What is the role of targeted biological agents in the treatment of AA (inflammatory) amyloidosis?

Updated: Aug 11, 2020
  • Author: Richa Dhawan, MD, CCD; Chief Editor: Herbert S Diamond, MD  more...
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Biologic agents targeting proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, and IL-6 have been tried in patients with AA amyloidosis. Treatment with tumor necrosis factor–α (TNF-α) inhibitors and interleukin-1 (IL-1) inhibitors has proved effective in controlling the progression of renal amyloid in patients with inflammatory arthritides and hereditary periodic fevers. The rationale for using TNF inhibitors in secondary amyloidosis comes from the fact that these medications lower levels of serum IL-6, which is an important mediator of the acute phase inflammatory response. Lowering of IL-6 levels results in reduced synthesis of acute-phase proteins, suppression of systemic inflammation, and lower SAA levels, leading to reduction of amyloid deposits. [35]

Anakinra, a recombinant form of IL-1 receptor antagonist, has shown favorable effects on dermatologic and rheumatic manifestations in patients with Muckle–Wells syndrome and familial cold autoinflammatory syndrome. This treatment also resulted in the resolution of AA amyloidosis in these patients. [36]

IL-6 is one of the pro-inflammatory cytokines playing a critical role in the induction of SAA genes, thus inhibition of IL-6 results in dramatic suppression of SAA. Tocilizumab (TCZ), a humanized monoclonal anti IL-6 receptor antibody, was effective in the treatment of amyloidosis secondary to various rheumatic diseases. It binds to soluble and membrane-bound IL-6 receptors and down regulates the synthesis of IL-6 with significant decrease in SAA levels. [37]  

A retrospective study that indirectly compared tocilizumab to anti-TNFs, with a median treatment duration of 2 years suggested a more favorable outcome with tocilizumab. Although IL-6 blockage seems to have the advantage of significantly reducing circulating SAA levels, its long-term impact on renal function is not known. Moreover, switching between these agents is frequently necessary in inflammatory conditions due to adverse events and primary or secondary inefficacy. [38]

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