What is ustekinumab and why is it effective in PsA?
Ustekinumab (Stelara) is a human IgG1κ monoclonal antibody that binds to the p40 subunit of both IL-12 and IL-23 preventing their binding to their shared cell surface receptor chain, IL-12β. The inhibition of IL-12 signaling abrogates Th1 response with reduction in TNF-α, IFN-γ, and IL-2 production. The inhibition of IL-23 signaling abrogates Th17 response with reduction in IL-6, IL-17, IL-21, IL-22, and TNF-α production. Th17 cells and IL-23 production by DCs and keratinocytes are important in the pathogenesis of psoriasis. Half-life is 15 to 45 days.
- • Available formulation: single-use 45-mg and 90-mg prefilled syringes. A 45-mg single-dose vial for SC administration and a 130-mg single-dose vial for IV administration (Crohn’s disease) are also available.
- • FDA-approved indications: psoriasis (age >12 years), PsA (adults), Crohn’s disease (adults). Although not FDA-approved, it has been used with success in patients with AS.
- • Adult psoriasis and PsA dosage: patient ≤100 kg: 45 mg SC initially, followed by 45 mg in 4 weeks, then 45 mg every 12 weeks. Dosage for >100 kg: 90 mg SC initially, followed by 90 mg in 4 weeks, then 90 mg every 12 weeks. Can be combined with a csDMARD (e.g., MTX).
- • Monitoring: routine monitoring for other csDMARDs (MTX).
- • Adverse reactions: nasopharyngitis (10%), nonmelanoma skin cancers.
- • Serious infections (2%–3%): IL-12/IL-23 are important for resistance against mycobacterial and salmonella infections. IL-17 is important for resistance against fungal infections.
- • Precautions: do not use in patients with active infection. Do not combine with other biologics.