in patients taking immunosuppressive therapy. genetic implication Patients genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections; diagnostic testing should be considered.
  • Assess patient for latent tuberculosis with a tuberculin skin test prior to initiation of therapy. Treatment of latent tuberculosis should be started before therapy with ustekinumab.
  • Monitor for signs and symptoms of hypersensitivity reaction and anaphylaxis (rash, chest tightness, feeling faint, difficulty breathing, throat tightness, swelling of face, eyelids, tongue, or throat) during therapy.

Potential Nursing Diagnoses

Impaired skin integrity (Indications)

Implementation

  • Administer a tuberculin skin test prior to administration of ustekinumab. Patients with active latent TB should be treated for TB prior to therapy.
    • Immunizations should be current prior to initiating therapy. Patients on ustekinumab may receive concurrent vaccinations, except for live vaccines.
  • Subcutaneous: Administer using a 27 gauge, 1/2 inch needle in upper arm, gluteal region, thigh, or abdomen; rotate site. Do not administer in areas that are tender, bruised, erythematous, or indurated. Solution is colorless to light yellow and may contain a few small translucent or white particles; do not administer solutions that are discolored, cloudy, or contain other particulate matter. Do not shake. Store solution in refrigerator; do not freeze.

Patient/Family Teaching

  • Instruct patient on correct technique for self-injection, care and disposal of equipment. Review Medication Guide with patient before starting therapy and with each injection.
  • Inform patient that ustekinumab may lower ability to fight and increase risk for infections. Advise patient to notify health care professional immediately if signs of anaphylaxis or infection (fever, sweats, chills, muscle aches, cough, shortness of breath, blood in phlegm, weight loss, warm, red, or painful sores, diarrhea or stomach pain, burning or urination or urinary frequency, tiredness) occur.
  • Inform patient that ustekinumab may increase for cancer. Advise patient to obtain preventative screening.
  • Advise patient to notify health care professional if signs of reversible posterior leukiencephalopathy syndrome (headache, seizures, confusion, visual problems) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Instruct patient to notify health care professional of medication regimen prior to treatment or surgery.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • Decrease in extent and severity of psoriatic lesions.
  • Decreased progression of psoriatic arthritis
References in periodicals archive ?
SAN DIEGO -- A 12-week course of ustekinumab significantly reduced inflammation in the aorta--an effect on par with the benefit of statins--in patients with moderate to severe plaque psoriasis.
The NAVIGATE trial evaluated patients who did not achieve a response of cleared or minimal disease, an Investigator's Global Assessment (IGA) score of 0 or 1, by week 16 when treated with Stelara (ustekinumab), and were then randomised to either switch to guselkumab or continue on ustekinumab.
The researchers looked at the medical histories of patients with moderate to severe psoriasis enrolled in one phase II and two phase III trials of ustekinumab. The patients were enrolled in either the phase II C0379T04 trial (320), the phase III PHOENIX II trial (766), or the phase III PHOENIX III trial (1,230).
Novartis, a global leader in immuno-dermatology and rheumatology, announced additional results from the head-to-head CLARITY study demonstrating the superiority of Cosentyx (secukinumab) compared to Stelara (ustekinumab) in delivering specific quality of life (QoL) aspects in adults with moderate-to-severe plaque psoriasis at 16 weeks.
(6) Ustekinumab, an IL-23 inhibitor, targets the shared p40 subunit of the 1L-12 and IL-23 cytokines.
From the Bioceros platform, the company will expand with the addition of three preclinical product candidates: BOW080, a proposed biosimilar to eculizumab (reference biologic Soliris); BOW090, a proposed biosimilar to ustekinumab (reference biologic STELARA); and BOW100, a proposed biosimilar to golimumab (reference biologic SIMPONI).
More than two thirds of patients with moderate to severe plaque psoriasis achieved at least a 75% reduction in area and severity after just two subcutaneous doses of ustekinumab, according to phase III study results presented at the 21st meeting of the World Congress of Dermatology.
Investigators will highlight risankizumab response over time across various psoriasis patient subgroups in the first integrated efficacy analyses of ultIMMa-1 and ultIMMa-2, two replicate trials comparing risankizumab to STELARA (ustekinumab) or placebo.
GENEVA -- Ixekizumab improved fingernail psoriasis significantly faster and with a higher complete nail clearance rate by week 24, compared with ustekinumab, in a head-to-head phase 3b randomized trial, Yves Dutronc, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
M2 PHARMA-November 8, 2017-Janssen announces primary endpoint from Phase 2 study of STELARA (ustekinumab) in lupus patients
At the 210 mg dose, brodalumab was shown to be efficacious in total skin clearance of psoriasis compared to placebo and superior to ustekinumab at week 12 in two replicate comparator trials involving 3,500 patients, concluded the company.
The CHMP positive opinion is supported by data from the global Phase 3 psoriasis program evaluating more than 2,000 patients with moderate to severe plaque psoriasis across four pivotal Phase 3 studies.1-3 Across all four studies, ultIMMA-1, ultIMMa-2, IMMhance and IMMvent, all co-primary and ranked secondary endpoints were met, achieving a significantly higher response of clear or almost clear skin (Static Physicians Global Assessment sPGA 0/1 and Psoriasis Area and Severity Index PASI 90) compared to ustekinumab, adalimumab and placebo at week 16 and up to week 52 (depending on study design).1-3 The most frequently reported adverse reactions were upper respiratory infections, which occurred in 13 percent of patients.5 Most reported adverse reactions were mild or moderate in severity.5