Introduction
Wezlana (ustekinumab-ttwe) is a biosimilar to Stelara (ustekinumab), approved by the FDA in October 2023. It is a human monoclonal antibody that targets interleukin-12 (IL-12) and interleukin-23 (IL-23), key cytokines involved in inflammatory and immune responses. Wezlana is indicated for several autoimmune conditions and represents a more cost-effective alternative to the reference product while maintaining equivalent safety and efficacy profiles.
Mechanism of Action
Wezlana binds with high specificity and affinity to the p40 protein subunit shared by both IL-12 and IL-23 cytokines. By inhibiting the interaction of these interleukins with their cell surface receptors, Wezlana prevents:
- T-cell activation and differentiation
- NK cell activation
- Production of pro-inflammatory cytokines (IFN-γ, IL-17, IL-22)
This immunomodulatory action reduces the inflammatory processes underlying several autoimmune conditions.
Indications
FDA-approved indications include:
- Moderate to severe plaque psoriasis in adults and pediatric patients (6 years and older)
- Active psoriatic arthritis in adults
- Moderate to severe Crohn's disease in adults
- Moderate to severe ulcerative colitis in adults
Dosage and Administration
Initial dosing:- Psoriasis: 45 mg (≤100 kg) or 90 mg (>100 kg) SC at weeks 0, 4, then every 12 weeks
- Psoriatic arthritis: 45 mg SC at weeks 0, 4, then every 12 weeks
- Crohn's disease/Ulcerative colitis: Weight-based IV infusion (~6 mg/kg) at week 0, then 90 mg SC at week 8, then every 8-12 weeks
- Subcutaneous injection in abdomen, thighs, or upper arms
- Rotate injection sites
- Allow to reach room temperature (30 minutes) before injection
- Avoid areas of psoriasis or tenderness
- Renal/hepatic impairment: No dosage adjustment required
- Elderly: Use caution; limited data in patients >65 years
- Pediatrics: Approved for psoriasis in children ≥6 years
Pharmacokinetics
Absorption: Bioavailability ~57% following SC administration Distribution: Volume of distribution ~1.7-2.1 L; low tissue penetration Metabolism: Degraded via proteolytic enzymes into small peptides and amino acids Elimination: Half-life ~15-45 days; clearance ~0.19 L/day Steady-state: Achieved by 28 weeks with every-12-week dosingContraindications
- Hypersensitivity to ustekinumab or any excipients
- Active clinically important infection
- Untreated latent tuberculosis
Warnings and Precautions
Infections: Increased risk of serious infections; hold during active infection Malignancy: Theoretical risk of malignancies; monitor for skin cancers Hypersensitivity: Anaphylaxis and angioedema reported TB reactivation: Evaluate for latent TB before initiation Vaccinations: Avoid live vaccines during treatment Reversible posterior leukoencephalopathy syndrome (RPLS): Rare neurologic events reportedDrug Interactions
- Live vaccines: Contraindicated (increased infection risk)
- CYP450 substrates: May affect metabolism of drugs with narrow therapeutic index
- Other biologics: Increased risk of immunosuppression; generally avoid combination
- TNF blockers: Increased infection risk; not recommended
Adverse Effects
Common (≥1%):- Upper respiratory infections (27%)
- Headache (15%)
- Fatigue (7%)
- Injection site reactions (6%)
- Arthralgia (5%)
- Serious infections (1.5%)
- Malignancies (0.3%)
- Hypersensitivity reactions
- Reversible posterior leukoencephalopathy syndrome
Monitoring Parameters
Baseline:- CBC with differential
- TB screening (quantiferon or PPD)
- Hepatitis B/C screening
- Pregnancy test if indicated
- Complete medical history including malignancy risk
- Signs/symptoms of infection at each visit
- Skin examination for new malignancies annually
- Clinical response assessment
- Injection site reactions
- Patient-reported outcomes
- Liver function tests (if clinically indicated)
- Inflammatory markers (CRP, ESR) for inflammatory bowel disease
Patient Education
- Self-injection technique training if appropriate
- Recognize signs of infection (fever, chills, cough)
- Report any neurological symptoms immediately
- Avoid live vaccines during treatment
- Inform all healthcare providers about Wezlana use
- Proper storage (refrigerate at 2-8°C; do not freeze)
- Dispose of needles/syringes in sharps container
- Importance of adherence to dosing schedule
- Pregnancy planning: Discuss with provider before conception
References
1. FDA Approval Letter: Wezlana (ustekinumab-ttwe). October 2023 2. Biosimilar Biological Product Licensing Applications for Wezlana. FDA Clinical Review 3. Reich K, et al. Efficacy and safety of ustekinumab biosimilars: systematic review. J Eur Acad Dermatol Venereol. 2023 4. Sandborn WJ, et al. Ustekinumab induction and maintenance therapy in refractory Crohn's disease. N Engl J Med. 2012 5. Clinical Pharmacology and Biopharmaceutics Review(s). FDA Application Number: 761356 6. Wezlana Prescribing Information. Amgen Inc. 2023 7. Biosimilars in rheumatology: current perspectives and future considerations. Nat Rev Rheumatol. 2022 8. FDA Briefing Document: Arthritis Advisory Committee Meeting. September 2023
This monograph is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for medical guidance.