Correspondence

Eprodisate in AA Amyloidosis

N Engl J Med 2007; 357:1153-1154September 13, 2007

Article

To the Editor:

Dember et al. (June 7 issue)1 report that eprodisate slows the deterioration of renal function in patients with AA amyloidosis. However, they do not mention the use of colchicine in patients with familial Mediterranean fever–related AA amyloidosis (19% of their study population). In a related article, Lachmann et al.2 report that patients with AA amyloidosis associated with familial Mediterranean fever were treated with colchicine. The beneficial effects of colchicine in these patients have led to its use for amyloidosis secondary to other causes, which is why we believe that colchicine therapy was probably also given to a number of patients without familial Mediterranean fever–related AA amyloidosis in both studies. It is important to consider the use of colchicine when amyloid kidney disease progresses. Colchicine can prevent the deterioration of kidney function in patients with familial Mediterranean fever–related AA amyloidosis,3 and it has an antifibrotic effect on the interstitial fibrosis of renal allografts.4

Lucio Manenti, M.D.
Pius Tansinda, M.D.
Arcispedale Santa Maria Nuova, 42100 Reggio Emilia, Italy
lucio.manenti@asmn.re.it

Augusto Vaglio, M.D.
Università di Parma, 43100 Parma, Italy

4 References

1. 1

   Dember LM, Hawkins PN, Hazenberg BPC, et al. Eprodisate for the treatment of renal disease in AA amyloidosis. N Engl J Med 2007;356:2349-2360
   Full Text | Web of Science | Medline

2. 2

   Lachmann HJ, Goodman HJB, Gilbertson JA, et al. Natural history and outcome in systemic AA amyloidosis. N Engl J Med 2007;356:2361-2371
   Full Text | Web of Science | Medline

3. 3

   Cakar N, Yalcinkaya F, Ozkaya N, et al. Familial Mediterranean fever (FMF)-associated amyloidosis in childhood: clinical features, course and outcome. Clin Exp Rheumatol 2001;19:Suppl 24:S63-S67
   Web of Science | Medline

4. 4

   Ozdemir BH, Ozdemir FN, Sezer S, Sar A, Haberal M. Does colchicine have an antifibrotic effect on development of interstitial fibrosis in renal allografts of recipients with familial Mediterranean fever? Transplant Proc 2006;38:473-476
   CrossRef | Web of Science | Medline

Author/Editor Response

We agree that by reducing the inflammation of familial Mediterranean fever, colchicine can prevent or retard AA amyloidosis.1 In our trial of eprodisate for patients with AA amyloidosis, all the patients with familial Mediterranean fever (15 in the eprodisate group and 20 in the placebo group) received treatment with colchicine. Twenty-two patients with diseases other than familial Mediterranean fever also received colchicine; thus, the total number of patients treated with colchicine was 22 (25%) in the eprodisate group and 35 (37%) in the placebo group (P=0.08 for the difference between the two groups). The reduction in the risk of worsening renal disease or death (the composite primary end point of the trial) associated with eprodisate treatment persisted after adjustment for the baseline use of colchicine (unadjusted hazard ratio, 0.58; 95% confidence interval [CI], 0.37 to 0.93; P=0.02; adjusted hazard ratio, 0.56; 95% CI, 0.35 to 0.90; P=0.02). Furthermore, there was no evidence of an interaction between colchicine and eprodisate (P=0.68 in the Cox proportional-hazards model that included eprodisate, colchicine, and their interaction, stratified according to baseline nephrotic status), indicating that eprodisate had similar benefits for patients who received colchicine and patients who did not receive colchicine. Thus, the observed differences in outcomes in the two treatment groups were not due to differential use of colchicine.

Laura M. Dember, M.D.
Boston University School of Medicine, Boston, MA 02118
ldember@bu.edu

Robert Balshaw, Ph.D.
University of British Columbia, Vancouver, BC V6T 1Z4, Canada

1 References

1. 1

   Zemer D, Pras M, Sohar E, Modan M, Cabili S, Gafni J. Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. N Engl J Med 1986;314:1001-1005
   Full Text | Web of Science | Medline

Author/Editor Response

Manenti and colleagues incorrectly deduced that in our study, patients with AA amyloidosis associated with diseases other than familial Mediterranean fever were likely to have been treated with colchicine. Colchicine is of singular benefit in patients with AA amyloidosis associated with familial Mediterranean fever because it greatly suppresses this particular chronic inflammatory disease. Their suggestion that colchicine might be beneficial in kidney disease due to other mechanisms of action is not supported by the similar renal outcomes among the 20 patients with familial Mediterranean fever who received colchicine and the other 354 patients with other underlying inflammatory diseases who did not (relative risk of end-stage renal failure in the patients with familial Mediterranean fever, 1.51; 95% CI, 0.61 to 3.75; P=0.37). Furthermore, treatment with colchicine has the potential for severe toxic effects, the risk of which is increased in the presence of renal impairment. Even modest doses can cause diarrhea or vomiting that may precipitate irreversible end-stage renal failure in patients with amyloidosis.

Helen J. Lachmann, M.D.
Philip N. Hawkins, Ph.D., F.Med.Sci.
Royal Free and University College Medical School, London NW3 P2F, United Kingdom

Citing Articles (1)

Citing Articles

1. 1

   Michael J. Hausmann, Esther Maor, Leonid Kachko. (2011) Colchicine-sensitive nephrotic syndrome due to AA amyloidosis. Amyloid 18:3, 169-171
   CrossRef