Optimal Treatment Strategy for Amyloid A Amyloidosis in Rheumatic Diseases – Anti-Interleukin-6 Receptor Therapy

Abstract

Among the complications of inflammatory rheumatic diseases, amyloid A (AA) amyloidosis is one of the most severe because of its poor prognosis. AA amyloidosis commonly affects the kidney and the gastrointestinal tract, and is characterized by various clinical symptoms such as progressive proteinuria and renal dysfunction and failure. Control of the underlying disease, i.e. suppression of serum amyloid A (SAA) levels, is the most critical step in the treatment of AA amyloidosis. An immunosuppressant such as methotrexate, azathioprine, or cyclophosphamide, and moderate doses of prednisolone are commonly used to accomplish this. However, in some active cases, satisfactory suppression of SAA levels cannot be achieved, and the function of the affected organs deteriorates. The prognosis is usually poor for patients in advanced stages of AA amyloidosis. The major causes of death are renal failure and infection. Some retrospective studies and case reports have shown antitumor necrosis factor (TNF) therapies to be useful against AA amyloidosis (Elkayam et al., 2002; Fernandes-Nebro et al., 2010; Gottenberg et al., 2003; Kuroda et al., 2009; Nakamura et al., 2010). Although treatment with anti-TNF agents does reduce acute-phase reactants such as C-reactive protein (CRP) and SAA in chronic inflammatory diseases, unfortunately complete normalization of such acute-phase proteins is rarely observed. On the other hand, several case reports and a retrospective comparative study have shown that tocilizumab, an anti-human interleukin-6 (IL-6) receptor monoclonal antibody, has an excellent ability to suppress SAA levels and improve clinical symptoms of AA amyloidosis with marked lasting regression of AA protein deposits (Inoue et al., 2010; Kishida et al., 2011; Nishida et al., 2009; Okuda & Takasugi, 2006; Okuda 2009; Sato et al., 2009; Ubara, 2009). Treatment with tocilizumab could, therefore, represent an important therapeutic strategy for AA amyloidosis secondary to rheumatic diseases.