Generic Name

Ustekinumab

Mechanism

Ustekinumab is a humanized IgG1κ monoclonal antibody that selectively binds the p40 subunit shared by interleukin‑12 (IL‑12) and interleukin‑23 (IL‑23).
• IL‑12 drives Th1 differentiation and interferon‑γ production, driving cell‑mediated inflammation.
• IL‑23 stabilizes and expands Th17 cells, contributing to neutrophil activation and chronic inflammation.

By neutralizing both cytokines, ustekinumab disrupts the Th1/Th17 pathogenic axis, leading to diminished disease activity in psoriasis, Crohn disease, and psoriatic arthritis.

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Pharmacokinetics

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Indications

• Plaque psoriasis (moderate‑to‑severe)
• Moderate‑to‑severe Crohn disease (adult and adolescents ≥12 yrs)
• Psoriatic arthritis (active disease refractory to other systemic therapy)
• Psoriatic alopecia (off‑label, evidence emerging)

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Contraindications

• Active infections (TB, fungal, opportunistic) – screen with interferon‑γ release assay (IGRA) or PPD prior to initiation.
• Severe hypersensitivity to ustekinumab or any excipient.
• Pregnancy – category B; use only if benefits outweigh risks.
• Immunodeficiency (e.g., HIV with CD4 <200 cells/µL).
• Uncontrolled asthma or severe allergic reactions to monoclonal antibodies.

Warnings
• Increased risk of upper respiratory tract infections, nasopharyngitis.
• Rare but serious opportunistic infections (e.g., mycobacterial, fungal).
• Potential for reactivation of hepatitis B; screen for HBsAg/HBcAb.
• No evidence of malignancy risk with long‑term therapy, but monitor per guidelines.

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Dosing

Psoriasis & Psoriatic Arthritis
• *Initial dose*: 90 mg SC (half‑dose 45 mg if weight <60 kg).
• *Maintenance*: 90 mg SC every 12 weeks.
• *Rescue*: Up to 90 mg SC at week 4 if insufficient response, then follow maintenance interval.

Crohn Disease
• *Initial dose*: 6 mg/kg SC (max 90 mg) on day 1, repeat at week 4.
• *Maintenance*: 90 mg SC every 12 weeks.

*Administration technique*: Use pre‑filled syringe and needle = 25 mm depth. Rotate injection sites (abdomen, thigh, upper arm).

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Adverse Effects

Common (≥5 %)
• Upper respiratory tract infection
• Nasopharyngitis
• Arthralgia
• Headache
• Constipation

Serious (≥1 %)
• Opportunistic infections (TB, fungal, viral)
• Herpes zoster reactivation
• Sepsis / septic shock
• Severe hypersensitivity/anaphylaxis
• New‑onset or worsening inflammatory bowel disease in rare cases

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Monitoring

• Baseline: CBC, liver enzymes, renal function, hepatitis B surface antigen, HIV Ag/Ab, TB screening (IGRA/PPD).
• Periodic: CBC and CMP every 3 months; liver enzymes at least annually.
• Immunization status: Update live vaccines >4 weeks before initiation; inactivated vaccines are safe.
• Pregnancy: No pregnancy during therapy; discontinue if conception occurs.

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Clinical Pearls

1. Weight‑based vs Fixed Dose – For Crohn disease, weight‑based dosing (≤90 mg) optimizes response in >90 kg patients; however, many clinicians use 90 mg fixed for simplicity given the modest variety in response.
2. Switching from Anti‑TNF – Patients transitioning from infliximab or adalimumab to ustekinumab should schedule the first dose 2–4 weeks after last anti‑TNF infusion to reduce the risk of infusion reactions.
3. Adalimumab‑to‑Ustekinumab – Ustekinumab has a unique pharmacodynamic profile; consider 12‑week interval for moderate disease to expedite control; patients on dupilumab or vedolizumab may also shift to ustekinumab if co‑existing psoriasis.
4. Vaccination Window – Non‑live vaccines can be given any time; live vaccines must be deferred ≥4 weeks post‑dose and re‑administered only after drug discontinuation.
5. Rare Psoriatic Alopecia – Small series show >70 % scalp clearance after 6 months; consider in severe alopecia trials pending approval.

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