[Thesis]. Manchester, UK: The University of Manchester; 2018.
Background: Long-term consequences of active disease in juvenile idiopathic arthritis
(JIA) include persistent pain, disability and potential joint replacement surgery.
The aims of treatment are therefore clinically inactive disease (CID) and, ideally,
sustained disease remission. This thesis set out to understand CID and remission in
JIA: how they are defined, how commonly they are achieved, long-term outcomes following
their achievement and whether they are associated with factors early in disease.
Methods: The setting for this thesis was the UK Childhood Arthritis Prospective Study
(CAPS), the largest multicentre, prospective inception cohort of JIA globally. Children
and young people (CYP) were selected for each paper based on their dates of recruitment
and categories of disease. At one year following initial presentation to paediatric
rheumatology, CYP were classified as to whether they had fulfilled published criteria
for CID. Initial analyses explored whether different definitions for CID identified
the same groups of CYP. Outcomes to five years were then compared between those achieving
all, some or none of the criteria for CID using multivariable, multilevel logistic
(absence of limited joints), linear (quality of life) and zero-inflated negative binomial
(functional ability) regression models. Finally, risk factors for remission (CID maintained
over two annual follow-ups) were explored using multivariable logistic regression
models. Throughout, multiple imputation under various assumptions was implemented
for missing data.
Results: The majority of CYP in CAPS were female (65%) and had oligoarthritis (50%).
Median age at initial presentation was eight years (IQR 4, 12). At one year, fewer
than 50% of CYP had achieved CID according to published definitions. There was poor
overlap (44%) between groups of CYP identified by two validated definitions, whose
main difference was the inclusion or exclusion of patient-reported wellbeing. The
odds of no limited joints in the long-term did not differ between CYP fulfilling either
definition of CID. However, CYP who achieved CID on scores which included wellbeing
had superior long-term function (OR for no disability: 2.5, 95% CI 1.8, 3.5) and quality
of life (Î²: 3.9, 95% CI 1.6, 6.2) to those who either did not achieve CID or only
achieved it using inflammatory criteria (i.e. had persistent symptoms despite the
absence of inflammation). Finally, there were few factors at initial presentation
which were associated with remission. However, greater improvements in both physician
and patient-reported variables over the first year following initial presentation
were associated with higher odds of remission in the first three years.
Conclusions: The disease burden in JIA remains high with over 50% of CYP not achieving
CID within the first year of disease. Current definitions of CID available for use
in clinical practice as potential treatment targets do not classify the same groups
of CYP and are associated with different long-term outcomes. Further study is required
to define the best outcome measures for CYP with JIA.