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 ?
North Chicago, Illinois-based global biopharmaceutical company AbbVie (NYSE: ABBV) has presented positive results from the Phase 3 ultIMMa-1 and ultIMMa-2 replicate clinical trials that evaluated the safety and efficacy of risankizumab (150 mg) compared to placebo or ustekinumab at the 2018 American Academy of Dermatology annual meeting, the company said.
GENEVA -- The risk of developing on-treatment nonmelanoma skin cancer (NMSC) was lower among patients on the interleukin-12-/23 inhibitor ustekinumab (Stelara) and those on the three tumor necrosis factor (TNF) inhibitors included in the PSOLAR registry, compared with psoriasis patients on methotrexate, according to a new analysis of the registry data.
The guselkumab group patients achieved an IGA score of 0 or one and at least a two-grade improvement from week 28 through week 40, compared to the ustekinumab group.
After nine months, 69% of patients maintained clear or almost clear skin with BI 655066 in the higher dose group compared to 30% of patients on ustekinumab.
Updated recommendations from GRAPPA include new data regarding ustekinumab, apremilast, and secukinumab, as well as data on comorbidities (J Rheumatol.
From the Bioceros platform, Epirus will expand its pipeline 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).
There are currently eight registered biologic drugs in South Africa (SA), of which four are tumour necrosis factor alpha inhibitors (TNFi) and four are non-TNFi, including ustekinumab, which is currently registered for the treatment of psoriasis but not for the arthritides (Table 1).
Ustekinumab is an IL-12/23 inhibitor that blocks the activity of IL12 and IL23 by binding to their p40 subunit.
For example, a clinical trial involving 1,230 psoriasis patients randomized to ustekinumab or placebo showed that at baseline 27% of subjects had clinically significant depression based upon the Hospital Anxiety and Depression Scale (HADS).
An international team of scientists randomly assigned 526 Crohn's patients who had failed to improve with standard medications to get an injection of ustekinumab or a placebo shot.
The biologic treatments etanercept (Enbrel), adalimumab (Humira), inflixirnab (Remicade), and ustekinumab (Stelara), which are all category B drugs, could interfere with normal embryonic development and affect fetal and newborn immunity However, there are numerous pregnancy registries for both psoriasis and other inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and ulcerative colitis, which show that biologics have had no long-term implications for the normal development of the infant immune system.
A recent head-to-head trial compared the efficacy and safety of ustekinumab with etanercept and found superior efficacy with ustekinumab, with comparable adverse events.