Biologic DMARDs

Biologic disease-modifying antirheumatic drugs (bDMARDs) are engineered proteins that block specific cytokines, cells or co-stimulatory signals in immune-mediated inflammatory disease.

Classes target tumour necrosis factor, interleukin 6, interleukin 17, interleukin 12 and 23, B cells and T cell costimulation. They are used when csDMARDs fail after about 3 to 6 months, and they improve control and slow structural damage, with higher infection risk and cost.

Mechanism. Monoclonal antibodies or receptor fusion proteins bind soluble or cell-surface targets and interrupt cytokine signalling or cell activity. Biosimilars share the same amino acid sequence and give similar clinical results at lower cost.

Pharmacokinetics. Injected or infused (subcutaneous or intravenous); long half-lives (days to weeks); no hepatic metabolism; antidrug antibodies lower response, reduced by co-prescribed methotrexate.

Before starting. Screen for tuberculosis (symptoms, chest X-ray, interferon-gamma release assay or tuberculin test), hepatitis B (HBsAg, anti-HBc), hepatitis C and HIV; update vaccinations (pneumococcal, influenza, hepatitis B, zoster inactivated) ahead of therapy; exclude active infection and pregnancy.

Choice. Select by disease: TNF inhibitors are usually first, rituximab for patients with lymphoma history or latent tuberculosis risk, tocilizumab when methotrexate cannot be used, interleukin 17 or 23 inhibitors for psoriasis and axial disease.

• First-line. After failing at least two csDMARDs (rheumatoid arthritis) or NSAIDs and physiotherapy (axial spondyloarthritis): a TNF inhibitor (or biosimilar).
• Alternative. Switch within class (second TNF inhibitor) or to another mechanism when the first fails or causes adverse effects.
• Specialist. Giant cell arteritis (tocilizumab), vasculitis and lupus (rituximab, belimumab), Behcet disease, uveitis, inflammatory bowel disease, severe psoriasis.
• Emergency. None; stop treatment during serious infection.

Treatment targets. Review at 12 weeks; stop or switch if the response falls short of target. Taper only after sustained remission, as flares are common.

Contraindications. Active serious infection (including untreated tuberculosis); hypersensitivity; heart failure NYHA class III or IV (TNF inhibitors); demyelinating disease (TNF inhibitors); hepatitis B without prophylaxis; live vaccines; pregnancy (case by case).

Serious adverse effects.

• Serious and opportunistic infection, reactivation of tuberculosis and hepatitis B.
• Infusion and injection-site reactions; antidrug antibodies.
• Demyelination, lupus-like syndrome, worsened heart failure (TNF inhibitors).
• Neutropenia and raised lipids (tocilizumab); diverticular perforation.
• Skin cancer and lymphoma (possible, uncertain).

Major interactions. Combining biologics (avoid); live vaccines; immunosuppressants add infection risk; methotrexate lowers immunogenicity and improves response.

Common prescribing errors.

• Starting without tuberculosis or hepatitis B screening.
• Continuing during sepsis.
• Giving live vaccines.
• Not checking response at 3 months.
• Switching when a dose reduction would have sufficed.

Special groups.

• Pregnancy: certolizumab has minimal placental transfer; other TNF inhibitors are used until 20 to 30 weeks; discuss with specialist.
• Breastfeeding: most are acceptable.
• Children: licensed agents for juvenile arthritis; specialist.
• Older adults: greater infection risk; careful screening.
• Kidney and liver: little adjustment; hepatitis B prophylaxis.
• East Africa: tuberculosis and hepatitis B are common, so screening and preventive therapy are essential (isoniazid or rifapentine-isoniazid for latent infection; tenofovir or entecavir for hepatitis B); cost and cold chain limit use; biosimilars widen access.

Monitoring. Infection symptoms at each visit; disease activity every 1 to 3 months; blood count and liver tests for each agent (tocilizumab every 4 to 8 weeks); tuberculosis symptoms yearly; skin examination.

Referral and escalation. Active infection or fever; neurological symptoms; heart failure; failure of two biologics; suspected malignancy.

Comparison with alternative classes. Biologics act faster and arrest joint damage better than csDMARDs alone in refractory disease, but need screening, monitoring and funding. Targeted synthetic agents (JAK inhibitors) are oral alternatives with different risks.