Evidence Based Recommendatinos for Diagnosis and Management of Mevalonate Kinase Deficiency (MKD)

Nienke ter Haar¹, Jerold Jeyaratnam², Jordi Anton³, Caroline Galeotti⁴, Karyl Barron⁵, Paul Brogan⁶, Luca Cantarini⁷, Marco Gattorno⁸, Gilles Grateau⁹, Veronique Hentgen¹⁰, Michael Hofer¹¹, Tilmann Kallinich¹², Isabelle Kone-Paut¹³, Jasmin Kuemmerle-Deschner¹⁴, Helen Lachmann¹⁵, Huri Ozdogan¹⁶, Seza Ozen¹⁷, Ricardo Russo¹⁸, Yosef Uziel¹⁹, Carine Wouters²⁰, Brian Feldman²¹, Bas Vastert², Nico Wulffraat²², Anna Simon²³ and Joost Frenkel², ¹Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands, ²University Medical Center Utrecht, Utrecht, Netherlands, ³Pediatric Rheumatology Unit. Hospital Sant Joan de Déu. Universitat de Barcelona, Barcelona, Spain, ⁴Bicêtre Hospital, University of Paris SUD, Paris, France, ⁵NIH, Bethesda, MD, ⁶Rheumatology Unit, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom, ⁷University of Siena, Siena, Italy, ⁸Istituto Giannina Gaslini, Genova, Italy, ⁹Service De Médecine Interne, Hopital Tenon, Paris, France, ¹⁰Versailles Hospital, Le Chesnay Cedex, France, ¹¹Centre Multisite Romand de Rhumatologie Pediatrique, Lausanne, Switzerland, ¹²Charite, University Medicine Berlin, Berlin, Germany, ¹³Department of Pediatric Rheumatology, Reference Centre for Autoinflammatory Disorders CEREMAI, Bicêtre Hospital, University of Paris SUD, Paris, France, ¹⁴Pediatrics, University Hospital Tuebingen, Tuebingen, Germany, ¹⁵UK National Amyloidosis Centre, University College London Medical School, London, United Kingdom, ¹⁶Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey, ¹⁷Deptartment. of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey, ¹⁸Immunology & Rheumatology, Hospital De Pediatria, Buenos Aires, Argentina, ¹⁹Tel-Aviv University, Sackler School of Medicine, Tel-Aviv, Israel, ²⁰University of Leuven, Laboratory of Pediatric Immunology, University Hospital Leuven, Leuven, Belgium, ²¹Rheumatology, The Hospital for Sick Children, Toronto, ON, Canada, ²²Pediatric rheumatology, Wilhelmina Children's Hospital/ UMC Utrecht, Utrecht, Netherlands, ²³Radboudumc, Nijmegen, Netherlands

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: diagnosis, evidence-based practice, fever and treatment

Session Information

Title: Pediatric Rheumatology - Clinical and Therapeutic Aspects: Systemic Juvenile Idiopathic Arthritis, Spondyloarthropathy and Miscellaneous Pediatric Rheumatic Diseases

Session Type: Abstract Submissions (ACR)

Background/Purpose Mevalonate kinase deficiency (MKD) is a rare hereditary autoinflammatory syndrome that can lead to significant morbidity. Evidence-based guidelines are lacking and management is mostly based on physician’s experience. Consequently, treatment regimens differ throughout Europe. In 2012, a European initiative called SHARE (Single Hub and Access point for pediatric Rheumatology in Europe) was launched to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. One of the aims of SHARE was to provide evidence based recommendations for diagnosis and treatment of MKD.

Methods Evidence based recommendations were developed using the European League Against Rheumatism (EULAR) standard operating procedure. An expert committee was instituted, consisting of pediatric and adult rheumatologists. The expert committee defined search terms for the systematic literature review. Two independent experts scored articles for validity and level of evidence. Recommendations derived from the literature were evaluated by an online survey. Those with less than 80% agreement on the online survey or with relevant comments of the experts were reformulated. Subsequently, all recommendations were discussed at a consensus meeting using the nominal group technique. Recommendations were accepted if more than 80% agreement was reached.

Results The literature search yielded 618 articles, of which 28 were considered relevant and therefore scored for validity and level of evidence. Fourteen were scored valid and used in the formulation of the recommendations. Sixteen recommendations were suggested in the online survey and discussed during the consensus meeting. Six general recommendations on management, three recommendations for diagnosis, six for monitoring and seven for treatment were accepted with more than 80% agreement. Topics covered are following:

general recommendations: the use of the multidisciplinary team, treatment goals, and vaccinations
diagnosis: diagnostic value of Gaslini diagnostic score, IgD and urinary mevalonic acid excretion
monitoring: the use of AIDAI in clinical studies, monitor frequency, minimal assessments in all MKD and additional assessments in severe MKD patients, risk of infection and macrophage activation syndrome
treatment: NSAIDs, glucocorticoids, IL-1 blockade, etanercept, switching biologicals, colchicine, statins and hematopoietic stem cell transplantation

Conclusion The SHARE initiative provides recommendations for diagnosis and treatment for MKD and thereby facilitates improvement and uniformity of care throughout Europe.

Disclosure:

N. ter Haar,
None;

J. Jeyaratnam,
None;

J. Anton,
None;

C. Galeotti,

Novartis Pharmaceutical Corporation,

K. Barron,
None;

P. Brogan,

Novartis, Roche,

Novartis Pharmaceutical Corporation,

L. Cantarini,

Novartis Pharma AG, SOBI,

M. Gattorno,
None;

G. Grateau,
None;

V. Hentgen,

Novartis Pharmaceutical Corporation,

Novartis, Pfizer, Roche,

M. Hofer,
None;

T. Kallinich,

Novartis, SOBI,

Novartis Pharmaceutical Corporation,

I. Kone-Paut,
None;

J. Kuemmerle-Deschner,

Novartis Pharmaceutical Corporation,

SOBI,

H. Lachmann,
None;

H. Ozdogan,
None;

S. Ozen,
None;

R. Russo,
None;

Y. Uziel,

Novartis Pharmaceutical Corporation,

Abbvie, Neopharm, Novartis, Roche,

C. Wouters,
None;

B. Feldman,
None;

B. Vastert,
None;

N. Wulffraat,
None;

A. Simon,

Servier,

Novartis, SOBI, Xoma,

J. Frenkel,

European Union ERANET,

Novartis Pharmaceutical Corporation,

SOBI,

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