What is the role of TNF-α inhibitors in the treatment of ankylosing spondylitis (AS) and undifferentiated spondyloarthropathy (USpA)?

Updated: Feb 02, 2021
  • Author: Lawrence H Brent, MD; Chief Editor: Herbert S Diamond, MD  more...
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TNF is a cytokine with two identified forms, which have similar biologic properties. TNF-α (cachectin) is produced predominantly by macrophages, and TNF-β (lymphotoxin) is produced by lymphocytes. TNF is but one of many cytokines involved in the inflammatory cascade that may contribute to AS. [114, 107]

TNFi have been shown to be very effective in the treatment of AS. [115] They have a fairly rapid onset of action (2 weeks), and have been shown to reduce the inflammatory activity of spinal disease as assessed with magnetic resonance imaging (MRI). [116]

The European League Against Rheumatism notes that extensive MRI inflammatory activity, particularly in the spine, might be used as a predictor of good clinical response to TNFi treatment in patients with AS. Thus, MRI might aid in the decision of initiating TNFi, in addition to clinical examination and C-reactive protein (CRP) testing. [91]

TNFi are indicated after NSAID therapy has failed (two different NSAIDs for one month each). [99] The following TNFi have been approved by the US Food and Drug Administration (FDA) as therapies for AS:

TNFi are also approved for the treatment of rheumatoid arthritis and psoriatic arthritis (PsA). Other approved indications include the following:

  • Psoriasis (etanercept, infliximab, adalimumab, certolizumab pegol)
  • Juvenile idiopathic arthritis (etanercept, adalimumab)
  • Crohn disease (infliximab, adalimumab, certolizumab pegol)
  • Non-infectious uveitis (adalimumab)

Toxicities associated with TNFi include injection-site and infusion reactions. Increased risks of bacterial infections, reactivation of latent tuberculosis, and certain fungal infections (eg, histoplasmosis, coccidioidomycosis) have been observed.

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