Secukinumab

Secukinumab is a fully human monoclonal IgG1 antibody that neutralises interleukin 17A, given subcutaneously, used in plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, hidradenitis suppurativa and juvenile enthesitis-related and psoriatic arthritis. It is a first-line biological for axial disease and a strong option for skin and enthesitis, but worsens Crohn disease.

Class. Interleukin 17A inhibitor monoclonal antibody.

Mechanism. Binds interleukin 17A, blocking keratinocyte and synovial cell inflammatory responses and neutrophil recruitment.

Pharmacokinetics. Subcutaneous bioavailability about 73 percent, half-life about 27 days, steady state after about 24 weeks without loading. Clearance is higher with body weight over 90 kg.

Plaque psoriasis.

• Loading dose: 300 mg subcutaneously (two 150 mg injections) at weeks 0, 1, 2, 3 and 4.

• Maintenance dose: 300 mg every 4 weeks. 150 mg every 4 weeks may be enough for patients under 90 kg.

• Maximum dose: 300 mg for each dose.

Psoriatic arthritis. 150 mg at weeks 0, 1, 2, 3 and 4, then 150 mg every 4 weeks; loading may be omitted. Use 300 mg for coexisting moderate to severe plaque psoriasis or inadequate response.

Ankylosing spondylitis and non-radiographic axial spondyloarthritis. 150 mg at weeks 0, 1, 2, 3 and 4, then every 4 weeks; loading may be omitted. May increase to 300 mg every 4 weeks.

Hidradenitis suppurativa. 300 mg at weeks 0, 1, 2, 3 and 4, then every 4 weeks; every 2 weeks for inadequate response.

Juvenile psoriatic and enthesitis-related arthritis (2 years and over). 75 mg for under 50 kg and 150 mg for 50 kg and over, at weeks 0, 1, 2, 3 and 4, then every 4 weeks.

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

Contraindications. Serious hypersensitivity, and clinically important active infection such as active tuberculosis. Avoid in active Crohn disease or ulcerative colitis.

Boxed-warning-level risks. There is no boxed warning, but mucocutaneous candidiasis, new or worsening inflammatory bowel disease, and serious hypersensitivity are the main hazards.

Adverse effects. Common: upper respiratory infection, nasopharyngitis, diarrhoea, headache, oral and genital candidiasis. Serious: new onset or flare of Crohn disease or ulcerative colitis, neutropenia, anaphylaxis, serious infection, eczematous eruptions.

Major interactions. Live vaccines (avoid) and other biologics. No clinically important metabolic interactions are established.

Common prescribing errors. Using in a patient with inflammatory bowel disease or uveitis as primary indication; omitting loading doses where needed for speed; no tuberculosis screening.

Special groups.

• Pregnancy: limited data; avoid if possible and use only if benefit outweighs risk.

• Breastfeeding: limited data; likely low milk transfer.

• Children: 75 mg (under 50 kg) or 150 mg (50 kg and over) every 4 weeks after loading.

• Older adults: no adjustment.

• Kidney impairment: not studied; no adjustment expected.

• Liver impairment: not studied; no adjustment expected.

• Region: tuberculosis screening is still advised before starting; the cold chain is needed for storage.

Formulations. 75 mg and 150 mg prefilled syringes and 150 mg or 300 mg pens, injected into the thigh, abdomen or upper arm. Store at 2 to 8 degrees Celsius; may be kept at room temperature up to 4 days.

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

Monitoring. Response at 12 to 16 weeks, then 6 to 12 monthly. Ask about diarrhoea, abdominal pain, candidiasis and infection at each visit. Full blood count when clinically indicated.

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

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