Interleukin 17 Pathway Inhibitors

Interleukin 17 (IL-17) inhibitors block a cytokine central to psoriasis, psoriatic arthritis and axial spondyloarthritis. Secukinumab, ixekizumab, bimekizumab and brodalumab give rapid, high rates of skin clearance and are alternatives to TNF inhibitors in axial disease. They are less useful in rheumatoid arthritis and worsen inflammatory bowel disease.

Mechanism. Secukinumab and ixekizumab bind IL-17A; bimekizumab binds IL-17A and IL-17F; brodalumab blocks the IL-17 receptor A. Reduced IL-17 signalling cuts keratinocyte activation, neutrophil recruitment and local inflammation.

Pharmacokinetics. Monoclonal antibodies with half-lives of about 4 weeks (secukinumab 27 days). Subcutaneous bioavailability about 55 to 77%.

Dose choice. Higher-dose secukinumab (300 mg) for heavier patients and for psoriasis; 150 mg for arthritis and axial disease without psoriasis, increased if response is inadequate.

Children. Secukinumab and ixekizumab are licensed for paediatric plaque psoriasis and enthesitis-related arthritis in some regions; weight-based.

• First-line. Moderate to severe plaque psoriasis after phototherapy or systemic therapy; axial spondyloarthritis after NSAID failure; psoriatic arthritis with skin involvement.
• Alternative. Switch after TNF inhibitor failure or intolerance, or when TNF inhibition is contraindicated (for example, heart failure or demyelination).
• Specialist. Hidradenitis suppurativa, enthesitis-related arthritis, palmoplantar pustulosis.
• Emergency. None.

Selection. Choose when skin clearance and rapid onset matter. Avoid in active or personal history of inflammatory bowel disease; use a TNF inhibitor (monoclonal antibody) or IL-23 inhibitor instead.

Contraindications. Active serious infection including untreated tuberculosis; hypersensitivity; active Crohn disease or ulcerative colitis (relative to absolute); brodalumab with depression or suicidal behaviour.

Serious adverse effects.

• Mucocutaneous Candida infection (oral, oesophageal, vulvovaginal).
• New onset or flare of inflammatory bowel disease.
• Upper respiratory infection, neutropenia, injection-site reactions.
• Rare hypersensitivity; tuberculosis reactivation (low risk).

Major interactions. Live vaccines; other biologics and immunosuppressants add infection risk; CYP substrates have minor effects.

Common prescribing errors.

• Using in patients with inflammatory bowel disease.
• Not asking about bowel symptoms before and after starting.
• Missing tuberculosis screening.
• Treating candidiasis without considering drug cause.
• Underdosing heavy patients with psoriasis.

Special groups.

• Pregnancy: limited data; avoid unless essential.
• Breastfeeding: unknown; avoid or specialist advice.
• Children: licensed for some indications; weight-based.
• Older adults: no adjustment; infection vigilance.
• Kidney and liver: no routine adjustment.
• East Africa: HIV-associated psoriasis is common and severe, and HIV and tuberculosis status must be known before use; cost and cold chain limit access; skin of colour may mask erythema, so assess with plaque thickness and itch.

Monitoring. Infection and candidiasis at each visit; bowel symptoms; skin and joint scores at 12 and 16 weeks; tuberculosis symptoms yearly; mood with brodalumab.

Referral and escalation. Bloody diarrhoea or new abdominal pain; severe candidiasis; failure by 16 weeks; suicidal thoughts (brodalumab); pregnancy.

Comparison with alternative classes. IL-17 inhibitors clear skin faster and more fully than TNF inhibitors and equal them in axial disease, but do not treat bowel disease or uveitis. IL-23 inhibitors have less candidiasis and rarer dosing.