A case with rheumatoid arthritis and systemic reactive AA amyloidosis showing rapid regression of amyloid deposition on gastroduodenal mucosa after a combined therapy of corticosteroid and etanercept

Previous histochemical studies have suggested a close temporal relationship between the deposition of highly sulfated glycosaminoglycans (GAGs) and amyloid during experimental AA amyloidosis. In the present investigation, we extended these initial observations by using specific immunocytochemical probes to analyze the temporal and ultrastructural relationship between heparan sulfate proteoglycan (HSPG) accumulation and amyloid deposition in a mouse model of AA amyloidosis. Antibodies against the basement membrane-derived HSPG (either protein core or GAG chains) demonstrated a virtually concurrent deposition of HSPGs and amyloid in specific tissue sites regardless of the organ involved (spleen or liver) or the induction protocol used (amyloid enhancing factor + silver nitrate, or daily azocasein injections). Polyclonal antibodies to AA amyloid protein and amyloid P component also demonstrated co-localization to sites of HSPG deposition in amyloid sites, whereas no positive immunostaining was observed in these locales with a polyclonal antibody to the protein core of a dermatan sulfate proteoglycan (known as "decorin"). Immunogold labeling of HSPGs (either protein core or GAG chains) in amyloidotic mouse spleen or liver revealed specific localization of HSPGs to amyloid fibrils. In the liver, heparan sulfate GAGs were also immunolocalized to the lysosomal compartment of hepatocytes and/or Kupffer cells adjacent to sites of amyloid deposition, suggesting that these cells are involved in HSPG production and/or degradation. The close temporal and ultrastructural relationship between HSPGs and AA amyloid further implies an important role for HSPGs during the initial stages of AA amyloidosis.

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FRI0116 COMPARABLE EFFICACY AND SAFETY OF TWO REGIMENS OF RHEUMATOID ARTHRITIS TREATMENT WITH TOFACITINIB: DATA FROM RUSSIAN NATIONAL REGISTRY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3662 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 639-639

Author(s):

A. Babaeva ◽

E. Kalinina ◽

E. Nasonov ◽

V. Mazurov ◽

G. Lukina ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Therapy Group ◽

Target Therapy ◽

Combined Therapy ◽

National Registry ◽

Comparable Efficacy ◽

Efficacy And Safety ◽

National Guidelines ◽

Therapy Regimen ◽

Conventional Dmards

Background:Current EULAR and national guidelines recommend use of synthetic target drug Tofacitinib (TOFA) for active rheumatoid arthritis (RA) treatment in case of resistance or intolerance to metotrexate (MTX) or other conventional DMARDs. Two treatment regimens are approved: TOFA mono-therapy and combination with conventional DMARD, preferably with MTX.Objectives:Aim of presented study was to compare efficacy and safety of TOFA given in two regimens: as mono-therapy and in combination with MTX.Methods:We analyzed data from Russian national registry of RA. 450 patients (pts) treated with TOFA in dose 10 mg daily have been enrolled in this investigation. Among them 169 pts have composed TOFA mono-therapy group (mono) and 281 pts treated with TOFA plus MTX have been included in combo-therapy group (combo). Period of treatment varied from 6 months to 3 years and even more. Treatment efficacy was evaluated on the basis of clinical and laboratory indices of RA activity: CDAI, SDAI, DAS28, HAQ, GPA (general pain assessment), TJC, SJC, CRP, ESR monthly during first 6 months, than in 1,2,3 years and after 3 year period of treatment.Results:There were no significant differences in pts demographic characteristic and disease longevity and/or severity in two separated groups. Majority of baseline indices were identical in these groups aside from SDAI, CRP (were higher in combo-group) and HAQ (was higher in mono-group). Pts monitoring have shown dramatically decrease of all used indices during the first several months of therapy in both groups. Moreover all clinical and laboratory parameters after 6-months treatment were comparable in mono- and combo- groups. Positive dynamics remained during further 3-year period in both groups. Significant differences between baseline and ultimate data after 3 year course therapy were revealed in CDAI, SDAI, DAS28, HAQ, GPA, TJC, SJC, CRP, ESR in both groups. In particular DAS28 index decreased from 5.38±0.08 to 2.88±0.07 (p<0.05) in mono-group and from 5.54±0.09 to 3.40±0.21 (p<0.05) in combo-group. Along with this comparing of endpoints in two analyzed groups have shown that levels of CDAI, SDAI, GPA were significant higher in combo-group than in mono-group (p<0.05). Adverse effects were registered in 4.73% pts from mono-group and in 4.98% pts from combo-group (p>0.05). Spectrum of adverse reactions was similar in compared groups: respiratory infection (in 2.96% and 3.36% cases respectively) and herpes infection (in 0.59% and 0.71% cases, respectively) were registered predominantly.Conclusion:Data gained from National RA registry have demonstrated that treatment with TOFA in mono-therapy regimen has the comparable efficacy with regimen of combined therapy, included MTX and TOFA. Safety of both regimens can be qualified as good. Obtained results confirm high efficacy and safety of target therapy with TOFA and prove the recommendation for use it in different regimens – mono-therapy or combination with MTX.References:[1]Smolen JS, et al. Ann Rheum Dis. 2017;0:1–18. doi:10.1136/annrheumdis-2016-210715[2]Boyle DL, et al. Ann Rheum Dis. 2015;74:1311-1316. doi:10.1136/annrheumdis-2014-206028Disclosure of Interests:Aida Babaeva: None declared, Elena Kalinina: None declared, Evgeny Nasonov Speakers bureau: Lilly, AbbVie, Pfizer, Biocad, R-Pharm, V Mazurov: None declared, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Antonina Davydova: None declared, Irina Semizarova: None declared, Olga Slyusar: None declared, Tatyana Rasevich: None declared, Ruzana Samigullina: None declared, Diana Abdulganieva: None declared

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THU0294 Co-Existent Major Complications (Vasculitis, AA Amyloidosis, Lethal Septic Infection and Purulent Arthritis) in Rheumatoid Arthritis – A Retrospective Clinicopathologic-Statistical Study of 161 Autopsy Patients:

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2014-eular.2329 ◽

2014 ◽

Vol 73 (Suppl 2) ◽

pp. 284.4-285

Author(s):

M. Bély ◽

Ά. Apáthy

Keyword(s):

Rheumatoid Arthritis ◽

Statistical Study ◽

Aa Amyloidosis ◽

Major Complications

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Rituximab Therapy in Renal Amyloidosis Secondary to Rheumatoid Arthritis

Biomolecules ◽

10.3390/biom8040136 ◽

2018 ◽

Vol 8 (4) ◽

pp. 136 ◽

Cited By ~ 3

Author(s):

Levent Kilic ◽

Abdulsamet Erden ◽

Yusuf Sener ◽

Berkan Armagan ◽

Alper Sari ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Improvement ◽

Inflammatory Diseases ◽

Case Series ◽

New Drugs ◽

Renal Amyloidosis ◽

Secondary Amyloidosis ◽

Aa Amyloidosis ◽

Amyloid A ◽

Significant Clinical Improvement

Secondary amyloid A (AA) amyloidosis is a late and serious complication of poorly controlled, chronic inflammatory diseases. Rheumatoid arthritis (RA) patients with poorly controlled, longstanding disease and those with extra-articular manifestations are under risk for the development of AA amyloidosis. Although new drugs have proven to be significantly effective in the treatment of secondary AA amyloidosis, no treatment modality has proven to be ideal. To date, only in small case series preliminary clinical improvement have been shown with rituximab therapy for AA amyloidosis secondary to RA that is refractory to TNF-α inhibitors (TNF-i) therapy. In these case series, we assessed the efficacy and safety of rituximab therapy for patients with RA and secondary amyloidosis. Hacettepe University Biologic Registry was developed at 2005. The data of the RA patients who were prescribed a biological drug were recorded regularly. Patients with biopsy proven AA amyloidosis patients were screened. Of 1022 RA patients under biologic therapy, 0.7% patients had clinically apparent histologically confirmed amyloidosis. Four of seven patients who were prescribed rituximab at least one infusion enrolled to those case series. Two of four patients showed significant clinical improvement and one of them also had decrease in proteinuria and the other one had stable renal function and proteinuria. The main goal for the treatment of AA amyloidosis is to control the activity of the underlying disorder. In this study, we showed that rituximab may be an effective treatment in RA patients with amyloidosis who were unresponsive to conventional disease modifying anti-rheumatic drugs (DMARDs) and/or TNFi.

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Deposition, Clearance, and Reinduction of Amyloid A Amyloid in Interleukin 1 Receptor Antagonist Knockout Mice

Veterinary Pathology ◽

10.1177/0300985816658772 ◽

2016 ◽

Vol 54 (1) ◽

pp. 99-110 ◽

Cited By ~ 4

Author(s):

K. Watanabe ◽

K. Uchida ◽

J. K. Chambers ◽

N. Ushio ◽

H. Nakayama

Keyword(s):

Receptor Antagonist ◽

Knockout Mice ◽

Interleukin 1 ◽

Recovery Process ◽

Amyloid Deposition ◽

Aa Amyloidosis ◽

Amyloid A ◽

Enhancing Factor ◽

Amyloid Deposits ◽

Amyloid Enhancing Factor

Amyloid A (AA) amyloidosis is characterized by the extracellular deposition of AA amyloid and results in the irreversible dysfunction of parenchymal organs. In experimental models, AA amyloid deposits are cleared following a decrease in circulating serum amyloid A (SAA) concentrations. Additional inflammatory stimuli during this recovery process may induce more severe amyloid redeposition. In the present study, we confirmed the deposition, clearance, and reinduction of AA amyloid deposits in interleukin 1 receptor antagonist knockout mice (IL-1raKO) and studied the SAA levels and amyloid-enhancing factor activity based on the time-dependent changes of amyloid deposition. Histopathologically, following initial (day 0) injection of amyloid-enhancing factor in combination with an inflammatory stimulus (silver nitrate [AgNO3]), amyloid deposition peaked by day 20, and its deposition gradually decreased after day 35. SAA concentrations in serum were precipitously elevated on day 1 but returned to normal levels by day 10, whereas the SAA dimer was detected in serum after day 45. An additional AgNO3 injection was administered to mice with amyloidosis on day 5, 10, 35, or 50, and all mice developed large amyloid deposits. Amyloid deposition was most severe in mice treated with AgNO3 on day 35. The inoculation of sera from mice with AA amyloidosis, combined with AgNO3, induced AA amyloidosis. Serum samples collected on days 35 and 50, which contained high concentrations of the SAA dimer, induced amyloidosis in a high proportion (83%) of mice. Therefore, increased SAA and/or its dimer in serum during the recovery process may markedly exacerbate the development of AA amyloidosis.

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