Failure of tocilizumab treatment in a CINCA patient: clinical and pathogenic implications

Snegireva, Ludmila; Kostik, Mikhail M.; Caroli, Francesco; Ceccherini, Isabella; Gattorno, Marco; Chasnyk, Vyacheslav

doi:10.1093/rheumatology/ket121

Cited by 9 publications

(8 citation statements)

References 10 publications

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“…Cryopyrinopathies include a recently identified group of hereditary diseases characterized by recurrent febrile episodes associated with multisystem inflammatory symptoms. The inheritance pattern is autosomal dominant, or a de novo mutation traced to a missense mutation on chromosome 1q44 (3). The protein isolated from the genetic mutations is called cryopyrin, which regulates of inflammation and apoptosis (4) mediating its effects by forming an inflammasome which causes caspase-1 mediated activation of IL-1 (2).…”

Section: Discussionmentioning

confidence: 99%

“…Resolution of ocular findings has been reported with use of anakinra. Tocilizumab, a humanized monoclonal antibody against Il-6 has been tried (2); however, mixed results have been reported with its use (3). The ultimate goal of these therapeutic interventions is to avoid chronic inflammation and end organ damage by amyloidosis.…”

Section: Discussionmentioning

confidence: 99%

“…Ophthalmic manifestations in CAPS are rare, but optic neuropathies have been sparsely reported (1,5). Ocular affections include corneal topographic abnormalities, posterior stromal opacities, corneal leukomas, band shaped keratopathy, recurrent conjunctivitis, anterior and panuveitis, iris synechiae, cataracts, optic nerve pallor, and epiretinal membrane (1,3). Although the most severe manifestations are reported in CINCA (5), milder phenotypes occur in MWS and FCAS (3).…”

Section: Discussionmentioning

confidence: 99%

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Cryopyrin-Associated Periodic Syndrome in Neuro-Ophthalmology

Bindiganavile¹,

Beres²,

Bhat³

et al. 2020

Journal of Neuro-Ophthalmology

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C ryopyrin-associated periodic syndromes (CAPS) are a set of rare inflammatory conditions related to disorders of the protein, cryopyrin. CAPS manifests as recurrent coldinduced urticaria, fever, hearing loss, and meningitis which vary by severity: a milder form (familial cold autoinflammatory syndrome [FCAS]); an intermediate form (Muckle-Wells syndrome [MWS]); and a more severe form (chronic infantile neurological cutaneous and articular syndrome [CINCA]), previously called neonatal-onset multisystem inflammatory disease (1,2). We describe 2 cases of CAPS presenting with neuro-ophthalmic findings including optic neuropathy. To the best of our knowledge, these are the first such cases in the English language neuro-ophthalmic literature.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Cryopyrin-Associated Periodic Syndrome in Neuro-Ophthalmology

Bindiganavile¹,

Beres²,

Bhat³

et al. 2020

Journal of Neuro-Ophthalmology

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“…Tocilizumab has been successfully used in three patients with TRAPS (129)(130)(131) and in seven HIDS/MKD cases (132)(133)(134)(135)(136) in whom anti-TNF and/or anti-IL-1 agents had previously failed. Negative results have been reported in two CAPS (CINCA/NOMID) patients treated with tocilizumab (119,137). No evidence on the use of tocilizumab in PFAPA syndrome is currently reported.…”

Section: Other Autoinflammatory Diseasesmentioning

confidence: 99%

Current Therapeutic Options for the Main Monogenic Autoinflammatory Diseases and PFAPA Syndrome: Evidence-Based Approach and Proposal of a Practical Guide

Soriano

Espinosa

et al. 2020

Front. Immunol.

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recommendation based on the EULAR standardized operating procedures for EULAR-endorsed recommendations (11, 12). Category Evidence from LEVELS OF EVIDENCE 1A Meta-analysis of randomized controlled trials 1B At least one randomized controlled trial 2A At least one controlled study without randomization 2B At least one type of quasi-experimental study 3 Descriptive studies, such as comparative studies, correlation studies, or case-control studies 4 Expert committee reports or opinions and/or clinical experience of respected authorities Grade Directly based on STRENGTH OF RECOMMENDATION A Category 1 evidence B Category 2 evidence or extrapolated recommendation from category 2 evidence C Category 3 evidence or extrapolated recommendation from category 1 or 2 evidence D Category 4 evidence or extrapolated recommendation from category 2 or 3 evidence the number of attacks (20). Since then, colchicine has become the basis of FMF treatment, and later on, several clinical trials definitively established its efficacy in preventing attacks and developing amyloidosis (21-23). Colchicine was officially approved in 2009 by the US Food and Drug Administration (FDA) for the acute flares of gout and FMF, as a single-ingredient oral formulation (Colcrys R) (24). Nowadays, according to 2016 EULAR recommendations for the management of FMF, colchicine represents the first-line treatment in FMF, with a level of evidence 1B and grade of recommendation A (13). Among other biological functions, colchicine has antiinflammatory properties based on the inhibition of leukocyte chemotaxis, which is caused by its interaction with tubulin and the resulting dysfunction of microtubules. Microtubules, composed by α-and β-tubulin heterodimers, are involved in cell division, signal transduction, migration, secretion, and regulation of gene expression (25). Colchicine has the ability to bind in a poorly reversible manner to soluble non-polymerized tubulin in the cells, with the formation of a tubulin-colchicine complex (26, 27), and the subsequent movement inhibition of intracellular granules (28). The predominant effect of colchicine on leukocytes, and more specific on granulocytes, has been correlated with the high concentrations of the drug in neutrophils compared to lymphocytes and monocytes. In this regard, defects in the efflux pumps with low activity of the P-glycoprotein 1 (PGY-1) efflux pump of granulocytes might explain the accumulation of colchicine in their cytoplasm (29, 30). Other anti-inflammatory effects of colchicine include the reduction of TNF-α production by macrophages and TNF-α

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“… 6 reported that tocilizumab was not effective in such patients because CAPS is an IL-1mediated disease with a marginal increase in the levels of circulating IL-6. 7 Therefore, we request the authors further data to carefully demonstrate the effect of tocilizumab in CAPS.…”

mentioning

confidence: 99%