Tocilizumab for the Treatment of Mevalonate Kinase Deficiency

Rafiq, Nadia; Lachmann, Helen; Joensen, Fróði; Herlin, Troels; Brogan, Paul A.

doi:10.1155/2018/3514645

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…The effectiveness of etanercept varies among studies, leading to a beneficial response in approximately of 60% of reported patients (14,19). Evidence for the effectiveness of anti-IL-6 therapy in MKD is mainly derived from a few case studies in which tocilizumab, a monoclonal antibody against the IL-6 receptor, resulted in the remission of inflammatory episodes in MKD patients (98)(99)(100)(101). Another study reported four patients, who discontinued tocilizumab treatment because of lack of efficiency (102).…”

Section: Treatment Options For Mkdmentioning

confidence: 99%

Compromised Protein Prenylation as Pathogenic Mechanism in Mevalonate Kinase Deficiency

Politiek

Waterham

2021

Front. Immunol.

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Mevalonate kinase deficiency (MKD) is an autoinflammatory metabolic disorder characterized by life-long recurring episodes of fever and inflammation, often without clear cause. MKD is caused by bi-allelic pathogenic variants in the MVK gene, resulting in a decreased activity of the encoded enzyme mevalonate kinase (MK). MK is an essential enzyme in the isoprenoid biosynthesis pathway, which generates both non-sterol and sterol isoprenoids. The inflammatory symptoms of patients with MKD point to a major role for isoprenoids in the regulation of the innate immune system. In particular a temporary shortage of the non-sterol isoprenoid geranylgeranyl pyrophosphate (GGPP) is increasingly linked with inflammation in MKD. The shortage of GGPP compromises protein prenylation, which is thought to be one of the main causes leading to the inflammatory episodes in MKD. In this review, we discuss current views and the state of knowledge of the pathogenetic mechanisms in MKD, with particular focus on the role of compromised protein prenylation.

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Section: Treatment Options For Mkdmentioning

confidence: 99%

Compromised Protein Prenylation as Pathogenic Mechanism in Mevalonate Kinase Deficiency

Politiek

Waterham

2021

Front. Immunol.

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“…Literature reviews were performed using "PubMed" and "Web of Science" by searching for the terms "Mevalonate kinase de ciency" and "TNF receptor-associated periodic syndrome" and "tocilizumab". We summarized previously reported cases of tocilizumab treating MKD and TRAPS patients, which showed in Table 2 [15][16][17][18][19][20][21][22] and Table 3 [23][24][25][26]. In previous studies, a total of 11 MKD patients and 4 TRAPS patients were treated with tocilizumab.…”

Section: Literature Reviewmentioning

confidence: 99%

Tocilizumab for the Treatment of Mevalonate Kinase Deficiency and TNF Receptor-Associated Periodic Syndrome: cases report and literature review

Li,

2023

Preprint

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Background Mevalonate kinase deficiency (MKD) and TNF receptor-associated periodic syndrome (TRAPS) are systemic autoinflammatory diseases (SAIDs), which are rare diseases with early-onset, severe condition and difficult diagnosis and treatment. Although different SAIDs have standard treatments, some SAIDs are poorly controlled after routine treatment, which seriously affects the growth and development of children and their quality of life. The purpose of our study is to provide more treatment strategies for SAIDs.Cases presentation: We presented 2 Chinese patients with MKD and TRAPS who were resistant to TNF-α blockade. The patients with MKD and TRAPS still have periodic fever and rash after using etanercept, baricitinib and glucocorticoid. IL-1 antagonists are not available in Chinese Mainland, then they commenced intravenous tocilizumab (240mg every 3 weeks). After they were treated by one or two doses of tocilizumab, they were not suffered from fever and rash so far. Before treatment of tocilizumab in MKD patient, WBC and TNF-α were normal, ESR and CRP increased significantly, and IL-6 increased slightly. After treatment of tocilizumab, ESR and CRP fell to normal, however, IL-6 increased occasionally. In TRAPS patient, ESR, CRP, WBC, IL-6 and TNF-α were increased significantly. After treatment of tocilizumab, ESR, CRP, WBC, IL-6 and TNF-α fell to normal. Two patients were treated with tocilizumab for more than 6 months, and they achieved in clinical and serological remission. Two patients had no adverse reactions after injection of tocilizumab.Conclusions Without IL-1 antagonists in Chinese Mainland, tocilizumab is useful as an alternative drug to the treatment of SAIDs who are resistant to TNF-α blockade.

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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).…”

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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Tocilizumab for the Treatment of Mevalonate Kinase Deficiency

Cited by 6 publications

References 21 publications

Compromised Protein Prenylation as Pathogenic Mechanism in Mevalonate Kinase Deficiency

Compromised Protein Prenylation as Pathogenic Mechanism in Mevalonate Kinase Deficiency

Tocilizumab for the Treatment of Mevalonate Kinase Deficiency and TNF Receptor-Associated Periodic Syndrome: cases report and literature review

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

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