PM Machado 1 P Houston 2 C Sinclair 1 J Thornton 1 T Yousry 1 A Genge 3 I Scholten 2 L Lowes 4 D Laurent 5 DA Papanicolaou ID: 830250
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Slide1
Baseline characteristics of a prospective natural history study of sporadic inclusion body myositis including MRI assessment
P.M. Machado1, P. Houston2, C. Sinclair1, J. Thornton1, T. Yousry1, A. Genge3, I. Scholten2, L. Lowes4, D. Laurent5, D.A. Papanicolaou6, M.G. Hanna1
Muscle Study Group Scientific Annual MeetingSeptember 24-26, 2016 at Snowbird, UT
1
Medical Research Council Centre for Neuromuscular Diseases, University College London Institute of Neurology, London, UK;
2
Novartis Pharma AG, Basel, Switzerland;
3
Montreal Neurological Institute and Hospital, Montreal, QC, Canada;
4
Nationwide Children’s Hospital, Columbus, OH, USA;
5
Novartis
Institutes for Biomedical Research, Basel, Switzerland
;
6
Novartis Pharmaceuticals Corporation, East Hanover, NJ,
USA
Slide2Disclosures
Pedro M. Machado and Michael G. Hanna serve as consultants to Novartis and declare research support from MRC Centre grant award.Linda Lowes serves as a consultant to PTC, Sarepta, and Bristol Meyer Squib. There was no payment from Novartis for participation in this study. Her institution has received grant support for clinical trials from Novartis. John Thornton received research support from MRC Centre grant award. Parul Houston, Ingo Scholten, Didier Laurent, and Dimitris A. Papanicolaou are employees of Novartis and may be eligible for Novartis stock and stock options. Angela Genge was employed with Novartis from January 2014 to July 2014.The data has been
previously presented as a poster at the 2nd Congress of European Academy of Neurology; May 28–31, 2016, Copenhagen, Denmark.2
Slide3Introduction
Sporadic inclusion body myositis (sIBM) is a rare, debilitating degenerative and inflammatory disorder associated with aging.Characterized by progressive weakness and atrophy of proximal and distal muscles.1,2,3There are limited data that longitudinally characterize the functional impairment, patient burden and economic impact of sIBM.The sIBM Physical Functioning Assessment (sIFA) is a newly developed patient-reported outcome that measures physical function. 11 questions that assess the impact of sIBM on upper and lower extremity function as well as dysphagia.431. Cortese A. et al
. Neuromuscul Disord. 2013;23:404-12; 2.Cox FM, et al. Brain. 2011;134:3167–75; 3. Benveniste O, et al. Brain. 2011;134:3176–84; 4. Williams V, et al. Muscle Nerve. 2016 [Epub ahead of print].
Slide4Objectives
To characterize the clinical progression and functional impact of sIBM over time, as measured by sIFA.To assess thigh muscle composition using MRI.4MRI, magnetic resonance imaging; sIBM, sporadic inclusion body myositis; sIFA, sIBM Physical Functioning Assessment
Slide5Study design and participants
This is a longitudinal, natural history study in patients with sIBM across sites in Canada, Sweden, UK and the US.As of November 30, 2015 (data cut-off date), a total of 184 patients had been recruited. Inclusion criteriapatients aged ≥45 years. diagnosis of sIBM.1,2 patients willing and able to complete the patient questionnaires and the functional assessments. Patients with concurrent diagnosis of any other neurologic or neuromuscular disease that affected the same muscle groups as sIBM were not included in the study.51. Hilton-Jones D,
et al. Neuromuscul Disord. 2010;20:142–7; 2. Rose MR, ENMC IBM Working Group. Neuromuscul Disord. 2013; 23:1044–55.sIBM, sporadic inclusion body myositis
Slide6Assessments
The following data were collected at baselinesIFA total score.Quadriceps quantitative muscle testing (QMT).Hand-grip dynamometry.6-minute walking distance (6MWD).Physician assessment of disease severity.Thigh Muscle Volume (TMV) and the corresponding Inter/Intramuscular Adipose Tissue (IMAT) volume was assessed by MRI in a subset of 19 patients.PD- and T1-weighted images, 1.5T Siemens Avanto6sIFA
, sIBM Physical Functioning Assessment
Slide7Statistical analysis
Correlations were made between the sIFA patient-reported outcome and assessments of mobility/strength (6MWD and quadriceps QMT) in a subset of 137 patients. Correlations between sIFA and objective assessments of muscle composition measured using MRI were analyzed in a subset of 19 patients.A non-parametric Spearman correlation coefficient was calculated for the correlation analyses.76MWD, 6-minute walking distance; sIFA, sIBM physical f
unctioning assessment; QMT, quadriceps quantitative muscle testing
Slide8Demographics and baseline characteristics of the study population
EthnicityCaucasian, n (%)Asian, n (%)Other, n (%)Black, n (%)176 (96.2)3 (1.6)3 (1.6)1 (0.5)Gender, male, n (%)132 (72.1)Age (years), mean (SD)
68.2 (7.9)Time since symptom onset to baseline visit (years), mean (SD)a9.8 (5.7)Time since symptom onset to diagnosis (years), mean (SD)b4.8 (4.6)Ambulatory patients, n (%)172 (94.0)Prior medication prescribed for sIBM, n (%)13 (7.1)Any comorbid conditions, n (%)142 (77.2)Number of comorbid conditions, mean (SD)5.5 (4.0)
Enrolled population, N=184;
cut-off date: November 30, 2015
a
Enrollment
year minus year of first symptoms;
b
Year
of diagnosis minus year of first symptoms
Ambulatory was defined as patients who are not wheelchair bound and the 6-MWD was at least 1 meter (intermittent use of wheelchair or scooter is allowed. However, the patient must not be aided by a person when performing the walk test but may use a gait aid device)
8
6-MWD, 6-minute walking distance; n,
number of patients in population; SD, standard deviation; sIBM, sporadic inclusion body myositis
Slide9Disease characteristics
Patients with falls in the month prior to enrollment, n (%)62 (33.9)Fall consequences in the 12 months prior to enrollmentHospitalization, n (%)Fractures, n (%)Healthcare visits, n (%)5 (2.7)10 (5.5)
43 (23.5)Walking aidsInside or around the home, n (%)Outside the home, n (%)70 (38.3)117 (63.9)6-MWD (m), mean (SD)a324.7 (139.9)sIFA total score, mean (SD)b46.2 (23.3)Disease severity assessed by physician
Mild
, n (%)
Moderate
, n (%)
Severe
, n (%)
Very severe
, n (%)
65 (35.5)
88 (48.1)
27 (14.8)
3 (1.6)
a
Data
available for 172 of 184 enrolled patients.
b
Normalized
score ranged from 0 (no difficulty) to 100 (highest difficulty).
Cut-off date: November 30, 2015
9
6-MWD, 6-minute walking distance; n,
number of patients in population; SD, standard deviation; sIBM, sporadic inclusion body myositis
Slide10Results
10
Association between sIFA total score and physician assessment of severity.Data available for 137 of 184 enrolled patients; Cut-off date: July 31, 2015.sIBM, sporadic inclusion body myositis; sIFA, sIBM physical functioning assessment
0
20
40
60
80
100
Physician rating of
sIBM
symptoms
sIFA
total score
Severe
Moderate
Mild
No difficulty
Highest difficulty
Countries
UK
US
Canada
Sweden
Slide11Results
11
Correlation between sIFA total score and 6-MWD.
R=-0.79
0
20
40
60
80
100
Total distance walked (m)
sIFA
total score
0
100
200
300
400
500
600
700
No difficulty
Highest difficulty
R=Spearman correlation
coefficient
Countries
UK
US
Canada
Sweden
Data
available for
137
of 184 enrolled
patients; Cut-off
date: July 31, 2015
.
6-MWD, 6-minute walking distance;
sIFA
, sIBM physical functioning assessment
Slide12Results
12
Correlation between sIFA total score and QMT quadriceps.
No difficulty
Highest difficulty
R=Spearman correlation
coefficient
Countries
UK
US
Canada
Sweden
Data
available for
137
of 184 enrolled
patients; Cut-off
date: July 31, 2015
.
6-MWD, 6-minute walking distance;
sIFA
, sIBM physical functioning assessment
R=-0.66
Slide13Results
13
Correlation between MRI relative IMAT and sIFA total score.Note: MRI correlations with sIFA were available from 19 patients; MRI was performed using a 1.5T Siemens Avanto scanner and a proton-density weighted pulse sequence; Cut-off date: July 31, 2015. IMAT, inter/intramuscular adipose tissue; relative IMAT=IMAT volume x 100/(TMV+IMAT+SAT); MRI, magnetic resonance imaging; SAT; subcutaneous adipose tissue; sIFA, sIBM physical functioning assessment
R=0.35
0
20
40
60
80
100
sIFA
total score
Relative IMAT (%)
100
80
60
40
20
0
No difficulty
Highest difficulty
R=Spearman correlation
coefficient
Countries
UK
US
Canada
Sweden
Slide14Results
14
No difficulty
Highest difficulty
R=Spearman correlation
coefficient
Countries
UK
US
Canada
Sweden
R=-0.63
0
20
40
60
80
100
sIFA
total score
Relative TMV (%)
100
80
60
40
20
0
Note: MRI correlations with
sIFA
were available from 19 patients; MRI was performed using a 1.5T Siemens
Avanto
scanner and a proton-density weighted pulse sequence;
Cut-off date: July 31, 2015.
IMAT, inter/intramuscular adipose tissue; MRI, magnetic resonance imaging
; SAT,
subcutaneous adipose tissue
;
sIFA
, sIBM physical functioning assessment; TMV, thigh muscle volume; relative TMV=TMV x 100/(TMV+IMAT+SAT)
Correlation between MRI relative
TMV
and
sIFA
total score
.
Slide15Conclusions
Significant functional impairment in patients with sIBM was observed in this study.This study demonstrated significant correlations of sIFA with clinical outcomes as well as objective assessments of muscle composition as assessed by MRI.This study provided data about the validity of MRI muscle composition as an outcome measure in sIBM. Findings from this study will help to determine clinical progression, functional impact, and the disease burden of sIBM over time. 15MRI, magnetic resonance imaging; sIFA, sIBM physical functioning assessment; sIBM, sporadic inclusion body myositis
Slide16Acknowledgements
Authors sincerely thank the principal investigators and support staff at the all centers of this study, and the patients enrolled in this study.Authors would also like to acknowledge Preetinder Kaur from Novartis Healthcare Pvt. Ltd. for medical writing support. 16