Background Systemic AA-amyloidosis is a severe complication of RA occurring due to upregulated production of serum amyloid A (SAA), induced predominantly by IL-6.
Objectives To assess Tocilizumab (humanized monoclonal antibody to IL-6 receptors) impact on kinetics of treatment target parameters in sysemic nephrotic type AA-amyloidosis, secondary to RA.
Methods DAS28, SAA levels, CRP, ESR, 24-hour proteinuria, glomerular filtration (GFR), and gistomorphologic examination of biopsy samples were monitored in all participants to the study in addition to the standard clinical and lab parameters. Statistical processing covered the number of participating subjects, arithmetic mean (AM), standard deviation from AM (δ). Difefferces were considered statistically significant with p values <0,05. Student's t-test was used. Data was processed with Statistica 7.0 for Windows (“StatSoft Inc.”) software.
Results The study included 10 pts (mean age 52±9,1 y.) with systemic AA amiloidosis and morphologically verified nephrotic syndrome (biosy samples of duodenal mucous), secondary to RA, meeting ACR 1987 criteria (average disease duration - 17,1±8,9 y). All poor responders to DMARDs, NSAIDs and GCs at a stable dose for at minimum 6 preceding mo (peroral <10 mg/day prednisolone or its equivalent) were administered Tocilizumab i/v by drop infusions each 4 weeks at 8 mg/kg during total 12 mo.
After 12 mo of therapy significant decrease was documented for mean SAA (from 46,7±28,1 mg/mL to 14,7±24,3 mg/mL; p=0,03), DAS28 score (from 5,5±1,4 to 3,3±1,15; p=0,003), 24-hour proteinuria (from 0,8±0,7 g/day to 0,08±0,6 g/day; p=0,04). At the same time no desiarable changes occurred in ESR (from 32,1±19,5 mm/hour to 17±26,5 mm/hour; p=0,1), GFR (from 62,2±42,9 mL/min to 54,2±31,9 mL/min; p=0,3). Although, second control biopsy& histomorphology did not reveal amiloid depositions in duodenal mucous in 2 pts.
Conclusions 12-mo Tocilizumab therapy resulted in target decrease of RA activity, accompanied by simultaneous decrease in SAA and 24-hour pronteinuria (although not all pts achieved the desired target levels), and complete disappearance of amiloid depositions in duodenal mucous in 2 pts.
Lane T, Gillmore JD, Wechalekar AD, ey al. Therapeutic blockade of interleukin-6 by tocilizumab in the management of AA amyloidosis and chronic inflammatory disorders: a case series and review of the literature. Clin Exp Rheumatol. 2015 Nov-Dec;33(6 Suppl 94):S46–53.
Disclosure of Interest None declared