Ustekinumab (Stelara) is a human monoclonal antibody that binds to and interferes with the proinflammatory cytokines, interleukin (IL)-12 and IL-23.

• Crohn disease:

  • It is used in the treatment of moderately to severely active Crohn disease in adults who have failed or were intolerant to immunomodulatory or corticosteroid therapy, but never failed tumor necrosis factor (TNF) inhibitor therapy or who were intolerant or have failed treatment with one or more TNF blockers.

• Plaque psoriasis:

  • It is used in the treatment of moderate to severe plaque psoriasis in patients ≥12 years of age who are candidates for phototherapy or systemic therapy

• Psoriatic arthritis:

  • It is used in the  treatment of active psoriatic arthritis (as monotherapy or in combination with methotrexate) in adults

Stelara (Ustekinumab) dose in Adults

Stelara (Ustekinumab) dose in the treatment of Crohn disease:

• Induction: intravenous:

  • ≤55 kg:

    • 260 mg given as a single dose

  • >55 kg to 85 kg:

    • 390 mg given as a single dose

  • >85 kg:

    • 520 mg given as a single dose

• Maintenance: SubQ:

  • 90 mg given every 8 weeks
  • begin maintenance dosing 8 weeks after the intravenous induction dose.

Stelara (Ustekinumab) dose in the treatment of Plaque psoriasis: SubQ:

• Initial and maintenance:

  • ≤100 kg:

    • 45 mg given at 0 and 4 weeks, and then every 12 weeks thereafter

  • >100 kg:

    • 90 mg given at 0 and 4 weeks, and then every 12 weeks thereafter.

Stelara (Ustekinumab) dose in the treatment of Psoriatic arthritis: SubQ:

• Initial and maintenance:
  • 45 mg given at 0 and 4 weeks, and then every 12 weeks thereafter.

Stelara (Ustekinumab) dose in the treatment of Coexistent psoriatic arthritis and moderate to severe plaque psoriasis in patients >100 kg:

• Initial and maintenance:
  • 90 mg given at 0 and 4 weeks, and then every 12 weeks thereafter.

Stelara (Ustekinumab) Dose in Childrens

Stelara (Ustekinumab) dose in the treatment of Plaque psoriasis:

• Children ≥12 years and Adolescents: SubQ:

  • <60 kg:

    • 75 mg/kg given at 0 and 4 weeks, and then every 12 weeks thereafter

  • ≥60 kg to ≤100 kg:

    • 45 mg given at 0 and 4 weeks, and then every 12 weeks thereafter

  • >100 kg:

    • 90 mg given at 0 and 4 weeks, and then every 12 weeks thereafter

Stelara (Ustekinumab) pregnancy Risk Category: C

• Animal reproduction studies have not shown adverse events; human pregnancy data are very limited.
• Plaque psoriasis is a condition that affects pregnant women. It is generally better to use other agents.

Ustekinumab use during breastfeeding:

• It is unknown if ustekinumab can be found in breast milk.
• Systemic exposure to breastfed infants is unlikely due to the large size and degradation of ustekinumab in the GI tract.
• According to the manufacturer the decision to stop or continue breastfeeding during therapy must consider the risks to infants, the benefits to the mother, and the benefits to the mother.

Stelara (Ustekinumab) dose in kidney disease:

• There are no dosage adjustments given in the manufacturer's labeling (has not been studied).

Stelara (Ustekinumab) dose in liver disease:

• There are no dosage adjustments given in the manufacturer's labeling (has not been studied).

Common Side Effects of Ustekinumab (Stelara):

• Immunologic:

  • Antibody development

• Infection:

  • Infection

• Respiratory:

  • Nasopharyngitis

Less Common Side Effects of Ustekinumab (Stelara):

• Central Nervous System:

  • Headache
  • Fatigue
  • Dizziness
  • Depression

• Dermatologic:

  • Pruritus
  • Acne Vulgaris

• Gastrointestinal:

  • Vomiting
  • Nausea
  • Dental Disease

• Genitourinary:

  • Vaginal Mycosis
  • Vulvovaginal Candidiasis
  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Skin Carcinoma

• Local:

  • Erythema At Injection Site

• Neuromuscular & Skeletal:

  • Arthralgia
  • Back Pain
  • Asthenia

• Respiratory:

  • Bronchitis
  • Sinusitis
  • Pharyngolaryngeal Pain

Rare side effects of Stelara (ustekinumab):

• Gastrointestinal:

  • Appendicitis
  • Cholecystitis
  • Gastroenteritis

• Genitourinary:

  • Perirectal Abscess

• Infection:

  • Sepsis
  • Viral Infection

• Neuromuscular & Skeletal:

  • Osteomyelitis

• Respiratory:

  • Pneumonia

Contraindications to Ustekinumab (Stelara):

• Clinically significant hypersensitivity to ustekinumab and any component of the formulation
• Severe infections such as sepsis, tuberculosis, and opportunistic infections

Warnings and precautions

• Formation of antibodies:
  • Therapy has shown anti-bodies to ustekinumab.
• Hypersensitivity reactions
  • Hypersensitivity has been observed, which includes anaphylaxis or angioedema.
  • Stop immediately if you notice signs/symptoms that indicate hypersensitivity reaction. Treat the situation as soon as possible.
• Infections
  • This can increase the chance of infection or reactivate latent infections.
  • Use of the product has been associated with serious bacterial, fungal and viral infections.
  • Patients with a clinically significant active infection should be avoided until the infection is resolved or successfully treated.
  • Patients with a history or recurrent infection, conditions that may make them more susceptible to infection (eg diabetes, residence/travel from areas with endemic mycoses), chronic, localized, or latent infections or genetic deficiency in IL-12/IL23 (IL-12/IL23 genetic deficiency) could be at risk of disseminated infections.
  • Patients who get a new infection during treatment should inform their doctor and be closely monitored.
  • The patient should not be treated if they have a serious infection.
• Malignancy
  • Although it can increase the chance of developing malignancy, the effects on their course and development are not completely understood.
  • Patients who received ustekinumab were at high risk of developing nonmelanoma-related skin cancers have seen cutaneous squamous cells carcinomas (multiple) that appeared quickly.
  • Patients should be closely watched for nonmelanoma-related skin cancers.
  • Patients over 60 years old, who have had prolonged immunosuppression in the past, or patients who have received PUVA treatment, should be closely monitored.
  • Patients with a history or malignancy should be cautious about taking the drug (not recommended for this population).
• Neurotoxicity:
  • Rarely seen, reversible posterior leukoencephalopathy (RPLS), can sometimes be fatal.
  • Symptoms include confusion, headaches, seizures, and visual disorders.
  • Monitor your patient for signs and symptoms of RPLS. If symptoms persist, discontinue therapy and provide appropriate therapy.
• Noninfectious pneumonia:
  • There have been cases of interstitial pneumonia, cryptogenic organizing pneumonia and eosinophilic bronchitis.
  • You may experience symptoms such as cough, dyspnea and interstitial infections.
  • If you suspect or confirm non-infectious pneumonia, stop treatment and get the appropriate treatment.
• Tuberculosis
  • Patients with active tuberculosis should not be given this medication.
  • Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test before starting therapy.
  • Before ustekinumab is administered, it is important to treat latent TB.
  • In patients with a history of latent or active tuberculosis, treatment with ATT may be considered if adequate treatment can not be confirmed.
  • Patients should be closely monitored for TB reactivation during and after treatment.

Ustekinumab: Drug Interaction

Monitor:

• Tuberculosis screening (prior to initiating and periodically during therapy)
• CBC
• ustekinumab-antibody formation
• monitor for signs/symptoms of infection
• reversible posterior leukoencephalopathy syndrome (RPLS)
• squamous cell skin carcinoma.

How to administer Ustekinumab (Stelara)?

Intravenous injection:

• Infuse intravenously over at least 60 minutes
• use of an intravenous set with an in-line, low-protein binding filter (0.2 micrometers) required.
• It should not be infused with other medications in the same intravenous line.

Subcutaneous injection:

• Administer by subcutaneous injection into the top of the thigh, abdomen, upper arms, or buttocks.
• Rotate sites.
• Injection into tender, erythematous, bruised or indurated skin should be avoided.
• Avoid areas of skin where psoriasis is present.
• Discard any unused portion.
• It is intended for use under the supervision of a physician; self-injection after proper training may be allowed.

Mechanism of action of Ustekinumab (Stelara):

• Ustekinumab, a monoclonal human antibody, is available.
• It binds and interferes with proinflammatory cytokines, interleukin (12 and IL-23).
• IL-12/IL-23 can have biological effects such as natural killer (NK), cell activation, CD4+T-cell differentiation and activation.
• Ustekinumab can also cause interference with the expression of monocyte chemotactic proteins-1 (MCP-1), tumour necrosis factor alpha (TNF–a), interferon inducible protein-10(IP-10), and Interleukin-8 (8 (IL-8).
• A reduction in proinflammatory signals is associated with significant clinical improvement in patients suffering from psoriasis or psoriatic arthritis.

Half-life elimination:

• 10 to 126 days
• Psoriasis: 14.9 ± 4.6 to 45.6 ± 80.2 days
• Crohn disease: ~19 days

Time to peak, plasma:

• 45 mg: 13.5 days
• 90 mg: 7 days

International Brands of Ustekinumab:

• Stelara

Ustekinumab Brand Names in Pakistan:

No Brands Available in Pakistan.