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Efficacy of cyclophosphamide combined with prednisolone in patients with AA amyloidosis secondary to rheumatoid arthritis

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Abstract

Secondary amyloid A (AA) amyloidosis is an uncommon yet important complication of rheumatoid arthritis (RA). It is one of the most relentless of the extra-articular features of RA, and suitable treatments have not yet been found. We studied the efficacy of cyclophosphamide (CYC) combined with prednisolone (PSL) in amyloidotic patients who had serum amyloid A (SAA) 1.3 genotype, which is a risk factor for secondary amyloidosis in Japanese RA patients. Fifteen RA patients who were SAA1.3 homo- and heterozygotes with biopsy-confirmed AA amyloidosis were treated with a combination of CYC and PSL. Laboratory variables of C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), serum albumin (Alb), serum creatinine (Cre) and Lansbury’s index were carried out by statistical analysis of changes between before and during the medication. According to the Mann–Whitney rank test, CRP, RF, ESR, Alb and Cre levels improved significantly with the combination treatment (p<0.05). Also, paired t-tests showed significance in Lansbury’s index between before and during the medication (p=0.007). CYC combined with PSL ameliorated not only laboratory markers but also clinical rheumatoid activity in patients with amyloidosis secondary to RA, whose genotypes were SAA1.3 homo- and heterozygous. CRP, ESR, RF, Alb and Cre will be surrogate markers of therapeutic efficacy. The combination of CYC and PSL appears to be beneficial for Japanese RA patients who are SAA1.3 homo- and heterozygous carriers, associated with secondary AA amyloidosis.

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Abbreviations

AA:

Amyloid A

CRP:

C-reactive protein

Ccr:

Creatinine clearance

CYC:

Cyclophosphamide

DMARD:

Disease-modifying antirheumatic drugs

ESR:

Erythrocyte sedimentation rate

NSAID:

Non-steroidal anti-inflammatory drugs

PCR:

Polymerase chain reaction

PSL:

Prednisolone

RA:

Rheumatoid arthritis

RF:

Rheumatoid factor

SAA:

Serum amyloid A

References

  1. Baba S, Masago SA, Takahashi T et al. (1995) A novel allelic variant of serum amyloid A, SAA1γ: genomic evidence, evolution, frequency, and implication as a risk factor for reactive systemic AA-amyloidosis. Hum Mol Genet 4:1083–1087

    CAS  PubMed  Google Scholar 

  2. Baba S, Miyamoto S, Kawashima M et al. (1999) Serum amyloid A gene polymorphism and AA-amyloidosis. In: Kyle RA, Gertz MA, eds. Amyloid and amyloidosis. New York, Parthenon Publishing Group, :417–419

  3. Cunnane G (2001) Amyloid precursors and amyloidosis in inflammatory arthritis. Cur Opin Rheumatol 13:67–73

    Article  CAS  Google Scholar 

  4. Gillmore JO, Levitt LB, Jersey MA, Pepys MB, Hawkins PN (2001) Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein. Lancet 358:24–29

    Article  CAS  PubMed  Google Scholar 

  5. Joss N, McLaughlin K. Simpson K, Boulton-Jones JAM (2000) Presentation, survival and prognostic markers in AA amyloidosis. Q J Med 93:535–542

    Article  CAS  Google Scholar 

  6. Ahlmen M, Ahlmen J, Svalander C, Bucht H (1987) Cytotoxic drug treatment of reactive amyloidosis in rheumatoid arthritis with special reference to renal insufficiency. Clin Rheumatol 6:27–38

    CAS  Google Scholar 

  7. Berglund K, Thysell H, Keller C (1993) Results, principles and pitfalls in the management of renal AA-amyloidosis; a 10–21 year followup of 16 patients with rheumatic disease treated with alkylating cytostatics. J Rheumatol 20:2051–2057

    CAS  PubMed  Google Scholar 

  8. Savolainen HA (1999) Chlorambucil in severe juvenile chronic arthritis: longterm followup with special reference to amyloidosis. J Rheumatol 26:898–903

    CAS  PubMed  Google Scholar 

  9. Nakamura T, Baba S, Yamamura Y et al. (2000) Combined treatment with cyclophosphamide and prednisolone is effective for secondary amyloidosis with SAA1γ/γ genotype in a patient with rheumatoid arthritis. Mod Rheumatol 10:160–164

    Article  Google Scholar 

  10. Arnett FC, Edworthy SM, Bloch DA et al. (1988) The American Rheumatism Association 1987 revised criteria for classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    CAS  PubMed  Google Scholar 

  11. Lansbury J (1977) The pooled index. J Rheumatol 4:445–446

    CAS  PubMed  Google Scholar 

  12. Steinbrocker O, Traeger CH, Batterman RC (1949) Therapeutic criteria in rheumatoid arthritis. JAMA 140:659–662

    Google Scholar 

  13. Falck HM, Tornroth T, Skrifvars B, Wegelius O (1979) Resolution of renal amyloidosis secondary to rheumatoid arthritis. Acta Med Scand 205:651–656

    CAS  PubMed  Google Scholar 

  14. Berglund K, Keller C, Thysell H (1987) Alkylating cytostatic treatment in renal amyloidosis secondary to rheumatoid arthritis. Ann Rheum Dis 46:757–762

    CAS  PubMed  Google Scholar 

  15. Horslev-Petersen K, Beyer JM, Helin P (1983) Intermittent cyclophosphamide in refractory rheumatoid arthritis. Br Med J 287:711–712

    CAS  Google Scholar 

  16. Keysser G, Keysser C, Keysser M (1998) Treatment of refractory rheumatoid arthritis with low-dose cyclophosphamide. Long-term follow-up of 108 patients. Z Rheumatol 57:101–107

    Article  CAS  Google Scholar 

  17. Deschenes G, Prieur AM, Hayem F, Broyer A, Gubler MC (1990) Renal amyloidosis in juvenile chronic arthritis: evolution after chlorambucil treatment. Pediatr Nephrol 4:463–469

    CAS  PubMed  Google Scholar 

  18. David J, Vouyiouka O, Ansell BM, Hall A, Woo P (1993) Amyloidosis in juvenile chronic arthritis: a morbidity and mortality study. Clin Exp Rheumatol 2:85–90

    Google Scholar 

  19. Gertz MA, Kyle RA (1991) Secondary systemic amyloidosis: response and survival in 64 patients. Medicine 70:246–256

    CAS  PubMed  Google Scholar 

  20. Maezawa A, Hiromura K, Mitsuhashi H et al. (1994) Combined treatment with cyclophosphamide and prednisolone can induce remission of nephritic syndrome in a patient with renal amyloidosis, associated with rheumatoid arthritis. Clin Nephrol 42:30–32

    CAS  PubMed  Google Scholar 

  21. Gomez-Casanovas E, Sanmarti R, Sole M, Canate JD, Munoz-Gomez J (2001) The clinical significance of amyloid fat deposits in rheumatoid arthritis. A systematic long-term followup study using abdominal fat aspiration. Arthritis Rheum 44:66–72

    Article  CAS  PubMed  Google Scholar 

  22. Chevrel G, Jenvrin C, McGregor B, Miossec P (2001) Renal type AA amyloidosis associated with rheumatoid arthritis: a cohort study showing improved survival on treatment with pulse cyclophosphamide. Rheumatology 40:821–825

    Article  CAS  PubMed  Google Scholar 

  23. Rochen C, Shakespeare A (2002) Pathology, diagnosis and pathogenesis of AA amyloidosis. Virchows Arch 440:111–122

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Dr Laurence A. Boxer, Professor, Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, MI, USA, for his editorial advice on the manuscript. This work was supported in part by a grant-in-aid for scientific research from the Japanese Ministry of Education, Science, Sports, and Culture.

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Authors and Affiliations

  1. Kumamoto Center for Arthritis and Rheumatology, 1-15-7 Kuhonji, 862-0976, Kumamoto, Japan

    Tadashi Nakamura, Yuji Yamamura, Kunihiko Tomoda & Michishi Tsukano

  2. Kumamoto University School of Medicine, 2-2-1 Honjo, 860-0811, Kumamoto, Japan

    Masahiro Shono

  3. Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Shizuoka, Japan

    Satoshi Baba

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  1. Tadashi Nakamura
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  2. Yuji Yamamura
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  3. Kunihiko Tomoda
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  4. Michishi Tsukano
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  5. Masahiro Shono
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  6. Satoshi Baba
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Correspondence to Tadashi Nakamura.

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Nakamura, T., Yamamura, Y., Tomoda, K. et al. Efficacy of cyclophosphamide combined with prednisolone in patients with AA amyloidosis secondary to rheumatoid arthritis. Clin Rheumatol 22, 371–375 (2003). https://doi.org/10.1007/s10067-003-0763-9

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  • DOI: https://doi.org/10.1007/s10067-003-0763-9

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