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BOURGUIBA Rim

Anti-proinflammatory cytokine biotherapy can prevent the progression of AA amyloidosis to end-stage renal disease.

Updated: Sep 24

First author: Kvacskay P

Revue : Annals of Rheumatic disease

Reference:  PMID: 38653531 ; DOI: 10.1136/ard-2023-225114


 

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 amyloidosis were identified and followed for a mean observation period of 4.82 years.

The patients were 34 with cid+AA (40.5%), including 18 with rheumatoid arthritis and 8 with chronic inflammatory bowel disease; 25 with idio+AA (30.5%) and 24 with auto+AA (29%), including 22 with familial Mediterranean fever and 2 with cryopyrinopathies.

Levels of C-reactive protein (CRP), serum amyloid A protein (SAA) and proteinuria were significantly reduced under treatment with biotherapy.

With biotherapy, progression to ESRD was prevented in 88% of patients in the auto+AA group, 81% in the idio+AA group and 60% in the cid+AA group during the study period.

Thirty-four patients received tocilizumab in the cid+AA (n=18) and idio+AA (n=16) arms. Tocilizumab was more effective in reducing CRP and progression to ESRD and death than other biotherapies. No patient taking tocilizumab during the study period died.

Patients with autoinflammatory diseases were excluded from this analysis with tocilizumab as this biotherapy is not indicated for inflammatory diseases.


Conclusion


Anti-proinflammatory cytokine biotherapies reduce systemic inflammation in various diseases associated with the development of AA amyloidosis, leading to a reduction in proteinuria and prevention of ESRD.


In this retrospective series, tocilizumab tested in 34 patients with AA amyloidosis complicating chronic or idiopathic inflammatory disease was more effective than other biotherapies in controlling systemic inflammation, leading to improved renal and overall survival in these patients.


Figures


Figure 1. Serum biomarkers and proteinuria are analysed in subgroups of AA patients with chronic inflammatory disease cid+AA (cid+AA), autoinflammatory disease auto+AA (auto+AA) and idiopathic disease (idio+AA).


Biotherapy was initiated at the first visit (baseline) and compared with the last documented visit 4 to 6 years later. CRP (A), SAA (B), serum creatinine (C), sample proteinuria (D), serum albumin (E), total serum protein (F), serum IgG (G) and NT-BNP (H) were analysed at the first and last visits.

Figure 1


Figure 2: Patients treated with Tocilizumab (TOC) were compared with other biotherapies.


(A): Patients with cid+AA (cid+AA) and idio+AA were followed every 6 months until the last visit.

(B) and (C): Analyses of cid+AA (cid+AA) and idio+AA subgroups are shown. (D) Across the cohort tocilizumab (TOC) prevented progression of AA to other organs and death (D).


Figure 2


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