STELARA
Clinical safety rating: caution
Ustekinumab (Stelara) is a human monoclonal antibody targeting the p40 subunit of IL-12 and IL-23, indicated for moderate-to-severe plaque psoriasis, active psoriatic arthritis, moderately to severely active Crohn’s disease, and moderately to severely active ulcerative colitis. It offers a convenient subcutaneous maintenance dosing schedule (every 8–12 weeks) and may be used as first-line biologic therapy in appropriate patients.
Ustekinumab is a human IgG1κ monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit of human interleukin (IL)-12 and IL-23, thereby blocking IL-12 and IL-23 mediated cell signaling and cytokine cascades.
| Metabolism | Ustekinumab is a monoclonal antibody; metabolism is via catabolism into small peptides and amino acids. No significant involvement of CYP450 enzymes. |
| Excretion | Primarily degraded into small peptides and individual amino acids; no significant renal or biliary excretion of intact antibody. Fecal excretion of degradation products is negligible. |
| Half-life | Terminal elimination half-life of approximately 3 weeks (range 15–32 days) in patients with psoriasis; supports subcutaneous dosing every 12 weeks. |
| Protein binding | Ustekinumab is a monoclonal antibody; binding to plasma proteins is negligible (less than 1%). |
| Volume of Distribution | Volume of distribution approximately 0.08–0.16 L/kg, indicating limited extravascular distribution. |
| Bioavailability | Subcutaneous: approximately 57% (range 45–68%) relative to intravenous administration. |
| Onset of Action | Subcutaneous: Clinical improvement may be observed within 2–4 weeks; maximal effect usually achieved by 12–24 weeks. |
| Duration of Action | Duration of clinical effect: 8–12 weeks after a single subcutaneous dose; repeated dosing every 12 weeks maintains efficacy. |
Plaque psoriasis/Psoriatic arthritis: 45 mg subcutaneously (SC) for patients ≤100 kg or 90 mg SC for patients >100 kg at Weeks 0 and 4, then every 12 weeks. Crohn’s disease/Ulcerative colitis: Weight-based single intravenous induction dose (~6 mg/kg) at Week 0, followed by 90 mg SC at Week 8 and every 8 weeks thereafter.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required. Ustekinumab clearance is not affected by renal function; formal studies in renal impairment have not been performed. |
| Liver impairment | No dose adjustment provided in labeling. Use with caution in severe hepatic impairment (Child-Pugh C) as no specific studies have been conducted. |
| Pediatric use | Pediatric plaque psoriasis and psoriatic arthritis (≥6 years): Weight-based SC dosing – patients <60 kg: 0.75 mg/kg, patients 60–100 kg: 45 mg, patients >100 kg: 90 mg; administered at Weeks 0 and 4, then every 12 weeks. Safety and efficacy in pediatric Crohn’s disease or ulcerative colitis have not been established. |
| Geriatric use | No dose adjustment based on age alone. Elderly patients may be at increased risk of infections; use with caution. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Limited human data are available. Animal reproduction studies did not show adverse developmental effects. Ustekinumab should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consider the risk of fetal infection if the infant is exposed to ustekinumab in utero.
| Placental transfer | As an IgG1 antibody, ustekinumab is expected to cross the placental barrier, particularly during the third trimester. Cord blood concentrations at delivery may exceed maternal levels. |
| Breastfeeding | Not known if excreted in human milk; human IgG present in milk. Likely low systemic exposure in infant. M/P ratio not established. Weigh benefits vs risks. |
■ FDA Black Box Warning
STELARA may increase the risk of infections, including tuberculosis. Serious infections have been reported. Test for TB prior to initiating therapy; monitor for signs of infection during and after treatment.
| Common Effects | Nasopharyngitis, Upper respiratory tract infection, Headache, Fatigue, Injection site reactions (erythema, pain, pruritus), Arthralgia, Back pain, Diarrhea, Pruritus |
| Serious Effects | Serious infections (e.g., tuberculosis, sepsis, pneumonia), malignancies (e.g., non-melanoma skin cancer), anaphylaxis/hypersensitivity, posterior reversible encephalopathy syndrome (PRES), non-infectious pneumonia. |
["Clinically significant hypersensitivity to ustekinumab or any excipients","Active serious infections (e.g., active tuberculosis)"]
| Precautions | ["Increased risk of infections (including active tuberculosis, invasive fungal infections, and opportunistic infections)","Reactivation of latent tuberculosis (perform TB screening prior to initiation)","Serious allergic reactions (angioedema, anaphylaxis)","Malignancy risk (especially in patients with risk factors)","Non-infectious pneumonia (cases of interstitial pneumonia, eosinophilic pneumonia)","Cardiovascular events (including myocardial infarction and stroke) in patients with psoriatic arthritis","Exacerbation of inflammatory bowel disease (when used for psoriasis/psoriatic arthritis)"] |
Loading safety data…
| Teratogenic Risk | No adequate well-controlled studies in pregnant women. IgG1 monoclonal antibodies cross placenta; highest transfer in third trimester. Animal studies not suggestive of teratogenicity. Theoretical risk of immune suppression in neonate. |
| Fetal Monitoring | Monitor for infections in mother; in infant after birth, monitor for live vaccine response and opportunistic infections. |
| Fertility Effects | No data on fertility in humans; animal studies no adverse effects on male or female fertility. |