Guselkumab

Guselkumab is a human monoclonal IgG1 antibody that binds the p19 subunit of interleukin 23, used in plaque psoriasis, psoriatic arthritis, ulcerative colitis and Crohn disease. It has a long interval between maintenance doses and a low rate of serious infection.

Class. Interleukin 23 p19 inhibitor monoclonal antibody.

Mechanism. Binds the p19 subunit and prevents interleukin 23 from signalling through its receptor, reducing T helper 17 maintenance and downstream cytokines.

Pharmacokinetics. Subcutaneous bioavailability about 49 percent, half-life about 17 days, steady state by about week 20.

Plaque psoriasis.

• 100 mg subcutaneously at weeks 0 and 4, then every 8 weeks.

• Maximum dose: 100 mg for each subcutaneous dose.

Psoriatic arthritis. 100 mg at weeks 0 and 4, then every 8 weeks; every 4 weeks may be used in those with high disease activity.

Ulcerative colitis.

• Induction: 200 mg intravenously over at least 1 hour at weeks 0, 4 and 8, or 400 mg subcutaneously at weeks 0, 4 and 8.

• Maintenance: 100 mg subcutaneously every 8 weeks starting at week 16, or 200 mg every 4 weeks starting at week 12.

Crohn disease. Induction 200 mg intravenously at weeks 0, 4 and 8, or 400 mg subcutaneously at weeks 0, 4 and 8; maintenance 100 mg subcutaneously every 8 weeks from week 16, or 200 mg every 4 weeks from week 12.

Response review. Reassess at 16 weeks in psoriasis; consider stopping if no response by 24 weeks.

Contraindications. Serious hypersensitivity, and clinically important active infection such as active tuberculosis.

Boxed-warning-level risks. No boxed warning. Main hazards are hypersensitivity, raised transaminases during intravenous induction, and infection.

Adverse effects. Common: upper respiratory infection, headache, injection site reactions, arthralgia, gastroenteritis, raised transaminases. Serious: anaphylaxis, serious infection, hepatotoxicity during bowel disease induction.

Major interactions. Live vaccines (avoid). No important metabolic interactions are established.

Common prescribing errors. Using the psoriasis dose for bowel disease; skipping liver tests during induction; screening for tuberculosis late.

Special groups.

• Pregnancy: limited data; avoid if possible.

• Breastfeeding: limited data; likely low milk transfer.

• Children: not established for routine rheumatological use.

• Older adults: no adjustment.

• Kidney impairment: no adjustment expected.

• Liver impairment: not studied; monitor enzymes.

• Region: tuberculosis and hepatitis B screening before starting; refrigerated storage is needed.

Formulations. 100 mg prefilled pens and syringes, 200 mg and 400 mg subcutaneous induction presentations, and 200 mg intravenous vial diluted in 0.9 percent sodium chloride. Store at 2 to 8 degrees Celsius.

Baseline. Tuberculosis screen, hepatitis B and C and HIV serology, liver enzymes and bilirubin, full blood count, and vaccination update.

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

Stop or hold thresholds. Serious infection, anaphylaxis, ALT over 5 times the upper limit of normal, or no response by 24 weeks in psoriasis.

Referral and escalation. Specialist initiated. Refer for persistent liver enzyme elevation or loss of response.