Elsevier

Neuromuscular Disorders

Volume 23, Issue 12, December 2013, Pages 1044-1055
Neuromuscular Disorders

Workshop report
188th ENMC International Workshop: Inclusion Body Myositis, 2–4 December 2011, Naarden, The Netherlands

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Introduction

The 188th ENMC workshop titled “Inclusion Body Myositis” was held in Naarden, The Netherlands, 2–4 December 2011. The workshop received supplementary funding from the Myositis Support Group UK. This workshop aimed to build on the work of two previous IBM workshops held in the MRC Centre London 2008 and Paris 2009 [1], [2]. Its aims were to (1) review the diagnostic criteria for IBM, (2) foster future collaborative working in immunological and genetic IBM research, (3) review natural history studies and clinical trial protocols, (4) review the current status of clinical trials outcome measures and map the processes required to improve these, (5) establish the requirements for a global IBM registry, and (6) to scope the work required for the establishment of standards of care for IBM.

The workshop was attended by 24 representatives from UK, France, Germany, Belgium, Netherlands, Sweden, Denmark, Australia and USA. Participants included neurologists, rheumatologists, physiotherapists, industry representatives and patient representatives.

Section snippets

Diagnostic criteria

David Hilton-Jones led review and discussion of the diagnostic criteria for IBM. As we do not know the cause or primary pathogenic mechanisms of IBM there is no “gold standard” for diagnosis. The original IBM diagnostic criteria proposed by Griggs et al. [3] were primarily a pathological definition. Indeed in the Griggs’ criteria “definite IBM” was defined on histological features with no reference to the clinical features. When all of the major pathological features (partial invasion,

Immunological studies

Olivier Benveniste reviewed the evidence of amyloid and phosphorylated tau deposits in certain muscle fibres of IBM patients and the arguments for protein degradation dysfunctions (at both, proteasome and autophagy levels). From different experiments in mouse models, it appears that the forced over-expression of different kind of proteins, not only amyloids (APP42, gelsolin) but also MHC class I in muscle, leads to muscle weakness, appearance of vacuoles with, in parallel, increase of

Genetic studies

Merrilee Needham reviewed the genetic studies in IBM. Until recently, genetic studies in IBM have been limited to candidate gene studies due to the low incidence of IBM, (with estimates ranging from 1 per million to 14 per million) [14], [15]. Using this approach, the immune features of IBM have prompted studies of the Major Histocompatibility Complex (MHC). These have discovered a susceptibility region in the 8.1 ancestral haplotype in a 172 Kb region near the HLA-DRB1⁎0301 (HLA-DR3) allele.

Registries

Maggie Walter led a discussion on patient registries. These have been already proven to be useful tools to overcome fragmentation and to facilitate research in disease epidemiology, genotype-phenotype correlation, and natural history studies. They are also valuable for monitoring standards of care and greatly facilitate feasibility studies for clinical trials and recruitment into clinical trials. Currently there are European and global effort to set up patient registries for Duchenne Muscular

Natural history

Natural history studies are important in helping with clinical trials planning and the selection of the best measures of disease progression of IBM. Michael Hanna and James Miller presented data from their on-going prospective observational natural history studies in IBM. At the time of this workshop Michael Hanna’s group had enrolled 51 participants and there was one year follow up data on 21 subjects. Entry criteria included Griggs criteria or MRC 2008 criteria [2], [32]. Although there have

Clinical trial protocols and outcome measures

Anthony Amato, Linda Lowes, Michael Rose and Farah Seedat discussed protocols used for clinical trials in IBM and studies on the performance of outcome measures used in IBM studies. The outcome measures used in IBM were collated from the few published randomized, blinded, placebo-controlled trials in IBM [47] and from a pre workshop survey of all the participants (Table 2).

Pathology measures included muscle biopsy analysis of inflammation and attempted estimation of the levels of accumulated

Standards of care

Discussion on standards of care was led by Thomas Sejersen. The relative rarity of IBM outside of specialist muscle clinics and the variation of practice even amongst IBM experts means that care standards differ not only between individual countries but also within them. This situation weakens the call for adequate healthcare resources for those with IBM. Variations in clinical outcomes that arise from variable standards of care are also likely to compromise the valid measurement of treatment

Future projects

Rasch analysis of IBMFRS.

Rasch analysis of MMT data in IBM.

Workshop on IBM registries.

Project grant for setting Standards of Care for IBM.

Conclusion

The workshop set out to review and scope the work done and required for clinical trials readiness in IBM. The proposed new diagnostic criteria should enlarge the potential pool of IBM recruits and allow recruitment of cases at a stage when treatment might be more effective. There is a need for harmonisation of IBM registries as an aid to IBM recruitment as well as helping in the selection of outcome measures and identification of sub-groups of those with IBM that may more treatment responsive.

List of participants

  • Anthony A. Amato; Harvard Medical School, Boston, Massachusetts, USA.

  • Baziel van Engelen; Nijmegen Neuromuscular Centre, The Netherlands.

  • Brian Tseng; Novartis Pharmaceuticals Corporation, New Jersey, USA.

  • Christina Buccirechtweg; Novartis Pharmaceuticals Corporation, New Jersey, USA.

  • David Hilton Jones; John Radcliffe Hospital, Oxford, UK.

  • Farah Seedat; Kings College Hospital, London, UK.

  • Ingrid E. Lundberg; Karolinska University Hospital, Sweden.

  • James Miller Royal Victoria Infirmary, Newcastle Upon

Acknowledgements

This workshop was made possible by the financial support of the European Neuromuscular Centre (ENMC) and its main sponsors: Muskelsvindfonden (Denmark), Association Française contre les Myopathies (France), Deutsche Gesellschaft für Muskelkranke (Germany), Telethon Foundation (Italy), Drustvo Distrofikov Slovenije (Slovenia), Schweizerische Stiftung für die Erforschung der Muskelkrankheiten (Switzerland), Prinses Beatrix Fonds (The Netherlands), Vereniging Spierziekten Nederland (The

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    Members of the ENMC IBM Working Group are listed at the end of this report.

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