Long term administration of tocilizumab improves renal amyloid A (AA) amyloidosis deposition in Familial Mediterranean fever

We aimed to explore triggering receptor expressed on myeloid cells-1 (TREM-1) activation in familial Mediterranean fever (FMF), the most frequent monogenic auto-inflammatory disease, through the measurement of its serum soluble form, named sTREM-1. Blood samples from patients with FMF according to Livneh criteria followed in the French FMF national center and carrying two pathogenic MEFV mutations were collected. Serum level of sTREM-1 was assessed using ELISA. Demographic data, presence of FMF attack, association with histologically proven AA amyloidosis, and blood levels of C-reactive protein (CRP), serum amyloid A (SAA) protein, and creatinine were collected. TREM-1 was available in 56 patients (33.9% male, mean age 43 yr); AA amyloidosis was associated in six patients (19.6% in FMF). Mean sTREM-1 level did not differ significantly between patients having an attack or not and there was also no significant correlation between the level of sTREM-1 and CRP and SAA protein. However, the mean rate of sTREM-1 was significantly higher among FMF patients with AA amyloidosis versus without, though the concomitant SAA protein level was normal. Serum level of sTREM-1 was higher in patients with amyloidosis even though the concomitant SAA protein level was normal. sTREM-1 plasma levels could be an accurate tool to specifically identify FMF patients with amyloidosis.

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Amyloidosis and Glomerular Diseases in Familial Mediterranean Fever

Medicina ◽

10.3390/medicina57101049 ◽

2021 ◽

Vol 57 (10) ◽

pp. 1049

Author(s):

Rossella Siligato ◽

Guido Gembillo ◽

Vincenzo Calabrese ◽

Giovanni Conti ◽

Domenico Santoro

Keyword(s):

Nephrotic Syndrome ◽

Familial Mediterranean Fever ◽

Periodic Fever ◽

Rapid Progression ◽

Secondary Amyloidosis ◽

Aa Amyloidosis ◽

Glomerular Diseases ◽

Amyloid A ◽

Serum Amyloid A Protein ◽

Mediterranean Fever

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis.

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Long-term efficacy and safety of canakinumab in patients with colchicine-resistant familial Mediterranean fever: results from the randomised phase III CLUSTER trial

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-217419 ◽

2020 ◽

Vol 79 (10) ◽

pp. 1362-1369 ◽

Cited By ~ 2

Author(s):

Seza Ozen ◽

Eldad Ben-Cherit ◽

Ivan Foeldvari ◽

Gil Amarilyo ◽

Huri Ozdogan ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Disease Activity ◽

Phase Iii ◽

Physician Global Assessment ◽

Efficacy And Safety ◽

Open Label ◽

Amyloid A ◽

Term Efficacy ◽

Mediterranean Fever

ObjectivesTo evaluate the long-term efficacy and safety of canakinumab to treat patients with colchicine-resistant familial Mediterranean fever (crFMF) during Epoch 4 (weeks 41 to 113) of the CLUSTER study.MethodsPatients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks during a 72-week period. We evaluated disease activity every 8 weeks using the physician global assessment (PGA) of disease activity, counting the number of flares, and measuring concentrations of C reactive protein (CRP) and serum amyloid A (SAA). Safety was studied by determination and classification of observed adverse events (AEs). We analysed safety and efficacy separately in two subgroups of patients receiving a cumulative dose of less than 2700 mg, or equal or more than 2700 mg.ResultsOf the 61 patients that started the CLUSTER study, 60 entered Epoch 4 and 57 completed it. During the 72-week period, 35/60 (58.3%) patients experienced no flares, and 23/60 (38.3%) had one flare, as compared with a median of 17.5 flares per year reported at baseline. PGA scores indicated no disease activity for the majority of patients throughout the study. Median CRP concentrations were always lower than 10 mg/L, while median SAA concentrations remained over the limit of normal (10 mg/L) but under the 30 mg/L threshold. No new or unexpected AEs were reported.ConclusioncrFMF patients treated with canakinumab during 72 weeks experienced a minimal incidence of flares and good control of clinical disease activity, with no new safety concerns reported.

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Thyroid disorders in familial Mediterranean fever: think about AA amyloidosis!

Clinical Rheumatology ◽

10.1007/s10067-021-05852-y ◽

2021 ◽

Author(s):

Hélène Vergneault ◽

Rim Bourguiba ◽

Samuel Ardois ◽

Anael Dumont ◽

Léa Savey ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Thyroid Disorders ◽

Aa Amyloidosis ◽

Mediterranean Fever

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AB0968 Adrenomedullin Levels in Patients with Familial Mediterranean Fever: A Long Term Follow-Up

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-eular.6129 ◽

2015 ◽

Vol 74 (Suppl 2) ◽

pp. 1222.2-1222

Author(s):

A. Polat ◽

C. Saglam ◽

Y.G. Kurt ◽

G. Basbozkurt ◽

B. Sozeri ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Long Term Follow Up ◽

Mediterranean Fever

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P075 Contribution of biothérapy in pediatric rheumatology: tolérance and efficacy

Rheumatology ◽

10.1093/rheumatology/keab722.067 ◽

2021 ◽

Vol 60 (Supplement_5) ◽

Author(s):

W Messadi ◽

A Salmi ◽

N Cherif

Keyword(s):

Familial Mediterranean Fever ◽

Pediatric Rheumatology ◽

University Hospital ◽

Response To Treatment ◽

Inflammatory Rheumatic Diseases ◽

Good Tolerance ◽

Mediterranean Fever ◽

Mean Time ◽

Hepatic Cytolysis

Abstract Background Biotherapy result of spectacular advances in genetics and research in molecular and cellular biology, has considerably improved the management of rheumatic and autoinflammatory diseases in children. The Objective is to assess the efficacy and tolerance of biotherapy in pediatrics Methods A retro-prospective study was carried out in the Pediatric Department B at the pediatric rheumatology consultation, university hospital center. An operating sheet was drawn up including epidemiological, clinical, paraclinical and therapeutic data of the cases diagnosed as well as their evolution on biotherapy. Results 26 children received treatment with biotherapy. 73% presented with JIA (54% systemic, 19% polyarticular with positive RF, 19% severe uveitis, and 4% familial Mediterranean fever. 4% behçet disease The mean time to start biotherapy was 12 months [2–48]. There is a clear clinical and biological improvement for 93% of patients. Etanercept was effective in polyarticular-progressive JIA, Adalimumab in oligoarthritis with severe uveitis, Tocilizumab in systemic forms of JIA and Anakinra in familial Mediterranean fever resistant to colchicine and systemic arthritis. The adverse reactions noted were: one case of tuberculosis, hepatic cytolysis in 4 cases, and one case of psoriasis. Conclusion The introduction of biotherapy in pediatric has considerably improved the management of inflammatory rheumatic diseases and transformed the prognosis of these chronic diseases. The maintenance of the good response to treatment and the good tolerance of biotherapy must be evaluated prospectively over the long term.

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