Effectiveness of etanercept vs cyclophosphamide as treatment for patients with amyloid A amyloidosis secondary to rheumatoid arthritis

Rheumatology (Oxford). 2012 Nov;51(11):2064-9. doi: 10.1093/rheumatology/kes190. Epub 2012 Aug 9.


Objectives: To compare the effectiveness of an alkylating agent with that of a biologic agent in the treatment of patients with amyloid A (AA) amyloidosis secondary to RA and to assess the association of the serum AA (SAA) 1.3 allele with treatment.

Methods: CYC and etanercept (ETN) were administered to 62 and 24 RA patients, respectively, who were confirmed with biopsy as having AA amyloidosis. We evaluated whether the SAA1.3 allele, a factor indicating genetic risk and poor prognosis of Japanese RA patients with AA amyloidosis, influenced treatments and retrospectively analysed the effectiveness of both agents via statistical methods.

Results: Two treatment groups were similar, except for the SAA1.3 genotype (P = 0.015) and duration of AA amyloidosis since diagnosis (P < 0.001). Also, patients given ETN had somewhat worse renal function, i.e. 24-h proteinuria (P = 0.02), at the initiation of treatment. ETN demonstrated greater effectiveness than CYC, as shown by significantly improved levels of serum CRP and serum albumin (both P < 0.01) and estimated glomerular filtration rate (eGFR; P = 0.032). ETN improved survival (P = 0.025), and the hazard ratios for the risk of death endpoint with eGFR and 24-h proteinuria were significant by P = 0.024 and P = 0.025, respectively. The SAA1.3 allele did not affect the response to medications in AA amyloidosis secondary to RA.

Conclusion: ETN treatment was more effective than CYC treatment, and CRP, albumin and eGFR may be valuable biomarkers for analysis. The SAA1.3 allele was not a factor affecting treatment in Japanese patients with AA amyloidosis secondary to RA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyloidosis / drug therapy*
  • Amyloidosis / etiology
  • Amyloidosis / genetics
  • Arthritis, Rheumatoid / complications*
  • Cause of Death
  • Cyclophosphamide / therapeutic use*
  • Etanercept
  • Female
  • Genotype
  • Glomerular Filtration Rate / physiology
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / etiology
  • Kidney Diseases / genetics
  • Male
  • Polymorphism, Genetic / genetics
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Retrospective Studies
  • Serum Amyloid A Protein / genetics*
  • Treatment Outcome


  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Serum Amyloid A Protein
  • Cyclophosphamide
  • Etanercept