Tuesday, January 28, 2014

Treatment of secondary amyloid

Recently I've been dealing with an unfortunate individual with a long history of RA who has developed nephrotic range proteinuria after being stable for many years. Despite the deteriorating renal function, NSAIDs have been continued because without them the patient has no quality of life. Biologics were tried in the past with very severe adverse effects and so we are reduced to treating this much the same as it was treated many years ago. Recently, a review in Nature Reviews Nephrology summarized the most up-to-date thinking on the treatment of systemic amyloid. Similar to my patient, about 50% of patients with AA amyloid have nephrotic syndrome and ~10% have ESRD at diagnosis. More than 40% of patients with AA amyloid eventually progress to ESRD.

For AA amyloid, the primary goal of treatment is to suppress the underlying inflammatory disease and hence prevent further amyloid production.

1. Colchicine: Colchicine has been shown to be effective in the treatment of Familial Mediterranean Fever in particular. It is used as a prophylactic agent to prevent the development of renal amyloid and, in higher doses, can be used to treat nephrotic syndrome although care must be used in patients with decreased renal function. There is less evidence for its effectiveness in rheumatoid diseases.

2. DMSO: This has been shown in small studies to be effective in treating secondary amyloid and in murine studies. However, in one study, there was no effect in patients who had already developed significant renal dysfunction.

3. Cytotoxic Therapy: Cyclophosphamide has been shown to have some effect in AA amyloid in small cases series and retrospective studies. There are no RCTs available. One recent study compared cyclophosphamide with etanercept and found that there was a far higher response rate with etanercept. However, this was a small study and was not an RCT so it is difficult to fully draw conclusions. Methotrexate, chlorambucil and axathioprine have also been shown to have some effect.

4. Anticytokine Therapy: This is currently probably the gold standard of treatment. Anti-TNF treatments has been shown to be effective in preventing the development of AA amyloid and even reversing established disease. More recently, in a small retrospective study, toclizumab, a new IL-6 antagonist was shown to be more effective than TNF antagonists in the treatment of AA amyloid. Other anti-cytokine therapies are being tested for their effectiveness in treating secondary amyloid and this is a field that is advancing rapidly.

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