What are the contraindications for different Tumor Necrosis Factor (TNF) inhibitors, such as etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade), used to treat Ankylosing Spondylitis (Ank Spon) in adults?

Contraindications for TNF Inhibitors in Ankylosing Spondylitis

The major contraindications to TNF inhibitors in ankylosing spondylitis are congestive heart failure, demyelinating disease, active tuberculosis, chronic infections, and high risk of recurrent infections, with specific alternative treatments recommended based on which contraindication is present. 1

Class-Wide Contraindications for All TNF Inhibitors

Cardiac Contraindications

• Congestive heart failure is a contraindication to all TNF inhibitors 1
• When CHF is the contraindication, switch to secukinumab or ixekizumab, as these IL-17 inhibitors have not been shown to worsen cardiac conditions 1

Neurologic Contraindications

• Demyelinating disease (including multiple sclerosis, optic neuritis, transverse myelitis) is a contraindication to all TNF inhibitors 1
• When demyelinating disease is the contraindication, prefer secukinumab or ixekizumab over TNF inhibitors 1
• Demyelinating neurologic disorders are a class effect of all anti-TNF drugs 2

Infectious Disease Contraindications

• Active tuberculosis is an absolute contraindication to all TNF inhibitors 1
• Chronic infections or high risk of recurrent infections contraindicate TNF inhibitor use 1
• When tuberculosis, chronic infection, or high infection risk is the contraindication, sulfasalazine is preferred over secukinumab, ixekizumab, and tofacitinib 1
• Efforts to mitigate infectious contraindications should be undertaken so that TNF inhibitors might be safely used once infection is controlled 1
• Reactivation of tuberculosis is a class effect of all anti-TNF drugs, though etanercept is less likely to induce TB reactivation than other TNF inhibitors 2
• Hepatitis B virus reactivation is a class effect of all anti-TNF drugs 2, 3

Hematologic Contraindications

• Hematologic disorders including aplastic anemia and pancytopenia are class effects of all anti-TNF drugs 2

Malignancy Considerations

• Lymphoma and other malignancies, some fatal, have been reported in patients treated with TNF blockers including adalimumab 4
• Hepatosplenic T-cell lymphoma (HSTCL), a rare and fatal T-cell lymphoma, has been reported with TNF blockers, particularly when combined with azathioprine or 6-mercaptopurine 4
• The majority of TNF blocker-associated HSTCL cases occurred in patients with Crohn's disease or ulcerative colitis, predominantly in adolescent and young adult males 4

Other Class-Wide Contraindications

• Vasculitis is a class effect of all anti-TNF drugs 2
• Immunogenicity concerns exist for all TNF inhibitors, though etanercept may be less immunogenic, especially in ankylosing spondylitis 2

Drug-Specific Considerations

Etanercept-Specific Limitations

• Etanercept is NOT efficacious in inflammatory bowel disease 1, 2
• When concomitant inflammatory bowel disease (especially Crohn's disease) is present, prefer TNF monoclonal antibodies (infliximab, adalimumab, certolizumab, golimumab) over etanercept 5
• Etanercept's efficacy in treating uveitis appears lower than other anti-TNF drugs 2
• Acute uveitis, Crohn's disease, and sarcoidosis are adverse events rarely associated with etanercept therapy 2

TNF Monoclonal Antibodies in IBD

• In patients with coexisting ulcerative colitis where TNF inhibitors are contraindicated, tofacitinib should be considered over secukinumab or ixekizumab 1
• IL-17 inhibitors (secukinumab, ixekizumab) have not been shown to be efficacious in inflammatory bowel disease 1

Common Adverse Events Requiring Monitoring

Injection Site Reactions

• The most common adverse effect of etanercept is injection-site reactions, which are generally self-limiting 2
• TNF-α inhibitors carry an increased incidence of adverse events and injection-site reactions compared to placebo 6

Infection Risk

• Bacterial, viral, and opportunistic infections including Legionella and Listeria can occur with adalimumab 4
• Carefully consider risks and benefits in patients with chronic or recurrent infection 4
• Monitor patients closely for signs and symptoms of infection during and after treatment 4

Critical Clinical Algorithm

When TNF inhibitors are contraindicated, follow this decision pathway:

1. If contraindication is CHF or demyelinating disease: Use secukinumab or ixekizumab 1

2. If contraindication is tuberculosis, chronic infection, or high infection risk: Use sulfasalazine (only for peripheral arthritis, not axial disease) and work to mitigate infection risk to allow future TNF inhibitor use 1

3. If contraindication is inflammatory bowel disease AND patient needs biologic: Use TNF monoclonal antibodies (infliximab, adalimumab, certolizumab, golimumab), NOT etanercept 5, 2

4. If contraindication is IBD AND TNF inhibitors cannot be used: Consider tofacitinib over IL-17 inhibitors 1

Common Pitfalls to Avoid

• Do not use rituximab, abatacept, ustekinumab, or interleukin-6 inhibitors even in patients with contraindications to TNF inhibitors, as these lack effectiveness in ankylosing spondylitis 1
• Do not use etanercept in patients with inflammatory bowel disease, as it is ineffective for IBD 1, 2
• Do not use IL-17 inhibitors (secukinumab, ixekizumab) in patients with inflammatory bowel disease, as they are not efficacious for IBD 1
• Do not ignore latent tuberculosis screening before initiating TNF inhibitors, as TB reactivation can occur even in patients who tested negative initially 4
• Do not combine TNF inhibitors with azathioprine or 6-mercaptopurine in adolescent or young adult males due to increased risk of hepatosplenic T-cell lymphoma 4