Tumour necrosis factor-α inhibitors

Background

• TNF-α is a cytokine involved in the inflammatory response to infection
• Has soluble and transmembrane forms
• Produced by macrophages, NK cells, granulocytes, fibroblasts, and T cells
• Receptors for TNF-α (TNFR1 and TNFR2) are found on most human cells, and are involved in cell activation and proliferation, cytokine production, and granuloma formation

Medications

• Adalimumab
• Infliximab
• Certolizumab pegol
• Etanercept

Contraindications

• Active bacterial infection, active tuberculosis or untreated LTBI, active herpes zoster infection, active invasive fungal infection, infected skin ulcers, acute hepatitis B or C, untreated chronic hepatitis B, or chronic hepatitis B or C with Child-Pugh B or C

Safety

• Baseline TST, ±CXR, prior to starting medications, with patients identified as having LTBI being offered prophylaxis
  • Cutoff for TST is 5 mm
• Assess for hepatitis B prophylaxis

Adverse Effects

Infections

• Bacteria: septic arthritis, Listeria monocytogenes, Legionella, Nocardia, Actinomyces, Salmonella
• Mycobacteria: Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium bovis, BCG
  • Risk of TB is higher for infliximab and adalimumab compared to etanercept
• Fungi: Aspergillus fumigatus, Histoplasma capsulatum, Coccidioides, Cryptococcus neoformans, Candida albicans
• Parasites: Toxoplasma gondii
• Viruses: hepatitis B virus, hepatitis C virus, varicella-zoster virus
• Screening prior to use should be done for LTBI (TST or IGRA), hepatitis B, hepatitis C, and HIV