Instructions for Ustekinumab

1. Common name: ustekinumab, Ustekinumab

Product name:Stelara, Starano

2. Indications:

1. Psoriasis (Ps): Ustekinumab is suitable for the treatment of patients with moderate to severe plaque psoriasis aged 6 years or older who require phototherapy or systemic therapy.

2. Psoriatic arthritis (PsA): Ustekinumab is suitable for the treatment of patients 6 years or older with active psoriatic arthritis.

3. Crohn's disease (CD): Ustekinumab is suitable for the treatment of adult patients with moderately to severely active Crohn's disease.

4. Ulcerative colitis (UC): Ustekinumab is suitable for the treatment of adult patients with moderate to severe active ulcerative colitis.

3. Usage and dosage:

1. Psoriasis (Ps), psoriatic arthritis (PsA):

(1) Adult patients: For patients weighing 100 kg or less, the recommended dose of ustekinumab is 45 mg subcutaneously initially, after 4 weeks, then 45 mg every 12 weeks; for patients weighing more than 100 kg, the recommended dose is 90 mg initially, after 4 weeks, then 90 mg every 12 weeks.

(2) Pediatric patients: Ustekinumab is administered subcutaneously at weeks 0 and 4, then every 12 weeks. For patients weighing less than 60kg, the recommended dose is 0.75mg/kg; for patients weighing 60-100kg, the recommended dose is 45mg/kg; for patients weighing more than 100kg, the recommended dose is 90mg/kg.

2. Crohn's disease (CD), ulcerative colitis (UC):

(1) Intravenous injection: The adult dosage regimen of ustekinumab is based on body weight. For patients weighing less than 55kg, the recommended dose is 260mg (2 bottles); for patients weighing 55-85kg, the recommended dose is 390mg (3 bottles); for patients weighing more than 85kg, the recommended dose is 520mg (4 bottles).

(2) Subcutaneous maintenance: The recommended maintenance dose of ustekinumab is 90 mg subcutaneously administered 8 weeks after the initial intravenous dose and every 8 weeks thereafter.

3. Management:

（1) Subcutaneous injection: It is recommended that each injection of ustekinumab be performed in a different anatomical location from the previous injection (such as the upper arm, buttocks, thighs, or any quadrant of the abdomen) and not into areas of skin tenderness, abrasion, erythema, or hardening. When using single-dose vials, it is recommended to use a 1mL syringe with a 27-gauge needle. Visually inspect ustekinumab for particulate matter and discoloration. It is a colorless to pale yellow solution that may contain some small translucent or white particles. Do not use if ustekinumab is discolored or cloudy, or if other particulate matter is present.

(2) Intravenous administration: Ustekinumab must be diluted, prepared, and infused by a health care professional using sterile technique.

4. Adverse reactions:

In clinical trials, ustekinumab was well tolerated by patients, and most adverse events were mild in severity. The most common adverse reactions were headache and nasopharyngitis, and the most serious adverse reaction was severe allergic reaction. After ustekinumab was put on the market, adverse events such as allergic reactions and angioedema, rash and urticaria, opportunistic fungal infections and tuberculosis, posterior reversible encephalopathy syndrome, interstitial pneumonia, eosinophilic pneumonia and cryptogenic organizing pneumonia, pustular psoriasis, erythrodermic psoriasis, allergic vasculitis, etc. have also occurred.

5. Storage:

Vials and prefilled syringes containing ustekinumab must be refrigerated2°C to 8°C (36°F to 46°F). Store ustekinumab vials upright and keep product in original carton away from light until time of use. Do not freeze. Don't shake.

1. Subcutaneous injection of ustekinumab: If necessary, single prefilled syringes can be stored in the original carton in the dark at room temperature up to 30°C (86°F) for up to 30 days. Record the date the prefilled syringe was first removed from the refrigerator in the space provided on the carton. Syringes should not be returned to the refrigerator after being stored at room temperature. If not used within 30 days of storage at room temperature, discard syringe. Do not use ustekinumab after the expiry date on the carton or prefilled syringe.

2. Intravenous ustekinumab: If necessary, the diluted infusion solution can be stored at room temperature up to 25°C (77°F) for up to 7 hours. After preparation of the dilute solution, storage time at room temperature begins. The infusion should be completed within 8 hours after dilution in the infusion bag (the cumulative time after preparation includes the storage and infusion period). Do not freeze. Discard any unused infusion solution.

6. Taboo:

Ustekinumab is contraindicated in patients with clinically significant allergic reactions toustekinumab or any excipients.

7. Mechanism of action:

Ustekinumab is a humanIgG1曛 monoclonal antibody that specifically binds to the p40 protein subunit used by the IL-12 and IL-23 cytokines. IL-12 and IL-23 are naturally occurring cytokines involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T cell differentiation and activation. In in vitro models, ustekinumab disrupts IL-12- and IL-23-mediated signaling and cytokine cascades by disrupting the interaction of these cytokines with the shared cell surface receptor chain IL-12Rβ1. The cytokines IL-12 and IL-23 are considered important factors in chronic inflammation, a hallmark of Crohn's disease and ulcerative colitis. Genetic deletion or antibody blockade of the p40 subunit of IL-12 and IL-23 (the target of ustekinumab) showed protection in animal models of colitis.

The generic drug Ustekinumab has been launched in China and is included in the medical insurance, and is only reimbursed for patients who meet the indications. The price of the 130mg/26ml intravenous injection preparation may be more than 5,000 yuan per box, and the price of the 90mg: 1.0ml*1 subcutaneous injection preparation may be more than 8,000 yuan per box. The price of the 130mg/26ml intravenous injection preparation of Ustekinumab sold overseas may be more than 2,000 US dollars per box, and the price of 45mg: 0.5ml*1 subcutaneous injection preparation per box may be more than 10,000 US dollars. There are currently no generic versions of ustekinumab produced in other overseas countries.