Risankizumab

Risankizumab is a humanised monoclonal IgG1 antibody that binds the p19 subunit of interleukin 23, used in plaque psoriasis, psoriatic arthritis, Crohn disease and ulcerative colitis. It has the longest usual maintenance interval of the interleukin 23 inhibitors.

Class. Interleukin 23 p19 inhibitor monoclonal antibody.

Mechanism. Binds p19 selectively and blocks interleukin 23 signalling, limiting T helper 17 and innate lymphoid cell responses.

Pharmacokinetics. Subcutaneous bioavailability about 89 percent, half-life about 28 days, steady state by about week 16.

Plaque psoriasis and psoriatic arthritis.

• 150 mg subcutaneously at weeks 0 and 4, then every 12 weeks.

• Maximum dose: 150 mg for each dose.

Crohn disease.

• Induction: 600 mg intravenously over at least 1 hour at weeks 0, 4 and 8.

• Maintenance: 180 mg or 360 mg subcutaneously by on-body injector at week 12, then every 8 weeks.

Ulcerative colitis.

• Induction: 1200 mg intravenously over at least 2 hours at weeks 0, 4 and 8.

• Maintenance: 180 mg or 360 mg subcutaneously at week 12, then every 8 weeks.

Maintenance dose choice. The higher maintenance dose is used for high disease burden or inadequate response to the lower dose.

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 hepatotoxicity in Crohn disease induction, hypersensitivity and infection.

Adverse effects. Common: upper respiratory infection, headache, fatigue, injection site reactions, tinea infections, arthralgia. Serious: hepatotoxicity (raised transaminases and drug-induced liver injury during Crohn disease induction), anaphylaxis, serious infection.

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

Common prescribing errors. Missing baseline and induction liver tests in Crohn disease; using the psoriasis schedule in bowel disease; not completing tuberculosis screening.

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 advised in active hepatic disease or cirrhosis in Crohn disease; monitor enzymes.

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

Formulations. 150 mg prefilled pen or syringe, 600 mg and 1200 mg intravenous induction (diluted vials), and 180 mg and 360 mg on-body injector cartridges. Store at 2 to 8 degrees Celsius and protect from light.

Baseline. Tuberculosis screen, hepatitis B and C and HIV serology, ALT, AST, alkaline phosphatase and bilirubin, full blood count, and vaccination update.

Monitoring. Liver tests at baseline and during induction in Crohn disease (at least up to 12 weeks), then clinically indicated. Response at 16 weeks in psoriasis, then every 6 to 12 months.

Stop or hold thresholds. Suspected drug-induced liver injury (interrupt until excluded), serious infection, anaphylaxis, or no response by 24 weeks in psoriasis.

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