Workshop reportInternational Workshop on Inclusion Body Myositis held at the Institute of Myology, Paris, on 29 May 2009
Introduction
This 1-day workshop was organized by Olivier Benveniste and David Hilton-Jones and assembled 20 clinicians, pathologists and researchers (see the list of participants) from four countries (UK, USA, Austria, France). This workshop followed one held in London 1 year earlier with some common participants [1] in order to reinforce a collaborative interface between several international groups actively investigating the clinical features, pathogenesis and treatment of sporadic inclusion body myositis (sIBM). To date, all drugs tested in randomized clinical trials (RCT) appear to be comparable to placebo [2], [3], [4], [5], [6], [7], [8], [9]. Nevertheless, new molecules are emerging [10], [11]. The assessment of potential new treatments is hampered by difficulties in the design of trials, relating in part to the slowly progressive nature of the disorder and uncertainties about the natural history, and the low incidence and prevalence of the disease. Evaluation of required sample size for future sIBM trials has been calculated from the results of two studies using two doses (30 and 60 μg/weekly) of βIFN (without any difference in strength between the 57 placebo or IFN treated patients) [2], [3]. For a two-arm, 6-month therapeutic intervention, aiming to show arrest of disease progression, it would require 208 subjects per group [2], [3]. The enrolment of such a number of patients would be achievable only in a collaborative international multicentre study. Treatments that slow, rather than arrest, progression would need larger numbers, and also longer studies with associated increased costs. The first part of the meeting reviewed the currently widely used diagnostic criteria proposed by RC Griggs et al. [12]. The need for consensus with respect to pathological assessment of muscle biopsy specimens, particularly immunohistochemistry, was agreed. The second part of the meeting was devoted to defining the outcome measures for such trials, and finally we explored the possibilities for international RCTs.
Section snippets
Diagnostic criteria of sIBM
Olivier Benveniste presented the preliminary results of a study called “Natural history and history under treatment of sIBM: the Pitié-Salpêtrière/Oxford study”. Patients were included on the basis of typical clinical features at presentation and on long-term review, with pathological features not inconsistent with the diagnosis of sIBM (in other words, the type of patient seen in everyday practice). One hundred and thirty-six patients (57% males) were included. First symptoms started at 61
Measuring outcomes for RCT
The second part of the meeting concerned the clinical and immunological monitoring of sIBM patients for future trials.
Jean-Yves Hogrel presented a pilot study on a subgroup of 22 untreated patients (mean age 70) from the “Oxford/Pitié-Salpêtrière project” evaluating their strength and mobility by different myometric methods (dynamometric measurements for handgrip, wrist, elbow, ankle and knee flexion and extension) and functional scales (6 min walk test with accelerometer, Walton, Karnofsky,
Therapeutic approaches and future trials
Before the final discussion, Marinos Dalakas reviewed current understanding of the immunophysiopathology of the disease and how this might aid the development of novel approaches to treatment [11].
sIBM is clearly a very complex disorder. In addition to T-cell-mediated cytotoxicity identical to that observed in PM, the disease has degenerative features consisting of vacuoles and accumulation of stressor and amyloid-related proteins in muscle fibers not invaded by T cells. This observation
Concluding remarks
Some phase II trials with the use of innovative therapies have been accomplished [10], [11], or are planned, not only in the field of immunosuppressive drugs (campath, anti-CD3, rapamycin), but also with a β2-agonist with anabolic properties (formoterol), with myostatin blocking-antibodies/peptides, and with anti protein aggregation drugs (bapineuzumab, rember). By their concept, these trials need the inclusion of less than 30 patients so can be undertaken by collaboration between one or two
List of participants
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Yves Allenbach, Institut de Myologie, Paris, France
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Valerie Askanas, USC Neuromuscular Center, Los Angeles, USA
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Olivier Benveniste, Institut de Myologie, Paris, France
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Olivier Boyer, Inserm (U905), Rouen, France
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Serge Braun, AFM, Evry, France
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Catherine Champseix, Institut de Myologie, Paris, France
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Marinos Dalakas, Imperial College, London, UK
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Odile Dubourg, Neuropathologie, Paris, France
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Bruno Eymard, Institut de Myologie, Paris, France
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Marguerite Guiguet, Biostatistics INSERM U720, Paris, France
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Mike
Acknowledgements
This workshop was sponsored by the Association Française contre les Myopathies. We thank Catherine Champseix for helping to organise this meeting.
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2015, Neuromuscular DisordersCitation Excerpt :The inflammation found in muscle biopsies of these patients was undistinguishable from that found in PM [4,5]. Gradually, clinical differences between IBM and PM became more important [1,8–10] and some patients diagnosed with PM turned out to have IBM at follow up [11–15] raising doubt about the validity of endomysial localization of inflammation with invasion of non-necrotic fibers as a diagnostic criterion for PM [10,16,17]. We investigated the disease course in patients with endomysial mononuclear cell infiltrates with invasion of non-necrotic fibers, hypothesizing that their disease course is in keeping with IBM and not PM, even if they did not fulfill histopathological or clinical criteria for IBM at onset.