Ixekizumab

Ixekizumab is a humanised monoclonal IgG4 antibody that neutralises interleukin 17A, given subcutaneously, used in plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis. It acts quickly on skin disease and has little effect on gut inflammation, but can worsen inflammatory bowel disease.

Class. Interleukin 17A inhibitor monoclonal antibody.

Mechanism. Binds interleukin 17A (homodimer and heterodimer with 17F), blocking keratinocyte activation, neutrophil recruitment and synovial inflammation.

Pharmacokinetics. Subcutaneous bioavailability about 60 to 81 percent, peak at 4 to 7 days, half-life about 13 days, steady state by about week 8 in psoriasis.

Plaque psoriasis (adult).

• Loading dose: 160 mg subcutaneously (two 80 mg injections) at week 0.

• Induction: 80 mg at weeks 2, 4, 6, 8, 10 and 12.

• Maintenance dose: 80 mg every 4 weeks.

• Maximum dose: 160 mg for the first dose, 80 mg for each later dose.

Psoriatic arthritis (without moderate to severe psoriasis). 160 mg at week 0, then 80 mg every 4 weeks. With coexisting moderate to severe psoriasis, use the psoriasis regimen.

Ankylosing spondylitis and non-radiographic axial spondyloarthritis. 160 mg at week 0, then 80 mg every 4 weeks.

Paediatric plaque psoriasis (6 to under 18 years). Over 50 kg: 160 mg at week 0 then 80 mg every 4 weeks. 25 to 50 kg: 80 mg at week 0 then 40 mg every 4 weeks. Under 25 kg: 40 mg at week 0 then 20 mg every 4 weeks.

Response review. Reassess at 12 to 16 weeks; consider stopping if there is no response by 16 to 20 weeks.

Contraindications. Serious hypersensitivity, and clinically important active infection such as active tuberculosis. Avoid in active inflammatory bowel disease.

Boxed-warning-level risks. No boxed warning. Main hazards are new or worsening inflammatory bowel disease, serious hypersensitivity including angioedema, and mucocutaneous candidiasis.

Adverse effects. Common: injection site reactions, upper respiratory infection, nausea, tinea infections. Serious: Crohn disease or ulcerative colitis onset or flare, neutropenia, anaphylaxis, angioedema, serious infection, eczematous eruptions.

Major interactions. Live vaccines (avoid). No important metabolic interactions are established. Avoid combining with other biologics.

Common prescribing errors. Prescribing in a patient with active inflammatory bowel disease; omitting the 160 mg first dose; skipping tuberculosis screening.

Special groups.

• Pregnancy: limited data; avoid if possible.

• Breastfeeding: limited data; likely low milk transfer.

• Children: weight-based as stated for psoriasis from 6 years.

• Older adults: no adjustment.

• Kidney impairment: not studied; no adjustment expected.

• Liver impairment: not studied; no adjustment expected.

• Region: tuberculosis screening is advised before starting, and refrigerated storage is needed.

Formulations. 80 mg prefilled pens and syringes, 40 mg and 20 mg paediatric syringes. Inject into the thigh, abdomen or upper arm. Store at 2 to 8 degrees Celsius; may be kept at room temperature for up to 5 days.

Baseline. Tuberculosis screen, hepatitis B and C and HIV serology, full blood count, bowel symptom history, and vaccination update.

Monitoring. Response at 12 to 16 weeks, then every 6 to 12 months. Ask about diarrhoea, abdominal pain, candidiasis and infection at each visit.

Stop or hold thresholds. New or worsening inflammatory bowel disease, serious infection, serious hypersensitivity, or no response by 16 to 20 weeks.

Referral and escalation. Specialist initiated. Refer to gastroenterology for persistent diarrhoea or rectal bleeding.