Comparison of weakness progression in inclusion body myositis during treatment with methotrexate or placebo

Badrising, Umesh A.; Maat-Schieman, M. L. C.; Ferrari, Michel D.; Zwinderman, Aeilko H.; Wessels, Judith A.M.; Breedveld, Ferdinand C.; Doorn, Pieter A. van; Engelen, B.G.M. van; Hoogendijk, Jessica E.; Höweler, C. J.; Jager, Aeiko E. de; Jennekens, F. G. I.; Koehler, Peter J.; Visser, Marjolein; Viddeleer, Alain R.; Verschuuren, Jan J.; Wintzen, Axel R.

doi:10.1002/ana.10121

Cited by 111 publications

(59 citation statements)

References 12 publications

(10 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous large studies sCK maximum values varied between 5 and 15 times the upper limit of normal [7,12,15,16,18,20]. It remains plausible that the sCK value represents temporary disease activity [5,11,24].…”

Section: Discussionmentioning

confidence: 92%

Inclusion body myositis

et al. 2005

View full text Add to dashboard Cite

The clinical features of inclusion body myositis (IBM) were of minor importance in the design of consensus diagnostic criteria, mainly because of controversial views on the specificity of signs and symptoms, although some authors reported "typical" signs. To re-assess the clinical spectrum of IBM, a single investigator using a standard protocol studied a cohort of 64 patients cross-sectionally. Symptom onset was before the age of 50 years in 20% of cases. Only a few patients (14 %) started with weakness other than that of quadriceps, finger flexor or pharyngeal muscles. The sequence of power loss was erratic, but onset of symptoms with quadriceps weakness predicted an earlier onset of dysphagia in older patients (> or = 56 years) compared with younger ones (< 56 years) (p = 0.02). Despite widespread weakness patients had favourable scores on three commonly used function scales and they kept their employment. Complete wheel-chair dependency was rare (3 %). A dominant characteristic was the anatomical distribution of afflicted muscles: ventral extremity muscle groups were more affected than dorsal muscle groups and girdle muscles were least affected, the latter preserving postural stability. Ankylosis, especially in extension of the fingers,was frequently present. Together with the sparing of intrinsic hand muscles it was helpful in the preservation of many skillful movements. IBM has a unique distribution of muscle weakness. Ankylotic contractures are common. We feel that their joint impact on daily functioning is characteristic for the disease.

show abstract

Section: Discussionmentioning

confidence: 92%

Inclusion body myositis

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Outcome measures utilized Dalakas et al [67] MMT based on expanded MRC scales (0-10), MVICT, symptom and disability scores, and quantitative swallowing studies Walter et al [68] MMT based on modified MRC, Neuromuscular Symptom Score (NSS), the patient's own assessment of improvement, arm outstretched time, and electromyography Muscle Study Group [50,57] QMT with composite MVICT score (Z-score), average MMT score (expanded 0-5 scale), grip strength (kg), Purdue pegboard, (number of pegs in 30 s), ALSFRS, IBMFRS, SF-36, muscle mass (DEXA), CK Dalakas et al [49] MVICT and MMT using modified Medical Research Council (MRC) scores; muscle biopsies to determine changes in the number of autoinvasive T cells and necrotic muscle fibers Rutkove [69] MVICT, MMT, and functional performance testing (time stair climb, up and go, 2 and 6 MWT) Badrising [70] QMT 4À grade converted to a 3.67 in one study while another converts a 4+ grade to 8 and a 4À as a 6. Even with these various conversions, the numbers so obtained cannot be assumed to be an interval scale.…”

Section: Trialmentioning

confidence: 99%

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

Rose

2013

Neuromuscular Disorders

316

274

View full text Add to dashboard Cite

“…In contrast, all previous sIBM randomized trials have not resulted in statistically significant improvements in their primary outcome measures. 13,[17][18][19][20][21][22] With a single dose of 30 mg/kg, bimagrumab exposure is thought to have been above the therapeutic target of saturating ActRII for approximately 2 months. During this time, muscle mass, measured by MRI of the thigh and by DXA of the whole body, increased substantially from baseline, by approximately 5% more than placebo ( figure 3, A and B).…”

mentioning

confidence: 99%

Treatment of sporadic inclusion body myositis with bimagrumab

et al. 2014

View full text Add to dashboard Cite

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...

show abstract

Comparison of weakness progression in inclusion body myositis during treatment with methotrexate or placebo

Cited by 111 publications

References 12 publications

Inclusion body myositis

Inclusion body myositis

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

Treatment of sporadic inclusion body myositis with bimagrumab

Contact Info

Product

Resources

About