Usage
Ustekinumab is prescribed for the treatment of moderate to severe plaque psoriasis in adults and children 6 years and older, psoriatic arthritis in adults, Crohn’s disease in adults, and ulcerative colitis in adults. It is classified as an immunosuppressant, specifically a human monoclonal antibody. Ustekinumab works by targeting the p40 subunit of interleukin (IL)-12 and IL-23 cytokines, thereby inhibiting these pro-inflammatory cytokines crucial in the development of these conditions.
Alternate Names
Ustekinumab is marketed under various brand names including Stelara, Pyzchiva, Steqeyma, Uzprovo, and Wezenla. Pyzchiva, Steqeyma, Uzprovo, and Wezenla are biosimilars of Stelara.
How It Works
Pharmacodynamics: Ustekinumab binds to the p40 subunit shared by interleukin (IL)-12 and IL-23, effectively neutralizing their activity. This inhibits the inflammatory cascade responsible for the pathogenesis of psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis.
Pharmacokinetics: Following subcutaneous administration, ustekinumab reaches peak serum concentrations in approximately 8.5 days. It has an absolute bioavailability of 55.2%. Ustekinumab is primarily eliminated through proteolytic catabolism, similar to endogenous IgG antibodies, with negligible renal or hepatic elimination.
Mode of Action: Ustekinumab acts by preventing IL-12 and IL-23 from binding to their cell surface receptors. By blocking these cytokines, ustekinumab inhibits the activation of inflammatory cells, including T helper 1 (Th1) and Th17 cells, reducing the inflammatory response driving these diseases.
Elimination Pathways: Ustekinumab is primarily eliminated through proteolytic catabolism with negligible renal or hepatic excretion.
Dosage
Standard Dosage
Adults:
- Plaque Psoriasis and Psoriatic Arthritis: For patients weighing 100 kg or less: 45 mg subcutaneously initially and 4 weeks later, followed by 45 mg every 12 weeks. For patients weighing more than 100 kg: 90 mg subcutaneously initially and 4 weeks later, followed by 90 mg every 12 weeks.
- Crohn’s Disease and Ulcerative Colitis: Initial dose is weight-based and administered intravenously. Subsequent doses are 90 mg subcutaneously every 8 weeks, although some patients may require more frequent dosing (every 8 weeks).
Children (6-17 years, Plaque Psoriasis):
Weight-based dosing is recommended at the initial dose, 4 weeks later, then every 12 weeks thereafter.
- Less than 60 kg: 0.75 mg/kg subcutaneously.
- 60 kg or more: Adult dosing applies (45 mg subcutaneously).
Special Cases:
- Elderly Patients: No specific dose adjustment is typically necessary.
- Patients with Renal Impairment: No dose adjustment is necessary.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary.
- Patients with Comorbid Conditions: Caution should be exercised in patients with active infections.
Clinical Use Cases
Ustekinumab is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is a long-term maintenance therapy for the chronic conditions mentioned earlier.
Dosage Adjustments
Dose adjustments may be necessary based on patient response and tolerance. If a patient does not respond adequately to the standard dosing regimen, the frequency of administration may be increased.
Side Effects
Common Side Effects:
Nasopharyngitis, headache, fatigue, injection site reactions (pain, redness, swelling), upper respiratory tract infections.
Rare but Serious Side Effects:
Serious infections (bacterial, fungal, viral), including tuberculosis reactivation; allergic reactions (rash, hives, angioedema); malignancies.
Long-Term Effects:
The potential long-term effects of ustekinumab are still being studied. However, some concerns include an increased risk of certain infections and possibly malignancies with prolonged use.
Adverse Drug Reactions (ADR):
Anaphylaxis, severe infections requiring hospitalization.
Contraindications
- Hypersensitivity to ustekinumab.
- Active, clinically important infections, including active tuberculosis.
- Concomitant administration of live vaccines.
Drug Interactions
- Live vaccines: Avoid concomitant use and for a period before and after ustekinumab treatment (see specific vaccine guidelines).
- Immunosuppressants: Concurrent use can further increase the risk of infection.
- Warfarin and cyclosporine: Ustekinumab may affect the levels of these medications, necessitating monitoring and potential dose adjustments.
Pregnancy and Breastfeeding
- Pregnancy: Data on ustekinumab use during pregnancy are limited. It is advised to discuss risks and benefits with the healthcare provider. Data suggests no increased risk of congenital anomalies or pregnancy complications.
- Breastfeeding: Ustekinumab is present in breast milk in very small amounts. Due to its poor oral bioavailability, the risk to the infant is considered low. However, the decision to breastfeed while taking ustekinumab should be made in consultation with a healthcare provider.
Drug Profile Summary
- Mechanism of Action: Inhibits IL-12 and IL-23 cytokines.
- Side Effects: Nasopharyngitis, headache, fatigue, injection site reactions, infections.
- Contraindications: Hypersensitivity, active infections, live vaccines.
- Drug Interactions: Live vaccines, immunosuppressants, warfarin, cyclosporine.
- Pregnancy & Breastfeeding: Consult with a healthcare provider to weigh risks and benefits. Limited data suggest no increased risk, but caution is advised.
- Dosage: Weight-based IV loading dose followed by subcutaneous maintenance therapy every 8 or 12 weeks.
- Monitoring Parameters: Complete blood counts, liver function tests, signs and symptoms of infection.
Popular Combinations
Ustekinumab can be used with or without concomitant methotrexate for psoriatic arthritis. In some cases, other immunosuppressants may be added to enhance efficacy, but this increases the risk of infection.
Precautions
- Evaluate for tuberculosis infection before initiating therapy.
- Monitor for signs and symptoms of infection.
- Avoid live vaccines.
- Exercise caution in patients with a history of recurring infections.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ustekinumab?
A: Dosing varies depending on the indication and patient weight. For adults with plaque psoriasis and psoriatic arthritis, it is 45 mg subcutaneously every 12 weeks for those weighing 100 kg or less, and 90 mg every 12 weeks for those over 100 kg. For Crohn’s and Ulcerative colitis, the initial dose is weight-based and given intravenously, followed by 90 mg subcutaneously every 8 weeks. Pediatric dosing for plaque psoriasis is weight-based.
Q2: How is Ustekinumab administered?
A: Ustekinumab is administered via intravenous infusion for the initial dose in Crohn’s disease and ulcerative colitis, followed by subcutaneous injections for maintenance therapy for all approved indications.
Q3: What are the common side effects of Ustekinumab?
A: Common side effects include nasopharyngitis, headache, fatigue, and injection site reactions.
Q4: Can patients on Ustekinumab receive vaccinations?
A: Live vaccines should be avoided during and for a period before and after Ustekinumab treatment. Non-live vaccines are generally considered safe.
Q5: Is Ustekinumab safe during pregnancy?
A: Data is limited, but currently available information suggests no increased risk of adverse outcomes. Consult a healthcare provider to weigh the benefits and risks.
Q6: Is Ustekinumab compatible with breastfeeding?
A: Ustekinumab is present in breast milk at low levels. Due to poor oral bioavailability, the risk to infants is thought to be low. Discuss breastfeeding with a healthcare provider.
Q7: What are the contraindications for Ustekinumab?
A: Contraindications include hypersensitivity to ustekinumab, active serious infections (including tuberculosis), and concomitant use of live vaccines.
Q8: How long does it take for Ustekinumab to start working?
A: Some patients notice improvement within a few weeks, but it can take up to 6-8 weeks or longer to see significant benefit.
Q9: What monitoring is required for patients taking Ustekinumab?
A: Patients should be monitored for signs and symptoms of infection, and periodic blood tests (complete blood counts, liver function tests) are recommended.
Q10: Are there any drug interactions with Ustekinumab?
A: Ustekinumab can interact with live vaccines, immunosuppressants, warfarin, and cyclosporine.
