What are the contraindications for using Tumor Necrosis Factor-alpha (TNFa) inhibitors, such as etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade), and Interleukin-23 (IL23) inhibitors, such as ustekinumab (Stelara), guselkumab (Tremfya), or risankizumab (Skyrizi), in patients with psoriasis?

Contraindications for TNF-α Inhibitors and IL-23 Inhibitors in Psoriasis

Absolute Contraindications

TNF-α Inhibitors (Adalimumab, Infliximab, Etanercept)

TNF-α inhibitors are absolutely contraindicated in patients with severe congestive heart failure (NYHA class III or IV), active serious infections, and demyelinating disease. 1

• Severe heart failure (NYHA class III or IV): TNF-α inhibitors should be avoided entirely in this population, as they can worsen pre-existing heart failure or precipitate new-onset heart failure 1, 2
• Active serious infections: Treatment must not be initiated during active serious infections, including sepsis, abscess, or opportunistic infections 1
• Active tuberculosis: Absolute contraindication until TB is adequately treated; all patients require TB screening before initiation 1
• Demyelinating disease: TNF-α inhibitors are contraindicated in patients with multiple sclerosis or other demyelinating conditions, as they can worsen disease severity 1, 3

IL-23 Inhibitors (Guselkumab, Risankizumab, Tildrakizumab)

IL-23 inhibitors have only one absolute contraindication: history of serious hypersensitivity reaction to the drug or its excipients. 4

• Serious hypersensitivity: Risankizumab is contraindicated in patients with prior serious hypersensitivity to risankizumab-rzaa or any excipients 4
• Note: IL-23 inhibitors have a more favorable contraindication profile compared to TNF-α inhibitors, with no absolute contraindications for heart failure, demyelinating disease, or tuberculosis 1, 5

Relative Contraindications and Special Precautions

TNF-α Inhibitors

Use extreme caution and consider alternative agents in the following scenarios:

• Mild-moderate heart failure (NYHA class I-II): Requires careful assessment and close monitoring; withdraw treatment if symptoms worsen 1
• History of malignancy: While TNF-α inhibitors as monotherapy do not increase solid tumor or lymphoma risk, patients with recent malignancy (particularly within 5 years) require careful risk-benefit assessment 1
• Hepatitis B infection: Not an absolute contraindication, but requires hepatology consultation, antiviral prophylaxis, and monitoring of HB surface antigen, anti-HB core antibody, and liver function tests 1
• HIV infection: Can be used only if patient is on highly active antiretroviral therapy (HAART) with normalized CD4+ counts, undetectable viral load, and no recent opportunistic infections; requires infectious disease consultation 1
• Hepatitis C infection: Use with caution; monitor liver function closely 1
• History of lupus or lupus-like syndromes: TNF-α inhibitors can induce or worsen lupus-like reactions 2, 3

IL-23 Inhibitors

Use caution in patients with pre-existing immunosuppression-related conditions, though these are not absolute contraindications. 1, 5

• Active infections: While not absolutely contraindicated, screen for and treat active infections before initiating therapy 5
• Tuberculosis: Screen all patients for latent TB before treatment; the mechanism of action suggests potential for TB reactivation, though no cases were reported in initial trials 1
• Pregnancy: Limited data exist, but safety profile expected to be similar to ustekinumab with no significant increase in adverse pregnancy outcomes 5
• Respiratory comorbidities: Monitor vigilantly for respiratory symptoms and infections 5

Critical Screening Requirements Before Initiation

For TNF-α Inhibitors

Mandatory screening includes tuberculosis testing, hepatitis B and C serology, and assessment for active infections. 1

• Tuberculosis screening: Tuberculin skin test or interferon-gamma release assay (IGRA); chest X-ray if positive 1
• Hepatitis B: HB surface antigen, anti-HB core antibody, and anti-HB surface antibody 1
• Hepatitis C: Anti-HCV antibody 1
• Complete blood count: Assess for baseline cytopenias 2
• Cardiac assessment: Evaluate for heart failure symptoms and consider echocardiography if history suggests cardiac disease 1

For IL-23 Inhibitors

Screen for active infections, tuberculosis, and malignancy at baseline; ensure vaccinations are current. 5

• Tuberculosis screening: Same as TNF-α inhibitors 5
• Vaccination status: Complete pneumococcal and influenza vaccinations before initiating therapy 5
• Malignancy screening: Age-appropriate cancer screening 5
• Infection assessment: Rule out active infections 5

Common Pitfalls and Clinical Pearls

The most critical error is failing to screen for latent tuberculosis before initiating TNF-α inhibitors, as reactivation risk is approximately six times higher than in untreated patients. 1

• TNF-α inhibitors carry significantly more contraindications than IL-23 inhibitors, making IL-23 inhibitors preferable for patients with cardiac disease, demyelinating conditions, or complex medical histories 1, 5
• Brodalumab (IL-17 inhibitor, not IL-23) has a unique contraindication: suicidal ideation or recent suicidal behavior, requiring enrollment in a REMS program 1
• Weight-based dosing matters: Infliximab uses weight-based dosing (5 mg/kg), which may be advantageous in obese patients compared to fixed-dose TNF-α inhibitors 1
• Combination immunosuppression increases risk: Adding other immunosuppressants to TNF-α inhibitors may alter the safety profile and increase malignancy risk 1
• Prior PUVA therapy: Patients with extensive PUVA exposure may be at higher risk for malignancy when treated with biologics 1