Ustekinumab

Ustekinumab is a human monoclonal IgG1 antibody that binds the shared p40 subunit of interleukin 12 and interleukin 23. It is used in plaque psoriasis, psoriatic arthritis, Crohn disease and ulcerative colitis, with an intravenous weight-based induction in bowel disease and a long maintenance interval. Biosimilar versions are used and are not distinguished here.

Class. Interleukin 12 and interleukin 23 inhibitor monoclonal antibody.

Mechanism. Binding the p40 subunit prevents interaction with the interleukin 12 receptor beta 1 chain, blocking T helper 1 and T helper 17 differentiation and cytokine release.

Pharmacokinetics. Subcutaneous bioavailability about 57 percent, half-life about 3 weeks. Clearance rises with body weight, which is why a higher dose is used over 100 kg in psoriasis.

Plaque psoriasis (adult).

• 45 mg subcutaneously at weeks 0 and 4, then every 12 weeks for patients of 100 kg or less.

• 90 mg at weeks 0 and 4, then every 12 weeks for patients over 100 kg.

• Maximum dose: 90 mg for each dose.

Psoriatic arthritis. 45 mg at weeks 0 and 4, then every 12 weeks; 90 mg for patients over 100 kg or with coexisting moderate to severe psoriasis.

Crohn disease and ulcerative colitis.

• Loading dose: single intravenous infusion over at least 1 hour, by weight: 260 mg for 55 kg or less, 390 mg for over 55 kg to 85 kg, 520 mg for over 85 kg.

• Maintenance: 90 mg subcutaneously 8 weeks after the infusion, then 90 mg every 8 weeks, or every 12 weeks if disease is controlled; shorten to every 4 to 6 weeks for loss of response.

Paediatric plaque psoriasis (6 to under 18 years). Under 60 kg: 0.75 mg/kg at weeks 0 and 4, then every 12 weeks. 60 to 100 kg: 45 mg. Over 100 kg: 90 mg.

Response review. Reassess at 12 to 16 weeks in psoriasis; stop if there is no response by 28 weeks.

Contraindications. Clinically important active infection including tuberculosis, and serious hypersensitivity.

Boxed-warning-level risks. No boxed warning. Main hazards are serious infection, hypersensitivity including anaphylaxis, and rare posterior reversible encephalopathy syndrome.

Adverse effects. Common: nasopharyngitis, upper respiratory infection, headache, injection site reactions, arthralgia. Serious: serious infection including salmonellosis and mycobacterial disease in people with interleukin 12 and 23 signalling defects, hypersensitivity, interstitial pneumonia and eosinophilic pneumonia, exfoliative dermatitis, skin cancer.

Major interactions. Live vaccines (avoid), immunosuppressants and phototherapy in psoriasis (add risk), warfarin and ciclosporin (monitor levels as inflammation resolves).

Common prescribing errors. Using the 45 mg dose over 100 kg in psoriasis; not giving the intravenous induction in bowel disease; skipping tuberculosis screening.

Special groups.

• Pregnancy: crosses the placenta mainly in the third trimester; use only if benefit outweighs risk, and delay live vaccines in the infant for 6 to 12 months if exposed late.

• Breastfeeding: likely compatible.

• Children: from 6 years in psoriasis, 0.75 mg/kg under 60 kg, 45 mg for 60 to 100 kg and 90 mg over 100 kg at weeks 0 and 4 then every 12 weeks.

• Older adults: no adjustment; closer infection monitoring.

• Kidney impairment: no adjustment expected.

• Liver impairment: no adjustment expected.

• Region: tuberculosis and hepatitis B screening and refrigerated storage are needed; ask about recurrent salmonella or mycobacterial infection before starting.

Formulations. 45 mg and 90 mg prefilled syringes; 130 mg intravenous vial diluted to 250 mL in 0.9 percent sodium chloride and infused over at least 1 hour through a low protein binding filter. Store at 2 to 8 degrees Celsius.

Baseline. Tuberculosis screen, hepatitis B and C and HIV serology, full blood count, liver enzymes, vaccination update, and skin cancer screen in psoriasis.

Monitoring. Response at 12 to 16 weeks, then every 6 to 12 months. In bowel disease, symptom score and faecal calprotectin.

Stop or hold thresholds. Serious infection, anaphylaxis, new unexplained respiratory symptoms, or no response by 28 weeks.

Referral and escalation. Specialist initiated. Refer for recurrent infection or loss of response.