TY - JOUR
T1 - Clinical signs and symptoms in a joint model of four disease activity parameters in juvenile dermatomyositis
T2 - a prospective, longitudinal, multicenter cohort study
AU - van Dijkhuizen, E H Pieter
AU - De Iorio, Maria
AU - Wedderburn, Lucy R
AU - Deakin, Claire T
N1 - Funding Information:
EHPvD received funding from the 7th Framework programme of the EU, SP3-People, support for training and career development for researchers (Marie Curie), Network for Initial Training (ITN), FP7-PEOPLE-2011-ITN, under the Marie Skłodowska-Curie grant agreement No 289903. CTD was supported by a fellowship from The Myositis Association (TMA). Funding for the UK JDM Cohort and Biomarker study has been provided by generous grants from the Wellcome Trust UK (085860), Action Medical Research UK (SP4252), The Myositis Support Group UK, Arthritis Research UK (14518, 20164), The Henry Smith Charity and Great Ormond Street Children’s Charity (V1268), The Myositis Association, The Medical Research Council and the National Institute for Health Research (NIHR) Translational Research Collaboration (TRC) Rare Diseases. This research was supported by the NIHR Great Ormond Street Hospital for Children NHS Foundation Trust Biomedical Research Centre (NIHR-GOSH BRC). The JDM Cohort study is adopted onto the NIHR Comprehensive Research Network. The Arthritis Research UK Centre for Adolescent Rheumatology at UCL, UCL Hospital and GOSH is supported by grants from Arthritis Research UK (20164) and Great Ormond Street Children’s Charity. This is a summary of independent research funded by the NIHR’s Rare Diseases Translational Research Collaboration. The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/8/15
Y1 - 2018/8/15
N2 - BACKGROUND: It is currently impossible to predict the prognosis of patients with juvenile dermatomyositis (JDM). The aim of this study was to find clinical features most strongly associated with outcome variables in JDM as a first step towards tailor-made treatment.METHODS: In a large, prospectively followed, multicenter cohort study of 340 patients with JDM, each contributing multiple visits, a Bayesian model of disease activity was developed, using the four continuous outcome variables creatine kinase (CK), childhood myositis assessment score (CMAS), manual muscle testing of 8 muscle groups (MMT8) and the physician's global assessment of disease activity (PGA). Covariates were clinical signs and symptoms. Correlations among visits of the same patient were resolved by introducing subject-specific random effects.RESULTS: Myalgia and dysphonia were associated with worse disease activity according to all outcome variables. Periorbital rash, rash on the trunk, rash over large joints, nail fold changes and facial swelling were associated with higher PGA. Notably, periorbital rash was also associated with higher CK and lower CMAS and nail fold changes with lower CMAS. Contractures were associated with lower CMAS and MMT8 and higher PGA. Patients with higher CMAS exhibited a higher MMT8 as well. PGA had the highest probability among the four outcome variables of being abnormal even if the other three outcome variables were normal.CONCLUSIONS: The signs and symptoms associated with disease activity could be used to stratify patients and adapt treatment plans to disease activity. The correlation between CMAS and MMT8 and the unique information captured by PGA implied that PGA should be maintained as an outcome variable, whereas CMAS and MMT8 might be simplified.
AB - BACKGROUND: It is currently impossible to predict the prognosis of patients with juvenile dermatomyositis (JDM). The aim of this study was to find clinical features most strongly associated with outcome variables in JDM as a first step towards tailor-made treatment.METHODS: In a large, prospectively followed, multicenter cohort study of 340 patients with JDM, each contributing multiple visits, a Bayesian model of disease activity was developed, using the four continuous outcome variables creatine kinase (CK), childhood myositis assessment score (CMAS), manual muscle testing of 8 muscle groups (MMT8) and the physician's global assessment of disease activity (PGA). Covariates were clinical signs and symptoms. Correlations among visits of the same patient were resolved by introducing subject-specific random effects.RESULTS: Myalgia and dysphonia were associated with worse disease activity according to all outcome variables. Periorbital rash, rash on the trunk, rash over large joints, nail fold changes and facial swelling were associated with higher PGA. Notably, periorbital rash was also associated with higher CK and lower CMAS and nail fold changes with lower CMAS. Contractures were associated with lower CMAS and MMT8 and higher PGA. Patients with higher CMAS exhibited a higher MMT8 as well. PGA had the highest probability among the four outcome variables of being abnormal even if the other three outcome variables were normal.CONCLUSIONS: The signs and symptoms associated with disease activity could be used to stratify patients and adapt treatment plans to disease activity. The correlation between CMAS and MMT8 and the unique information captured by PGA implied that PGA should be maintained as an outcome variable, whereas CMAS and MMT8 might be simplified.
KW - Bayesian model
KW - Clinical associations
KW - Disease activity
KW - Juvenile dermatomyositis
KW - Longitudinal data
UR - http://www.scopus.com/inward/record.url?scp=85052093113&partnerID=8YFLogxK
U2 - 10.1186/s13075-018-1687-8
DO - 10.1186/s13075-018-1687-8
M3 - Article
C2 - 30111380
SN - 1478-6354
VL - 20
SP - 180
JO - Arthritis research & therapy
JF - Arthritis research & therapy
IS - 1
M1 - 180
ER -