Infections Related to Anti-TNF Drug Use
Anti-TNF drugs significantly increase the risk of serious infections, particularly tuberculosis, opportunistic fungal infections, and bacterial infections, with patients frequently presenting with disseminated rather than localized disease.
Types of Infections Associated with Anti-TNF Therapy
Tuberculosis
- Tuberculosis is the most common serious opportunistic infection associated with anti-TNF therapy 1
- Extrapulmonary and disseminated TB occurs in at least 50% of cases 1
- Risk of TB reactivation is 5-7 times higher in patients on anti-TNF therapy compared to the general population 2
- Monoclonal antibodies (infliximab, adalimumab) carry a higher TB risk than soluble receptor (etanercept) 1, 3
- Infliximab: 103 cases per 100,000 patient-years
- Adalimumab: 171 cases per 100,000 patient-years
- Etanercept: 39 cases per 100,000 patient-years 1
Fungal Infections
- Opportunistic fungal infections reported with anti-TNF therapy include 2, 4, 5:
- Histoplasmosis
- Coccidioidomycosis
- Cryptococcosis
- Aspergillosis
- Candidiasis
- Pneumocystis jirovecii pneumonia
Bacterial Infections
- Upper respiratory tract infections are the most common bacterial infections 2
- Serious bacterial infections include 4, 5:
- Legionellosis
- Listeriosis
- Salmonellosis
- Nocardia infections
Viral Infections
Risk Factors for Infections with Anti-TNF Therapy
- Age over 50 years increases risk of opportunistic infections (OR 3.0) 2, 1
- Combination therapy with other immunosuppressants significantly increases risk:
- Type of anti-TNF agent: Monoclonal antibodies (infliximab, adalimumab) carry higher infection risk than soluble receptor (etanercept) 1, 3
- Comorbidities: Diabetes, COPD, chronic kidney disease 2
- Prior history of infections or tuberculosis 4, 5
- Geographic factors: Residence or travel to areas endemic for TB or fungal infections 4, 5
Timing and Presentation of Infections
- Median time to TB onset varies by agent 1:
- Infliximab: 3 months
- Adalimumab: 4-6 months
- Etanercept: 11.5 months
- Infections often present atypically with extrapulmonary manifestations 1
- Patients frequently present with disseminated rather than localized disease 4, 5
Prevention Strategies
Pre-treatment Screening
- Tuberculosis screening is mandatory before starting anti-TNF therapy 2, 4, 5:
- Tuberculin skin test (TST) or interferon-gamma release assay (IGRA)
- Chest radiograph
- Detailed history of TB exposure and symptoms
- Hepatitis B and C serology should be obtained prior to therapy 2
- Assessment for fungal infection risk in endemic areas for histoplasmosis, blastomycosis, or coccidioidomycosis 4, 5
Prophylaxis and Management
- Treatment of latent TB infection prior to anti-TNF therapy reduces reactivation risk 4, 5
- Anti-TNF therapy should not be initiated in patients with active infection 4, 5
- In case of serious infection during treatment, anti-TNF therapy should be discontinued 4, 5
- Patients should be closely monitored for signs and symptoms of infection during treatment 4, 5
Clinical Pitfalls and Caveats
- False-negative TB tests may occur in immunosuppressed patients 4, 5
- TB reactivation can occur despite prophylaxis 7
- Patients may present with atypical or extrapulmonary manifestations of infection 1
- Infections may have blunted inflammatory responses due to TNF inhibition, making diagnosis challenging 1
- Elderly patients require extra vigilance due to higher infection risk 2
By understanding these infection risks and implementing appropriate screening and monitoring strategies, clinicians can optimize the safety profile of anti-TNF therapy while effectively managing inflammatory conditions.