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AB0687 Non-Invasive Assessment of Muscle Quality by MRI as a Potential Marker of Disease Modification in Bimagrumab-Treated SIBM Patients
  1. D. Laurent1,
  2. B. Tseng2,
  3. S. Greenberg3,
  4. P. Houston4,
  5. D. Papanicolaou5,
  6. R. Roubenoff1
  1. 1Novartis Institutes for Biomedical Research, Basel, Switzerland
  2. 2Novartis Institutes for Biomedical Research, Cambridge
  3. 3Boston Children's Hospital and Brigham and Women's Hospital, Boston, United States
  4. 4Novartis Pharma AG, Basel, Switzerland
  5. 5Novartis Pharmaceuticals Corporation, East Hanover, United States

Abstract

Background Bimagrumab is a monoclonal antibody that inhibits ligand binding to the activin receptor IIA/B thereby stimulating muscle growth. In a proof of concept study, bimagrumab increased thigh muscle volume (TMV) by 6.5% (p=0.024) and decreased intramuscular adipose tissue (IMAT) by 3% (p=n.s.) after 8 weeks of treatment.

Objectives Using qualitative muscle MRI to characterize disease severity and modification in sporadic inclusion body myositis (sIBM) patients treated with bimagrumab.

Methods 14 patients were randomized to single IV dose (30 mg/kg) of bimagrumab (n=11) or placebo (n=3). Disease severity was assessed by visual scoring of PD images. TMV, IMAT, subcutaneous (SC) adipose tissue volume, and individual muscle volume (IMV) were determined from proton-density (PD) MR images using semi-automated segmentation approaches. In addition, the relative fat fraction (%FF) and apparent coefficient of diffusion (ADC) were measured from three-point Dixon and diffusion-weighted images, respectively.

Results After 8 weeks of treatment, mean score for disease activity (21.5±0.6) remained unchanged. Although insignificant, decrease in %FF (−7% vs baseline) was seen at Week-8 in 4 patients while SC and IMAT volumes were slightly reduced. At baseline, fat-infiltrated muscles had lower ADC values than previously reported (1.46±0.11 vs 1.62±0.14 x10-3 mm2/sec) and a trend towards normal values was observed after treatment. At baseline, IMAT content was greater in anterior than in posterior thigh muscles (49% vs 23%, p<0.01). Individual muscle volumes (IMV) increased more in the posterior (+8%) than in anterior thigh compartment (+4%, p<0.01). At Week-16, further decrease in IMAT in all muscles (-7% vs baseline, p<0.05) correlated well with the change from baseline in IMV at Week-8 (r=0.57, p<0.05).

Conclusions MRI may be used in a comprehensive non-invasive way to demonstrate potential of bimagrumab as a disease-modifying therapy which may potentially lead to restoration of normal muscle quality and composition.

References

  1. Amato AA et al. Neurology. 2014;83(24):2239-46.

  2. Qi J et al. J Magn Reson Imaging. 2008;27(1):212-7.

Acknowledgements Study Supported By: Novartis Pharma AG

Disclosure of Interest D. Laurent Shareholder of: Novartis, Employee of: Novartis Institutes for Biomedical Research, Basel, Switzerland, B. Tseng Employee of: Novartis Institutes for Biomedical Research, Cambridge, USA, S. Greenberg Grant/research support from: Novartis Pharma AG, P. Houston Employee of: Novartis Pharma AG, Basel, Switzerland, D. Papanicolaou Employee of: Novartis Pharmaceuticals Corporation, East Hanover, USA, R. Roubenoff Employee of: Novartis Institutes for Biomedical Research, Basel, Switzerland.

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