Epidemiology of inclusion body myositis in the Netherlands: A nationwide study

Badrising, Umesh A.; Maat-Schieman, M. L. C.; Duinen, Sjoerd G. van; Breedveld, Ferdinand C.; Doorn, P. van; Engelen, B.G.M. van; Hoogen, Frank van den; Hoogendijk, Jessica E.; Höweler, C. J.; Jäger, Andrea; Jennekens, F. G. I.; Koehler, Peter J.; Leeuw, H. van der; Visser, Marjolein; Verschuuren, Jan J.; Wintzen, Axel R.

doi:10.1212/wnl.55.9.1385

Cited by 181 publications

(133 citation statements)

References 7 publications

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“…11 Patients had to be able to walk at least 3 m without assistance from another person, although use of assistive devices was allowed, and able to ingest adequate intake of energy and protein, defined as at least 20 kcal/ kg/d and 0.6 g protein/kg/d measured by a Food Frequency Questionnaire. 12 Standard protocol approvals, registrations, and patient consents.…”

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confidence: 99%

Treatment of sporadic inclusion body myositis with bimagrumab

et al. 2014

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Objective: To study activin signaling and its blockade in sporadic inclusion body myositis (sIBM) through translational studies and a randomized controlled trial. Methods:We measured transforming growth factor b signaling by SMAD2/3 phosphorylation in muscle biopsies of 50 patients with neuromuscular disease (17 with sIBM). We tested inhibition of activin receptors IIA and IIB (ActRII) in 14 patients with sIBM using one dose of bimagrumab (n 5 11) or placebo (n 5 3). The primary outcome was the change in right thigh muscle volume by MRI at 8 weeks. Lean body mass, strength, and function were secondary outcomes. Twelve of the patients (10 bimagrumab, 2 placebo) participated in a subsequent 16-week observation phase.Results: Muscle SMAD2/3 phosphorylation was higher in sIBM than in other muscle diseases studied (p 5 0.003). Eight weeks after dosing, the bimagrumab-treated patients increased thigh muscle volume (right leg 16.5% compared with placebo, p 5 0.024; left leg 17.6%, p 5 0.009) and lean body mass (15.7% compared with placebo, p 5 0.014). Subsequently, bimagrumabtreated patients had improved 6-minute walking distance, which peaked at 16 weeks (114.6%, p 5 0.008) compared with placebo. There were no serious adverse events; the main adverse events with bimagrumab were mild acne and transient involuntary muscle contractions.Conclusions: Transforming growth factor b superfamily signaling, at least through ActRII, is implicated in the pathophysiology of sIBM. Inhibition of ActRII increased muscle mass and function in this pilot trial, offering a potential novel treatment of sIBM. Classification of evidence:This study provides Class I evidence that for patients with inclusion body myositis, bimagrumab increases thigh muscle volume at 8 weeks. Neurology ® 2014;83:2239-2246 GLOSSARY ActRII 5 activin receptors IIA and IIB; DXA 5 dual-energy x-ray absorptiometry; LBM 5 lean body mass; pSMAD2/3 5 phosphorylated SMAD2/3; QMT 5 quantitative muscle testing; sIBM 5 sporadic inclusion body myositis; 6MWD 5 6-minute walking distance; TGFb 5 transforming growth factor b; TMV 5 thigh muscle volume.Sporadic inclusion body myositis (sIBM) is a slowly progressive degenerative and inflammatory skeletal muscle disease beginning in middle or later life.1 Its clinical features include a specific pattern of muscle involvement (preferential weakness of finger flexors and knee extensors) accompanied by progressive muscle atrophy, distinctive microscopic pathology including endomysial inflammation and rimmed vacuoles, and a recently identified serum autoantibody (against cytosolic 59-nucleotidase 1A) biomarker.2-4 Despite a prominent adaptive immune response characterized by antigen-stimulated B-and T-cell maturation and prominent infiltration into muscle of immune system cells, sIBM is highly refractory to immunosuppressive therapies studied to date. 2Members of the transforming growth factor b (TGFb) superfamily of ligands signal through a heterodimeric receptor system.5 They first bind a type II receptor, such as the TGFb...

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confidence: 99%

Treatment of sporadic inclusion body myositis with bimagrumab

et al. 2014

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“…Research diagnostic categories for IBM are important in the reporting of research on cohorts of patients with IBM and are essential for the conduct of IBM clinical therapeutic trials. Formal research diagnostic criteria and categories for IBM have been proposed since 1987 by individual authors [1][2][3][4] and through publications of consensus expert opinions developed in 5 meetings in 1995, 5 1996, 6,7 2008, 8 2009, 9 and 2011. 10 These publications have created features (e.g., "presence of quadriceps weakness"), categories (Boolean algebraic combinations of features; e.g., definite), and schemes (combinations of categories; e.g., definite, probable, and possible).…”

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confidence: 99%

“…We found that 12 categories could be applied to patients (table), while 12 other categories were not further studied for the following reasons. Two European Neuromuscular Centre (ENMC 1997 probable and ENMC 1997 definite) categories 6 were subsequently replaced with revised versions in the year 2000 7 ; only the revised categories were analyzed here. Four categories lacked specificity for IBM and were not further analyzed: 3 1987 definite, probable, and possible 1 categories lack a requirement for the microscopic detection of inflammatory cells in muscle biopsy specimens, allowing patients with genetic disorders with rimmed vacuoles to be categorized as IBM; and a 1991 criteria set 2 indicated that filamentous inclusions were pathognomonic of IBM, although these were known to be present in a number of hereditary distal myopathies.…”

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confidence: 99%

Evaluation and construction of diagnostic criteria for inclusion body myositis

et al. 2014

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Objective: To use patient data to evaluate and construct diagnostic criteria for inclusion body myositis (IBM), a progressive disease of skeletal muscle. Methods:The literature was reviewed to identify all previously proposed IBM diagnostic criteria.These criteria were applied through medical records review to 200 patients diagnosed as having IBM and 171 patients diagnosed as having a muscle disease other than IBM by neuromuscular specialists at 2 institutions, and to a validating set of 66 additional patients with IBM from 2 other institutions. Machine learning techniques were used for unbiased construction of diagnostic criteria.Results: Twenty-four previously proposed IBM diagnostic categories were identified. Twelve categories all performed with high ($97%) specificity but varied substantially in their sensitivities (11%-84%). The best performing category was European Neuromuscular Centre 2013 probable (sensitivity of 84%). Specialized pathologic features and newly introduced strength criteria (comparative knee extension/hip flexion strength) performed poorly. Unbiased data-directed analysis of 20 features in 371 patients resulted in construction of higher-performing data-derived diagnostic criteria (90% sensitivity and 96% specificity).Conclusions: Published expert consensus-derived IBM diagnostic categories have uniformly high specificity but wide-ranging sensitivities. High-performing IBM diagnostic category criteria can be developed directly from principled unbiased analysis of patient data. Classification of evidence:This study provides Class II evidence that published expert consensusderived IBM diagnostic categories accurately distinguish IBM from other muscle disease with high specificity but wide-ranging sensitivities.

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“…IBM affects males more frequently (3:1), shows an overall prevalence of approximately 4‐15/1000000 (35‐71/1000000 > age 50, respectively), is noticably frequent in Western Australia, Japan, Norway, Olmsted County (Minnesota, USA), and is especially rare in Turkey and India 3, 24, 25, 26, 27, 28, 29, 30, 31. In Japan, the number of diagnosed IBM cases has steadily increased since 1991, whereas the number of PM cases has remained constant 32.…”

Section: Epidemiologymentioning

confidence: 99%

Immune and myodegenerative pathomechanisms in inclusion body myositis

Keller

Schmidt

Lünemann

2017

Ann Clin Transl Neurol

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Inclusion Body Myositis (IBM) is a relatively common acquired inflammatory myopathy in patients above 50 years of age. Pathological hallmarks of IBM are intramyofiber protein inclusions and endomysial inflammation, indicating that both myodegenerative and inflammatory mechanisms contribute to its pathogenesis. Impaired protein degradation by the autophagic machinery, which regulates innate and adaptive immune responses, in skeletal muscle fibers has recently been identified as a potential key pathomechanism in IBM. Immunotherapies, which are successfully used for treating other inflammatory myopathies lack efficacy in IBM and so far no effective treatment is available. Thus, a better understanding of the mechanistic pathways underlying progressive muscle weakness and atrophy in IBM is crucial in identifying novel promising targets for therapeutic intervention. Here, we discuss recent insights into the pathomechanistic network of mutually dependent inflammatory and degenerative events during IBM.

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Epidemiology of inclusion body myositis in the Netherlands: A nationwide study

Cited by 181 publications

References 7 publications

Treatment of sporadic inclusion body myositis with bimagrumab

Treatment of sporadic inclusion body myositis with bimagrumab

Evaluation and construction of diagnostic criteria for inclusion body myositis

Immune and myodegenerative pathomechanisms in inclusion body myositis

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