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Original research
Longitudinal observational study investigating outcome measures for clinical trials in inclusion body myositis
  1. Gina Sangha1,
  2. Bohao Yao2,
  3. Daniel Lunn2,
  4. Iwona Skorupinska3,
  5. Louise Germain3,
  6. Damian Kozyra4,
  7. Matt Parton3,
  8. James Miller5,
  9. Michael G Hanna3,4,
  10. David Hilton-Jones1,
  11. Jane Freebody1,
  12. Pedro M Machado3,4,6
  1. 1 Department of Neurology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  2. 2 Department of Statistics, University of Oxford, Oxford, UK
  3. 3 Queen Square Centre for Neuromuscular Diseases, University College Hospitals NHS Foundation Trust, London, UK
  4. 4 Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, UK
  5. 5 Department of Neurology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  6. 6 Centre for Rheumatology, Division of Medicine, University College London, London, UK
  1. Correspondence to Dr Pedro M Machado, Neuromuscular Diseases, University College London, London WC1B 5EH, UK; p.machado{at}ucl.ac.uk

Abstract

Objective To describe decline in muscle strength and physical function in patients with sporadic inclusion body myositis (IBM).

Methods Manual muscle testing (MMT), quantitative muscle testing (QMT) and disability scoring using the IBM Functional Rating Scale (IBMFRS) were undertaken for 181 patients for up to 7.3 years. The relationship between MMT, QMT and IBMFRS composite scores and time from onset were examined using linear mixed effects models adjusted for gender and age of disease onset. Adaptive LASSO regression analysis was used to identify muscle groups that best predicted the time elapsed from onset. Cox proportional hazards regression was used to evaluate time to use of a mobility aid.

Results Multilevel modelling of change in percentage MMT, QMT and IBMFRS score over time yielded an average decline of 3.7% (95% CI 3.1% to 4.3%), 3.8% (95% CI 2.7% to 4.9%) and 6.3% (95% CI 5.5% to 7.2%) per year, respectively. The decline, however, was not linear, with steeper decline in the initial years. Older age of onset was associated with a more rapid IBMFRS decline (p=0.007), but did not influence the rate of MMT/QMT decline. Combination of selected muscle groups allowed for generation of single measures of patient progress (MMT and QMT factors). Median (IQR) time to using a mobility aid was 5.4 (3.6–9.2) years, significantly affected by greater age of onset (HR 1.06, 95% CI 1.04 to 1.09, p<0.001).

Conclusion This prospective observational study represents the largest IBM cohort to date. Measures of patient progress evaluated in this study accurately predict disease progression in a reliable and useful way to be used in trial design.

Data availability statement

Data are available on reasonable request. All analyses are described in the manuscript. For additional information, please contact the corresponding author.

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Data availability statement

Data are available on reasonable request. All analyses are described in the manuscript. For additional information, please contact the corresponding author.

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Footnotes

  • GS and BY are joint first authors.

  • Twitter @pedrommcmachado

  • Contributors All authors critically revised the manuscript for important intellectual content. Specific roles included study design (GS, DH-J and PMM), data collection (IS, LG, DK, MP, JM, MGH, DH-J, JF and PMM), statistical analyses (GS, BY and DL) and drafting of the first version of the manuscript (GS, DH-J and PMM).

  • Funding Study supported by grants from the National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration (BRC148/NS/MH) and Myositis UK (grant reference not available). PMM is supported by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre (BRC).

  • Disclaimer The views expressed are those of the authors and not necessarily those of the (UK) National Health Service (NHS), the NIHR, or the (UK) Department of Health.

  • Competing interests PMM has received grants and/or honoraria from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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