Outcome measures and clinical trial readiness in Idiopathic Inflammatory Myopathies (IIM)

Number 213
Date 18 September 2015

Location: Heemskerk, The Netherlands.

This workshop was sponsored by ENMC members, ATyr pharma, LFB Biopharmaceuticals, MedImmune/AstraZeneca, The Myositis Association USA and Myositis Group UK.


Organizers: Prof. Olivier Benveniste (France) and Dr. Lisa Rider (USA).

A multidisciplinary group of 22 participants from 8 different countries took part in this workshop, including clinical and basic researchers and 3 patient representatives.

The participants of the 213th ENMC workshop

Background and aim of the workshop: 

Idiopathic Inflammatory Myopathies (IIM) are classified as polymyositis (PM), overlap myositis (OM), dermatomyositis (DM), immune mediated necrotizing myopathy (IMNM) and sporadic inclusion body myositis (sIBM). These are all rare diseases. The follow up of these patients is shared between rheumatologists, neurologists, dermatologists, internists and paediatricians from various hospitals in different countries and as a result disease evaluation and treatments may vary.

The former IIM classification is based on clinical and pathological criteria (e.g. muscle biopsies), but lately different myositis specific (or associated) auto-antibodies are increasingly being used as a diagnostic tool. Different auto-antibodies are associated with different health problems, for example: anti-MDA5 antibodies are frequently associated with interstitial lung disease and skin ulcers.

This is an important step forward, because it is a relatively less invasive and expensive way to distinguish IIM from other myopathies.

Regarding treatment, outcome measures (measuring the effects of treatment on a patient) are important in clinical care as well as in measuring the responses to treatments as part of therapeutic trials of new medications. These may be measured in different ways. Objective measures for example are imaging findings or results of a blood test. Subjective outcomes are based on the opinion of the patient, for example questionnaires.

Many initiatives by medical experts on this subject have resulted in a lot of data, but precise longitudinal data, essential for statistical analysis, are lacking.

The aim of this workshop is to find a consensus between rheumatologists and neurologists regarding the evaluation of response to treatment in the different subgroups of IIM.

The workshop attendants: Dr. R. Aggarwal (rheumatologist, USA), Dr. Y. Allenbach (internist, France), Prof. O. Benveniste (internist, France), Prof. J. de Bleecker (neurologist, Belgium), Ms. I. de Groot (Member of the Myositis Workgroup of Spierziekten Nederland, myositis patient, The Netherlands), Dr. H. Devilliers (internist, France), Dr. D. Hilton-Jones (neurologist, UK), Dr. J-Y. Hogrel (bio-engineer, France), Prof. I. Lundberg (rheumatologist, Sweden), Dr. A. Mammen (neurologist, USA), Mr and Mrs. Oakley (Myositis Support group UK), Dr. C. Oddis (rheumatologist, USA), Prof. G. Padberg (research director ENMC), Mr. D. Ponce (AFMTELETHON, manager of Group of Interest Inflammatory Myositis & myositis patient, France), Dr. L. Rider (pediatric rheumatologist, USA), Dr. M. Rose (neurologist, UK), Dr. H. Sanner (pediatric rheumatologist, Norway), Dr. A. Selva O Callaghan (internist, Spain), Prof. M. de Visser (neurologist, The Netherlands), Prof. A. Wells (pulmonologist, UK) and Dr. V. Werth (dermatologist, USA).

On Day 1 the group focused on the different phenotypes of IIM, inclusion criteria for Polymyositis, Dermatomyositis and IMNM and outcome measures on muscle weakness. Presentations from different specialists about the importance of the muscle biopsy, myositis auto-antibodies and ways to test muscle strength  led to discussions about the best way to classify the different IIM:  is that done based on clinical features, pathological findings and/or auto-antibodies?

Mr and Mrs Oakley, founders of Myositis UK told us the results of an inquiry among British myositis patients regarding outcome assessment: questions like what are outcome measures, why and for whom are these important (for doctors or for patients?). The patients agree that the information gathered by tests and questionnaires is important, but that it is also important for doctors to focus on symptoms which reflect patients’ needs and problems, e.g. fatigue. Ms De Groot, a Dutch dermatomyositis patient told her story of her daily life with the illness and the way it affects social life, work etc. Mr. Ponce, a French myositis patient and manager of a Myositis Group of AFMTelethon, contributed to discussions and pointed out the importance of making assessments feasible and relevant for patients.

A full report is published in Neuromuscular Disorders

On Day 2 the discussion continued. We spoke about functional disability, the Myositis Damage Assessment Tool and the Myositis Activity Assessment Tool and evaluations in neuromuscular disorders during clinical trials. Mr. Hogrel from France told us about the possibilities of mechanical innovation. The invention of the Biogrip, a wrist worn accelerometer, seems a promising way to monitor daily activity of IIM patients.

After lunch we talked about the most fatal complication in Myositis, Interstitial Lung Disease, and the challenge of how to determine if breathing muscles are involved and the lungs are affected or responding to treatment. We ended the day talking about  cutaneous features in both adult and juvenile DM and ways to assess these.

On the morning of Day 3 D. Ponce presented Quality of Life (QOL) survey results of the French Myositis interest group, then we focussed on QOL and the usefulness of the many tools (questionnaires) for measuring QOL. For example: skin (related) problems have a huge physical and emotional impact on DM patients, but these are not considered in the various questionnaires. It is stated that physical health and environment are the most highly affected domains in myositis, but patients score lower on all domains regarding Quality of Life compared with healthy volunteers.

Conclusion: after a summary of all the topics which were addressed this weekend, the organizers Dr. L. Rider and Prof. O. Benveniste proposed a new study to re-examine the Core Set Outcome Measures and to develop new measures:

  • MMT (manual muscle testing) 4 or 8,
  • the use of accelerometry (and other mobile Health Apps),
  • QMT (quantitative muscle testing),
  • Physical disability, including observational functional tools such as the Myositis Functional Index, the 6 minute walking test and TUG (timed up and go) and,
  • QoL (Quality of Life) questionnaires.

100 patients in the subgroups DM, PM, IMNM and ASS (anti-synthestase syndrome) are needed and will be seen twice at the appointed hospitals: once at the start of the illness or at the onset of a disease flare and once after 6 months.

An unanimous decision to accept this proposal ended this workshop.

Prof. I. Lundberg proposed to use the Myonet database for this new study. She also invited the attendants to participate in Omeract's MAP (Myositis Activity Profile) study. Prof. Lundberg emphasized the importance to get as many patients (representatives) involved as possible. Participants from France, UK and The Netherlands accepted her invitation.

October 2015, Ingrid de Groot (The Netherlands)

A full report is published in Neuromuscular Disorders (pdf)