Introduction
Stelara (ustekinumab) is a human monoclonal antibody biologic medication developed by Janssen Pharmaceuticals. It represents a novel therapeutic approach for several immune-mediated inflammatory conditions by targeting specific cytokines involved in the inflammatory cascade. First approved by the FDA in 2009, Stelara has become an important treatment option for patients with moderate to severe plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis.
Mechanism of Action
Stelara exerts its therapeutic effects through targeted inhibition of interleukin-12 (IL-12) and interleukin-23 (IL-23), two key cytokines involved in inflammatory and immune responses. Ustekinumab binds with high specificity and affinity to the p40 protein subunit common to both IL-12 and IL-23 cytokines, preventing their interaction with cell surface receptors on T cells, natural killer cells, and antigen-presenting cells. This inhibition disrupts the IL-12 and IL-23 mediated signaling pathways, including the Th1 and Th17 cell differentiation and cytokine cascades, which are implicated in the pathogenesis of several autoimmune and inflammatory conditions.
Indications
FDA-approved indications for Stelara include:
- Moderate to severe plaque psoriasis in adults and pediatric patients (6 years and older) who are candidates for phototherapy or systemic therapy
- Active psoriatic arthritis in adults (as monotherapy or in combination with methotrexate)
- Moderately to severely active Crohn's disease in adults
- Moderately to severely active ulcerative colitis in adults
Dosage and Administration
Initial Dosing:- Plaque Psoriasis: 45 mg for patients ≤100 kg; 90 mg for patients >100 kg administered subcutaneously at weeks 0, 4, and then every 12 weeks
- Psoriatic Arthritis: 45 mg administered subcutaneously at weeks 0, 4, and then every 12 weeks
- Crohn's Disease: Single IV infusion based on weight (approximately 6 mg/kg) followed by 90 mg subcutaneously at week 8, then every 8 weeks
- Ulcerative Colitis: Single IV infusion based on weight (approximately 6 mg/kg) followed by 90 mg subcutaneously at week 8, then every 8 weeks
- Renal Impairment: No dosage adjustment necessary
- Hepatic Impairment: No dosage adjustment necessary
- Elderly: No specific dosage adjustment recommended
- Pediatric: For plaque psoriasis in patients 6 years and older, dosing based on weight
Pharmacokinetics
Absorption: Bioavailability following subcutaneous administration is approximately 57% Distribution: Volume of distribution is 1.7-2.1 L, suggesting primarily vascular distribution Metabolism: Expected to be degraded into small peptides and amino acids via catabolic pathways Elimination: Half-life is approximately 15-32 days; clearance is 1.99-2.22 L/day Time to Peak Concentration: 7-13.5 days after subcutaneous administrationContraindications
- History of serious hypersensitivity reaction to ustekinumab or any excipients
- Clinically important active infection
- Patients with active tuberculosis (must be treated prior to initiating Stelara)
Warnings and Precautions
Infections: Increased risk of serious infections requiring hospitalization; opportunistic infections may occur Malignancy: Theoretical risk of malignancy with immunosuppressive therapies Hypersensitivity Reactions: Anaphylaxis and angioedema have been reported Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Rare cases reported Immunizations: Avoid live vaccines during treatment; ensure all vaccinations are current before initiation Tuberculosis: Evaluate for latent TB before initiating treatmentDrug Interactions
Live Vaccines: Avoid concurrent administration CYP450 Substrates: May normalize formation of CYP450 enzymes, potentially affecting drugs metabolized by these enzymes Other Biologics: Increased risk of infections when combined with other immunosuppressive agents Therapeutic Drug Monitoring: Limited data on interactions with conventional DMARDsAdverse Effects
Most Common (≥10%): Nasopharyngitis, upper respiratory tract infection, headache, fatigue Serious Adverse Effects:- Serious infections (1.0-1.2%)
- Malignancies (0.2-0.3%)
- Hypersensitivity reactions
- Reversible posterior leukoencephalopathy syndrome
- Cardiovascular events
Monitoring Parameters
Baseline:- Complete blood count with differential
- Liver function tests
- Renal function tests
- Tuberculosis screening (PPD or interferon-gamma release assay)
- Hepatitis B and C screening
- Pregnancy test if applicable
- Signs and symptoms of infection at every visit
- Clinical response assessment
- Injection site reactions
- Periodic monitoring of CBC, LFTs
- Annual tuberculosis screening in high-risk patients
- Monitoring for signs of malignancy
Patient Education
Administration:- Proper technique for subcutaneous injection if self-administering
- Rotation of injection sites (thighs, abdomen, upper arms)
- Storage requirements (refrigeration at 2-8°C)
- Report any signs of infection (fever, cough, flu-like symptoms)
- Seek immediate medical attention for allergic reactions
- Inform all healthcare providers about Stelara use
- Avoid live vaccines during treatment
- Discuss family planning if considering pregnancy
- Maintain regular follow-up appointments
- Practice good hygiene to reduce infection risk
- Report any new or worsening symptoms promptly
References
1. FDA Prescribing Information: Stelara (ustekinumab). Revised 2020. 2. Papp KA, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008;371(9625):1665-1674. 3. McInnes IB, 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(9894):780-789. 4. Feagan BG, et al. Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. N Engl J Med. 2016;375(20):1946-1960. 5. Sands BE, et al. Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2019;381(13):1201-1214. 6. Langley RG, et al. Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up. Br J Dermatol. 2015;172(5):1371-1383.