ustekinumab (GI indication)
Brand: Stelara
Prototype: ustekinumab
Drug Class: IL-12/IL-23 inhibitor (monoclonal antibody)
Drug Family: biologic
Subclass: anti-p40 subunit antibody
Organ Systems: gastrointestinalimmunology
Mechanism of Action
Human monoclonal antibody that binds the shared p40 subunit of IL-12 and IL-23, preventing these cytokines from binding to their receptors on T-cells and natural killer cells. This inhibits Th1 and Th17-mediated inflammatory responses important in IBD pathogenesis.
p40 subunit shared by IL-12 and IL-23
Indications
- moderate to severely active Crohn's disease
- moderate to severely active ulcerative colitis
- plaque psoriasis
- psoriatic arthritis
Contraindications
- active clinically important infection
- hypersensitivity to ustekinumab
Adverse Effects
Common
- nasopharyngitis
- upper respiratory infection
- headache
- injection site reactions
Serious
- serious infections
- reversible posterior leukoencephalopathy syndrome (RPLS — rare)
- malignancy
Pharmacokinetics (ADME)
| Absorption | IV induction dose (weight-based); SC maintenance doses every 8–12 weeks |
| Distribution | Vd ~4.6 L; primarily intravascular |
| Metabolism | proteolytic catabolism |
| Excretion | proteolytic degradation |
| Half-life | ~14.9–45.6 days |
| Onset | weeks (IBD response in 8 weeks) |
| Peak | end of infusion (IV) or 7–13 days (SC) |
| Duration | weeks (maintenance SC dosing) |
| Protein Binding | not applicable |
| Vd | 4.6 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| live vaccines | immunosuppression increases risk of live vaccine infection | major |
| CYP450 substrates | normalization of CYP450 activity as inflammation resolves may alter drug levels | minor |
Nursing Considerations
- For Crohn's and UC induction: single weight-based IV dose (260–520 mg depending on weight); then SC 90 mg every 8–12 weeks for maintenance.
- Screen for TB, viral hepatitis B/C, and other infections before initiating; update immunizations including live vaccines before starting.
- Monitor for signs of infection throughout therapy; hold treatment and evaluate for serious infection before resuming.
- Educate patients about injection technique for self-administered SC doses; proper storage at 2–8°C required.
Clinical Pearls
- Ustekinumab has a favorable safety profile compared to TNF inhibitors, with lower rates of opportunistic infections and no increase in major cardiovascular events — making it preferred in patients with prior TB exposure or recurrent infections.
- By targeting the upstream p40 subunit shared by both IL-12 and IL-23, ustekinumab blocks both Th1 and Th17 pathways simultaneously, addressing multiple inflammatory axes in IBD.
Safety Profile
Pregnancy avoid
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.