bDMARD can prevent the progression of AA amyloidosis to end-stage renal disease

Abstract

Introduction: AA amyloidosis (AA) can be the consequence of any chronic inflammatory disease. AA is associated with chronic inflammatory diseases (cid+AA), autoinflammatory syndromes (auto+AA) or AA of unknown origin or idiopathic AA (idio+AA). The major organ manifestation is renal AA that can progress to end-stage renal disease (ESRD) and multiple organ failure.

Materials and methods: This study is a monocentric retrospective analysis of the renal outcome and survival of patients with cid+AA (n=34), auto+AA (n=24) and idio+AA (n=25) who were treated with cytokine-inhibiting biological disease-modifying antirheumatic drugs (bDMARDs).

Results: 83 patients with renal AA were identified and followed for a mean observational period of 4.82 years. C reactive protein (CRP), serum amyloid alpha and proteinuria were significantly reduced with bDMARD therapy. Progression to ESRD was prevented in 60% (cid+AA), 88% (auto+AA) and 81% (idio+AA) of patients. Tocilizumab was given to 34 patients with cid+AA and idio+AA and was more effective in reducing CRP and progression to ESRD and death compared with other bDMARDs.

Conclusions: bDMARDs reduce systemic inflammation in various diseases, leading to a reduction of proteinuria and prevention of ESRD. Importantly, tocilizumab was more effective than other bDMARDs in controlling systemic inflammation in patients with chronic inflammatory diseases and idiopathic AA, leading to better renal and overall survival.

Keywords: Amyloidosis; Autoimmune Diseases; Biological Therapy; Familial Mediterranean Fever; Therapeutics.

Figure 1. Serum biomarkers and proteinuria were analysed in AA patient subgroups with chronic inflammatory disease (cid+AA), autoinflammatory disease (auto+AA) and idiopathic (idio+AA). bDMARD treatment was initiated at the first visit (baseline) and compared with the last documented visit 4–6 years later. C reactive protein (CRP) (A), serum amyloid alpha (SAA) (B), serum creatinine (C), proteinuria on spot urine (D), serum albumin (E), total serum protein (F), serum IgG (G) and N-terminal brain natriuretic peptide (NT-BNP) (H) were analysed at the first and last visit. AA, AA amyloidosis; bDMARD, biological disease-modifying antirheumatic drug.

Figure 2. Serum creatinine and spot proteinuria were analysed in the total cohort (A, B) and in the AA subgroups with different aetiologies (C–H). Serum creatinine and proteinuria were normalised with the values at the first visit. Reappointments were scheduled every 6 months. Patients with a preserved renal function (circles) were compared with patients with ESRD at the last visit (squares). AA, AA amyloidosis; auto+AA, patients with an autoinflammatory syndrome and AA amyloidosis; cid+AA, patients with chronic inflammatory diseases and AA amyloidosis; ESRD, end-stage renal disease; idio+AA, patients with idiopathic AA amyloidosis.

Figure 3. Patients with TOC treatment were compared with other bDMARD treatment. Patients with cid+AA and idio+AA were followed every 6 months until the last visit (A). Subgroup analyses of cid+AA (B) and idio+AA (C) are indicated. In the whole cohort, TOC treatment prevented the progression of AA to other organs and death (D). AA, AA amyloidosis; bDMARD, biological disease-modifying antirheumatic drug; cid+AA, patients with chronic inflammatory diseases and AA amyloidosis; ESRD, end-stage renal disease; TOC, tocilizumab; idio+AA, patients with idiopathic AA amyloidosis.