Tocilizumab for the Treatment of Mevalonate Kinase Deficiency

Mevalonate kinase deficiency (MKD) is a severe autoinflammatory disease caused by recessive mutations in MVK resulting in reduced function of the enzyme mevalonate kinase, involved in the cholesterol/isoprenoid pathway. MKD presents with periodic episodes of severe systemic inflammation, poor qualit...

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Main Authors: Nadia K. Rafiq, Helen Lachmann, Frodi Joensen, Troels Herlin, Paul A. Brogan
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Case Reports in Pediatrics
Online Access:http://dx.doi.org/10.1155/2018/3514645
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author Nadia K. Rafiq
Helen Lachmann
Frodi Joensen
Troels Herlin
Paul A. Brogan
author_facet Nadia K. Rafiq
Helen Lachmann
Frodi Joensen
Troels Herlin
Paul A. Brogan
author_sort Nadia K. Rafiq
collection DOAJ
description Mevalonate kinase deficiency (MKD) is a severe autoinflammatory disease caused by recessive mutations in MVK resulting in reduced function of the enzyme mevalonate kinase, involved in the cholesterol/isoprenoid pathway. MKD presents with periodic episodes of severe systemic inflammation, poor quality of life, and life-threatening sequelae if inadequately treated. We report the case of a 12-year-old girl with MKD and severe autoinflammation that was resistant to IL-1 and TNF-α blockade. In view of this, she commenced intravenous tocilizumab (8 mg/kg every 2 weeks), a humanised monoclonal antibody targeting the IL-6 receptor (IL-6R) that binds to membrane and soluble IL-6R, inhibiting IL-6-mediated signaling. She reported immediate cessation of fever and marked improvement in her energy levels following the first infusion; after the fifth dose, she was in complete clinical and serological remission, now sustained for 24 months. This is one of the first reported cases of a child with MKD treated successfully with tocilizumab and adds to the very limited experience of this treatment for MKD. IL-6 blockade could therefore be an important addition to the armamentarium for the treatment of this rare monogenic autoinflammatory disease.
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spelling doaj-art-c19e88f1064a44c9983df6ff60ce0fb72025-08-20T03:23:30ZengWileyCase Reports in Pediatrics2090-68032090-68112018-01-01201810.1155/2018/35146453514645Tocilizumab for the Treatment of Mevalonate Kinase DeficiencyNadia K. Rafiq0Helen Lachmann1Frodi Joensen2Troels Herlin3Paul A. Brogan4Infection and Inflammation and Rheumatology Section, University College London Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1 E1H, UKNational Amyloidosis Centre, University College London Division of Medicine, London, UKNational Hospital of the Faroe Islands, J. C. Svabos Gøta, Tórshavn 100, Faroe IslandsDepartment of Paediatrics, Pediatric Rheumatology Clinic, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, DenmarkInfection and Inflammation and Rheumatology Section, University College London Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1 E1H, UKMevalonate kinase deficiency (MKD) is a severe autoinflammatory disease caused by recessive mutations in MVK resulting in reduced function of the enzyme mevalonate kinase, involved in the cholesterol/isoprenoid pathway. MKD presents with periodic episodes of severe systemic inflammation, poor quality of life, and life-threatening sequelae if inadequately treated. We report the case of a 12-year-old girl with MKD and severe autoinflammation that was resistant to IL-1 and TNF-α blockade. In view of this, she commenced intravenous tocilizumab (8 mg/kg every 2 weeks), a humanised monoclonal antibody targeting the IL-6 receptor (IL-6R) that binds to membrane and soluble IL-6R, inhibiting IL-6-mediated signaling. She reported immediate cessation of fever and marked improvement in her energy levels following the first infusion; after the fifth dose, she was in complete clinical and serological remission, now sustained for 24 months. This is one of the first reported cases of a child with MKD treated successfully with tocilizumab and adds to the very limited experience of this treatment for MKD. IL-6 blockade could therefore be an important addition to the armamentarium for the treatment of this rare monogenic autoinflammatory disease.http://dx.doi.org/10.1155/2018/3514645
spellingShingle Nadia K. Rafiq
Helen Lachmann
Frodi Joensen
Troels Herlin
Paul A. Brogan
Tocilizumab for the Treatment of Mevalonate Kinase Deficiency
Case Reports in Pediatrics
title Tocilizumab for the Treatment of Mevalonate Kinase Deficiency
title_full Tocilizumab for the Treatment of Mevalonate Kinase Deficiency
title_fullStr Tocilizumab for the Treatment of Mevalonate Kinase Deficiency
title_full_unstemmed Tocilizumab for the Treatment of Mevalonate Kinase Deficiency
title_short Tocilizumab for the Treatment of Mevalonate Kinase Deficiency
title_sort tocilizumab for the treatment of mevalonate kinase deficiency
url http://dx.doi.org/10.1155/2018/3514645
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AT troelsherlin tocilizumabforthetreatmentofmevalonatekinasedeficiency
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