Good medium-term efficacy of tocilizumab in DMARD and anti-TNF-α therapy resistant reactive amyloidosis

Hakala, M; Immonen, Kai; Korpela, Markku; Vasala, M.; Kauppi, Markku

doi:10.1136/annrheumdis-2012-202156

Cited by 21 publications

(11 citation statements)

References 10 publications

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“…The present patient's eGFR was significantly decreased compared to that of patients in the previously mentioned case reports. Adequate treatment, including TCZ, is essential at an early stage for successful management of renal AA amyloidosis [13]. Second, the renal location of the amyloid deposition might be different in our patient and the previously reported patients.…”

Section: Discussionmentioning

confidence: 67%

Therapeutic Benefits of Tocilizumab Vary in Different Organs of a Patient with AA Amyloidosis

Matsui

Okayama

Tsushima

et al. 2014

Case Reports in Nephrology

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Systemic reactive AA amyloidosis is a life-threatening complication of chronic inflammatory diseases. Anti-interleukin-6 receptor, tocilizumab (TCZ), has been shown to improve clinical symptoms of patients with AA amyloidosis, accompanied with regression of the amyloid deposition. We report a case of AA amyloidosis evaluated by histology of multiple organs before and after TCZ treatment. A woman in her 60s with rheumatoid arthritis was referred to our hospital because of cardiac and renal dysfunction. A gastric and renal biopsy revealed the deposition of AA amyloid, and echocardiography revealed concentric left ventricular hypertrophy. Her estimated glomerular filtration rate was decreased to 8.6 mL/min/1.73 m2, and B-type natriuretic peptide, C-reactive protein, and serum amyloid A protein were significantly elevated. TCZ treatments markedly decreased her serum amyloid A protein and C-reactive protein levels, but hemodialysis was required 1 year later. Endoscopic gastric rebiopsy 3 years after initiation of TCZ treatments revealed the regression of amyloid deposition and echocardiography revealed improvement of her left ventricular hypertrophy. However, a renal rebiopsy revealed that the amyloid deposition had not regressed. In conclusion, these observations suggest that the therapeutic effects of TCZ can vary among organs in patients with AA amyloidosis.

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Section: Discussionmentioning

confidence: 67%

Therapeutic Benefits of Tocilizumab Vary in Different Organs of a Patient with AA Amyloidosis

Matsui

Okayama

Tsushima

et al. 2014

Case Reports in Nephrology

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“…Autoinflammatory diseases such as familial Mediterranean fever, TNF-receptor-associated periodic syndromes, the hyper-IgD syndrome, and cryopyrin-associated periodic syndromes often respond to some of these biologicals, especially to anakinra that is directed against IL-1 [34]. Tocilizumab, an anti-IL-6 receptor antibody, directly suppresses the production of C-reactive protein and SAA by the liver [35]. …”

Section: Treatmentmentioning

confidence: 99%

The Prevalence and Management of Systemic Amyloidosis in Western Countries

Nienhuis

Bijzet

Hazenberg³

2016

Kidney Dis

107

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Background: Amyloidosis has been a mystery for centuries, but research of the last decennia has clarified many of the secrets of this group of diseases. A protein-based classification of amyloidosis helps to understand problems that were part of the obsolete clinical classification in primary, secondary, and familial amyloidosis. All types of amyloid are secondary to some underlying precursor-producing process: each type is caused by a misfolded soluble precursor protein that becomes deposited as insoluble amyloid fibrils. Summary: The incidence of amyloidosis is not well documented, but probably falls between 5 and 13 per million per year. Prevalence data are scarce, but one UK study indicates about 20 per million inhabitants. Amyloidosis can be localized (amyloid deposited in the organ or tissue of precursor production) or systemic (amyloid at one or more sites distant from the site of precursor production). The major systemic types of amyloidosis are AL (associated with a light chain-producing plasma cell dyscrasia), AA (associated with longstanding inflammation), wild-type ATTR (associated with normal transthyretin and old age), and hereditary ATTR (associated with a transthyretin mutation) amyloidosis. Imaging techniques, such as cardiac ultrasound, magnetic resonance imaging, bone scintigraphy, and serum amyloid P component scintigraphy, are useful both for diagnosing amyloidosis and for assessing disease severity. Serologic markers are useful for detecting organ disease and disease monitoring during follow-up. Current treatment modalities are directed against the ongoing supply of precursor proteins and thereby aim to stop further accumulation of amyloid. Novel treatment modalities, such as interference with amyloid formation and even removal of amyloid, are being studied. A well-thought and planned monitoring during follow-up helps to assess the effect of treatment and to early detect possible progression of amyloidosis. Key Messages: Clinical management comprises histologic proof of amyloid, evidence of systemic deposition, reliable typing, precursor assessment, severity of organ disease, risk assessment and prognosis, choice of treatment, and planned monitoring during follow-up. Facts from East and West: (1) AL amyloidosis is the most prevalent type of amyloidosis accounting for 65% of the amyloidosis-diagnosed patients in the UK and for 93% of the amyloidosis-diagnosed patients in China. The predisposition of men over women to develop AL amyloidosis might be higher in China than in Western countries (2:1 vs. 1.3:1). Both in the East and West, incidence increases with age. At the time of diagnosis, edema is twice as frequent and the proportion of renal involvement is higher in Chinese compared to Western patients. (2) Melphalan followed by autologous stem cell transplantation (ASCT) is the current standard therapy but is restricted to eligible patients. The efficacy and safety of bortezomib combined with dexamethasone were proven in Western patients and recently confirmed in a Chinese cohort. Recent stu...

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“…Hakala et al have described fi ve cases of infl ammatory arthritides complicated with AA amyloidosis who failed to respond to anti-TNF agents but improved significantly on TCZ treatment [ 97 ]. Recently, with a reference to Hakala study, two abstracts presented in EULAR 2014 reported their follow-up data on the effi cacy of TCZ in patients with FMF amyloidosis [ 98 , 99 ].…”

Section: Anti-il-6 Treatmentmentioning

confidence: 99%

The Emerging Treatments in Familial Mediterranean Fever

Özdoğan

Uğurlu

2015

Rare Diseases of the Immune System

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9As described in detail by Ben-Chetrit in the previous chapter, colchicine is the mainstay of the treatment of familial Mediterranean fever (FMF) [ 1 , 2 ]. If used daily for lifelong, it controls the febrile attacks in the majority of the patients and prevents the development of amyloidosis, the most serious complication of the disease.Colchicine is very effective as shown in controlled trials [ 3 ] and within the therapeutic range. Side effects are rare and/or mild, so that it can be used even during pregnancy and lactation, plus it is very cheap; however, even colchicine has some limitations in the treatment of FMF:1. Response to therapy: A small proportion of patients with FMF continue to experience attacks despite proper dose and good compliance to colchicine. Overall, it has been accepted that colchicine prevents febrile attacks in more than 60 % of patients and signifi cantly reduces the number of attacks in another 20-30 %. Five to ten percent of patients do not respond to therapy [ 4 , 5 ].Compliance is a main issue among patients who report attacks under colchicine treatment. Approximately 40 % of the patients are not compliant and receive lower than the dose needed to control the infl ammatory attacks and thus prone to high risk of amyloidosis [ 6 ]. Therefore, it is very important to check the compliance and the daily dose before diagnosing the patient as unresponsive to colchicine therapy. Recently the data that comes from the Eurofever Registry which collects information on patients with various autoinfl ammatory diseases, including FMF, showed that among the 121 FMF patients on colchicine, 62 % reported complete, 36 % partial, and 2 % no response [ 7 ]. In another recent report, only 5 % of the compliant patients on proper dose of colchicine continued to experience frequent attacks [ 8 ].

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Good medium-term efficacy of tocilizumab in DMARD and anti-TNF-α therapy resistant reactive amyloidosis

Cited by 21 publications

References 10 publications

Therapeutic Benefits of Tocilizumab Vary in Different Organs of a Patient with AA Amyloidosis

Therapeutic Benefits of Tocilizumab Vary in Different Organs of a Patient with AA Amyloidosis

The Prevalence and Management of Systemic Amyloidosis in Western Countries

The Emerging Treatments in Familial Mediterranean Fever

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