Discontinuation of treatment amyloidosis

OBJECTIVES: Anakinra is proven to be effective in controlled trials in terms of attack frequency and subclinical inflammation in colchicine-resistant patients. The objective of this study was to review the patients followed in our single centre with FMF who received anakinra because of insufficient colchicine response. METHODS: The study was conducted at a tertiary rheumatology centre experienced in autoinflammatory diseases. The patients were treated for at least 1 month with anakinra...

INTRODUCTION: Patients with AL amyloidosis and immunoglobulin deposition diseases (IDD) are vulnerable during the COVID-19 pandemic due to the immune compromise from the plasma cell disorder and therapy related immune defects. We describe a local experience in providing care for patients with AL amyloidosis and IDD. METHOD: Patient treatment and disease status since the beginning of the pandemic on March 11, 2020 as declared by WHO, were collected and analyzed. RESULTS: Ninety-six patients with AL amyloidosis and IDD were included...

A 65-year-old woman was hospitalized for heart failure and pneumonia in a nearby hospital. She had been previously diagnosed as light chain (AL) amyloidosis and treated with melphalan plus dexamethasone (Mel-Dex), and lenalidomide plus dexamethasone (Len-Dex). She started treatment including antimicrobials and diuretics, but her renal function worsened progressively, and she was transferred to our hospital for nephrological care. She was treated with antimicrobials, noradrenaline, dobutamine, and continuous hemodiafiltration...

We have previously demonstrated hippocampal hyperglutamatergic signaling occurs prior to plaque accumulation in AβPP/PS1 mice. Here, we evaluate 2-Amino-6-(trifluoromethoxy) benzothiazole (riluzole) as an early intervention strategy for AD, aimed at restoring glutamate neurotransmission prior to substantial Aβ plaque accumulation and cognitive decline. Male AβPP/PS1 mice, a model of progressive cerebral amyloidosis, were treated with riluzole from 2-6 months of age. Morris water maze (MWM), in vivo electrochemistry, and immunofluorescence were performed to assess cognition, glutamatergic neurotransmission, and pathology, respectively, at 12 months...

OBJECTIVES: Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab treatment in RRAL in real-world setting. METHODS: retrospective multi-site study of RRAL patients treated with daratumumab alone and in combinations. RESULTS: Forty-nine patients, diagnosed between 1.1.2008 and 1.2.2018 were included; 27% also had multiple myeloma...

BACKGROUND: Patisiran, an RNA interference therapeutic, has demonstrated robust reduction of wild-type and mutant transthyretin protein and was able to improve polyneuropathy and quality of life following 18 months of treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. In this 24-month Phase II open-label extension study, we evaluated the effects of patisiran treatment (0.3 mg/kg intravenously every 3 weeks) on safety, serum transthyretin levels, and clinical parameters...

OBJECTIVE: Patients with hereditary transthyretin (TTR) amyloidosis (hATTR) often experience disease progression after orthotopic liver transplant (POLT) due in part to wild type ATTR amyloid deposition. The management strategy is not defined. We propose that TTR gene silencing with an antisense oligonucleotide or a small interfering ribonucleic acid may be a treatment for these patients. METHODS: We reviewed the charts of hATTR patients POLT treated with a TTR gene silencing agent at 7 different Amyloid Clinics between 2018-2020...

PURPOSE: The Phase 3 ENDEAVOUR study evaluated revusiran, an investigational RNA interference therapeutic targeting hepatic transthyretin (TTR) production, for treating cardiomyopathy caused by hereditary transthyretin-mediated (hATTR) amyloidosis. METHODS: Patients with hATTR amyloidosis with cardiomyopathy were randomized 2:1 to receive subcutaneous daily revusiran 500 mg (n = 140) or placebo (n = 66) for 5 days over a week followed by weekly doses. Co-primary endpoints were 6-min walk test distance and serum TTR reduction...

Inotersen, a 2'-O-methoxyethyl (2'-MOE) phosphorothioate antisense oligonucleotide, reduced disease progression and improved quality of life in patients with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) in the NEURO-TTR and NEURO-TTR open-label extension (OLE) trials. However, 300 mg/week inotersen treatment was associated with platelet count reductions in several patients. Mean platelet counts in patients in the NEURO-TTR-inotersen group remained ≥140 × 109 /L in 50% and ≥100 × 109 /L in 80% of the subjects...

Revusiran is a 1st-generation short interfering RNA targeting transthyretin conjugated to an N -acetylgalactosamine ligand to facilitate delivery to hepatocytes via uptake by the asialoglycoprotein receptors. Revusiran, in development for the treatment of hereditary transthyretin-mediated amyloidosis, was discontinued after an imbalance in deaths in the "ENDEAVOUR" phase 3 clinical trial. Nonclinical safety assessments included safety pharmacology, acute and repeat-dose toxicity, genotoxicity, and carcinogenicity...

Bortezomib and dexamethasone with cyclophosphamide (CyBorD) or melphalan (BMDex) are commonly used primary treatments for light-chain (AL) amyloidosis, but limited data exist on bortezomib with immunomodulatory drug combinations. We report our experience with primary therapy with a bortezomib, lenalidomide, and dexamethasone (VRD) "light" regimen in 34 consecutive patients with AL amyloidosis. The majority (79%) had cardiac involvement, 15% and 23% were Mayo stage 3A and 3B, respectively, and 54% had renal involvement...

PURPOSE: Neurogenic orthostatic hypotension is a prominent and disabling manifestation of autonomic dysfunction in patients with hereditary transthyretin (TTR) amyloidosis affecting an estimated 40-60% of patients, and reducing their quality of life. We reviewed the epidemiology and pathophysiology of neurogenic orthostatic hypotension in patients with hereditary TTR amyloidosis, summarize non-pharmacologic and pharmacological treatment strategies and discuss the impact of novel disease-modifying treatments such as transthyretin stabilizers (diflunisal, tafamidis) and RNA interference agents (patisiran, inotersen)...

BACKGROUND: Up to 5% of familial Mediterranean fever (FMF) cases are unresponsive to colchicine, through resistance, side effects and toxicity. Anakinra is an alternative treatment for FMF patients whose disease remains uncontrolled with colchicine. We aimed to evaluate anti-interleukin-1 treatment regarding clinical findings, laboratory parameters and quality of life (QoL) among FMF patients presenting resistance and toxicity towards colchicine. DESIGN AND SETTING: Descriptive observational study at the rheumatology clinic, Adnan Menderes University Medical School, Aydın, Turkey...

This prospective, multicenter, phase II study investigated the use of four cycles of bortezomib-dexamethasone induction treatment, followed by high-dose melphalan and autologous stem cell transplantation (SCT) in patients with newly diagnosed light chain amyloidosis. The aim of the study was to improve the hematologic complete remission (CR) rate 6 months after SCT from 30% to 50%. Fifty patients were enrolled and 72% had two or more organs involved. The overall hematologic response rate after induction treatment was 80% including 20% CR and 38% very good partial remissions (VGPR)...

BACKGROUND: Daratumumab is a CD38 monoclonal antibody approved for treating relapsed/refractory and newly diagnosed multiple myeloma. Preclinical daratumumab studies demonstrated cytotoxic activity and reduced tumor growth in B-cell non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle-cell lymphoma (MCL). PATIENTS AND METHODS: This was a phase 2, open-label, multicenter, 2-stage trial. Patients with relapsed/refractory DLBCL, FL, or MCL with ≥ 50% CD38 expression were eligible for stage 1...

Background: Immunoglobulin light-chain amyloidosis (AL amyloidosis) is a rare and often fatal disease for which there is currently no treatment approved by the US Food and Drug Administration or the European Medicines Agency. Treatment options, which are typically based on therapies for multiple myeloma and are used off-label, are associated with substantial adverse events (AEs). Because the severity of AEs is often determined by clinicians, evaluations of treatment tolerability may not fully consider patients' own experience with treatment...

RATIONALE & OBJECTIVE: The approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding including treatment in the adjuvant setting, the immune related toxicities associated with CPI can limit the efficacy of these agents. The literature on the nephrotoxicity of CPI is limited. Here, we present cases of biopsy proven acute tubulointerstitial nephritis (ATIN) and glomerulonephritis (GN) induced by CPIs and discuss potential mechanisms of these adverse effects...

BACKGROUND: The development of proteinuria and reduced glomerular filtration rate is associated with higher mortality among patients with sickle cell disease (SCD). AA amyloidosis, also associated with increased mortality, in SCD is rare. We present a case of a woman with homozygous sickle cell disease with nephrotic syndrome and antibodies to double stranded DNA without clinical features of systemic lupus erythematosus. Kidney biopsy reveals AA amyloidosis and is the first report of concomitant AA amyloidosis with antibodies to double stranded DNA in SCD...

There is no established treatment protocol for amyloid-A (AA) amyloidosis secondary to Familial Mediterranean Fever (FMF). Recently, we reported the efficacy of tocilizumab in 11 amyloidosis cases associated with FMF. In 2 patients of 11, we discontinued the tocilizumab administeration owing to the normalization of amyloidosis-related symptoms, but proteinuria re-occurred eventually. Fortunately, the patients responded to tocilizumab re-treatment. This led us to conclude that physicians should not stop the treatment, even in patients with normalized proteinuria levels...

OBJECTIVE: We aimed to present our single-center real-life experience of canakinumab use in adult patients with familial Mediterranean fever (FMF). METHODS: Data were derived from the Gazi FMF cohort, which was established in 2010. From that year, all patients with FMF were registered. The impact of FMF on their lives was tracked by either an FMF diary or mobile phone application (FMF-AIDD, free to download in App Store and Google Play). The records of patients who were treated with canakinumab were reviewed...