TNF Inhibitors

Tumour necrosis factor (TNF) inhibitors are the most widely used biologic class. They treat rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, juvenile arthritis, Crohn disease, ulcerative colitis, psoriasis, uveitis and hidradenitis suppurativa. Several agents and biosimilars exist, and the choice depends on disease, route, interval and cost.

Mechanism. They bind soluble and membrane TNF, preventing receptor signalling and reducing inflammation, cell recruitment and bone erosion. Monoclonal antibodies (adalimumab, infliximab, golimumab, certolizumab) also cause cell lysis; etanercept is a soluble receptor fusion protein.

Pharmacokinetics. Half-lives: adalimumab about 2 weeks, etanercept 3 to 5 days, infliximab 8 to 10 days, certolizumab about 2 weeks, golimumab about 2 weeks. Antidrug antibodies reduce levels and efficacy.

Children. Adalimumab 20 mg (under 30 kg) or 40 mg every 2 weeks; etanercept 0.8 mg/kg weekly (maximum 50 mg).

Switching. If the first TNF inhibitor fails because of antibody formation, a second may work; primary failure suggests another mechanism.

Tapering. After sustained remission for 6 to 12 months, lengthen the interval or reduce the dose with monitoring; flares are common if stopped completely.

• First-line. Rheumatoid arthritis after csDMARD failure; axial spondyloarthritis after NSAIDs; psoriatic arthritis; Crohn disease and ulcerative colitis (infliximab, adalimumab); non-infectious uveitis (adalimumab).
• Alternative. Etanercept for arthritis in patients with demyelinating-disease concerns; certolizumab in pregnancy.
• Specialist. Juvenile arthritis, hidradenitis suppurativa, Behcet disease, refractory sarcoidosis.
• Emergency. None.

Selection. Use a monoclonal antibody for inflammatory bowel disease, uveitis and granulomatous disease; any agent for arthritis; add methotrexate with infliximab and adalimumab to reduce antibodies; use the cheapest biosimilar.

Contraindications. Active tuberculosis or serious infection; heart failure NYHA class III or IV; demyelinating disease; hypersensitivity; live vaccines; hepatitis B without antiviral cover; lupus or lupus-like syndrome.

Serious adverse effects.

• Infection (tuberculosis reactivation, hepatitis B reactivation, bacterial and fungal infection, herpes zoster).
• Infusion reactions with infliximab; injection-site reactions with subcutaneous agents.
• Demyelination and optic neuritis; lupus-like syndrome; paradoxical psoriasis.
• Worsened heart failure; blood dyscrasias; hepatotoxicity.
• Skin cancers; lymphoma in young patients with inflammatory bowel disease on combined immunosuppression.

Major interactions. Abatacept and anakinra (more infection; avoid); azathioprine and mercaptopurine with infliximab (hepatosplenic T cell lymphoma risk in young men); live vaccines; methotrexate reduces antibody formation.

Common prescribing errors.

• Screening tests missed or not repeated.
• Continuing through serious infection or surgery.
• Using etanercept for Crohn disease.
• Giving infliximab without methotrexate or azathioprine.
• Live vaccines to infants exposed in pregnancy.

Special groups.

• Pregnancy: certolizumab throughout; others usually stopped by 20 to 30 weeks; avoid live vaccines for the infant for 6 months after exposure.
• Breastfeeding: acceptable.
• Children: weight-based dosing; specialist.
• Older adults: higher infection risk.
• Kidney and liver: no routine adjustment.
• East Africa: high tuberculosis and hepatitis B burden make screening and preventive treatment mandatory; start TNF inhibitors only after latent tuberculosis therapy begins (at least 1 month earlier where possible); supply is variable, so plan continuity before starting.

Monitoring. Disease activity every 1 to 3 months; full blood count and liver tests every 3 to 6 months; tuberculosis symptoms and chest X-ray as indicated; skin checks; antidrug antibodies and drug levels where available.

Referral and escalation. Fever or suspected infection; new neurological symptoms; heart failure; failure to respond at 12 weeks; planned surgery; pregnancy.

Comparison with alternative classes. TNF inhibitors have the longest record, and biosimilars lower costs. They are less suitable than rituximab for patients with lymphoma history, than tocilizumab when methotrexate cannot be co-prescribed, and than interleukin 17 or 23 inhibitors in some psoriasis phenotypes.