From the Guidelines
TNF antagonist therapy is associated with significant risks, including a increased risk of opportunistic infections and reactivation of latent tuberculosis.
Risks of TNF Antagonist Therapy
- Opportunistic Infections: The use of TNF antagonists has been linked to a small increased risk of opportunistic infections, particularly when used in combination with corticosteroids or immunosuppressants 1. A meta-analysis of 22 RCTs reported opportunistic infections in 0.9% of patients receiving anti-TNF therapies compared with 0.3% of patients receiving placebo (RR, 2.05; 95% CI, 1.10–3.85) 1.
- Reactivation of Latent Tuberculosis: TNF antagonist therapy is associated with a 2.5-fold increased risk of tuberculosis infection 1. The risk of reactivation of latent TB is higher in patients treated with anti-TNF agents, especially when used in combination with methotrexate or azathioprine 1.
- Malignancy: While there is no robust evidence of increased risk of malignancy with TNF antagonists in patients with psoriasis 1, a meta-analysis of nine trials of patients with RA treated with infliximab or adalimumab demonstrated a pooled odds ratio for malignancy of 3.3 (95% CI 1.2–9.1) 1. However, this finding is not consistent across all studies, and the evidence is not strong enough to support a definitive conclusion.
Patient Management
- Screening for Latent Tuberculosis: Patients should be screened for latent tuberculosis before starting TNF antagonist therapy, and annual re-screening may be considered for patients with a higher TB risk 1.
- Viral Screening: Patients starting biologics or immunosuppressive drugs should undergo viral screening if not done initially, or if new risk factors have arisen since that time 1.
- Monitoring for Infections: Patients on TNF antagonist therapy should be monitored for signs of opportunistic infections, and a high index of suspicion is required throughout treatment 1.
From the Research
Risks of TNF Antagonist Therapy
The use of TNF antagonist therapy has been associated with several risks, including:
- Increased risk of serious infection, with patients with rheumatoid arthritis appearing to have an approximately 2-fold increased risk of serious infection compared to the general population and non-RA controls, irrespective of TNF-α antagonist use 2
- Reactivation of latent infections, such as tuberculosis, with the relative risk for TB increased up to 25 times, depending on the clinical setting and the TNF antagonist used 3
- Increased risk of malignancy, including lymphoproliferative cancers in children and adolescents 2
- Infusion and injection site reactions, autoantibody formation, and drug-induced lupus erythematosus 4
- Liver function abnormalities, hematological, and solid organ malignancies 4
- Increased risk of non-melanoma skin cancer (NMSC), with some studies suggesting a small increased risk of squamous cell cancer in RA patients treated with TNFi 5
- Increased risk of inflammatory central nervous system (CNS) diseases, including demyelinating diseases, with an overall 36% increased risk of any inflammatory CNS disease compared to conventional therapies 6
Specific Risks Associated with TNF Antagonist Therapy
Some specific risks associated with TNF antagonist therapy include:
- Tuberculosis: The risk of reactivating latent TB is increased with TNF antagonist therapy, and screening for latent TB is recommended before starting treatment 3
- Cancer: The risk of cancer, including lymphoma and NMSC, may be increased with TNF antagonist therapy, although the evidence is not consistent across all studies 2, 5
- Inflammatory CNS diseases: The risk of inflammatory CNS diseases, including demyelinating diseases, may be increased with TNF antagonist therapy, with an overall 36% increased risk compared to conventional therapies 6
Management of Risks Associated with TNF Antagonist Therapy
To manage the risks associated with TNF antagonist therapy, the following measures can be taken:
- Baseline screening and periodic monitoring for latent TB and other infections 3
- Monitoring for signs and symptoms of malignancy, including lymphoma and NMSC 2, 5
- Monitoring for signs and symptoms of inflammatory CNS diseases, including demyelinating diseases 6
- Use of preventive chemotherapy for latent TB 3
- Careful consideration of the benefits and risks of TNF antagonist therapy in individual patients, taking into account their underlying disease and medical history 2, 4, 5, 6