[Thesis]. Manchester, UK: The University of Manchester; 2015.
Aim: The aim of this thesis was to validate the 2010 American College of Rheumatology/European
League Against Rheumatism classification criteria for rheumatoid arthritis (RA), in
particular with respect to its construct validity and the role of autoantibodies within
the criteria.Methods: This thesis used data from the Norfolk Arthritis Register, a
longitudinal inception cohort of adults (16 years and over) with inflammatory polyarthritis
(IP), defined as at least 2 swollen joint for at least 4 weeks. The 2010 criteria
were used to define RA, firstly in a re-estimation of the incidence rates (IR) with
comparisons made to incidence defined by the previous criteria set; and secondly in
a study comparing mortality rates in patients with RA to those of the general population,
and how these rates changed over time. Analyses were performed testing the ability
of the 2010 criteria to identify those patients with IP at increased risk of mortality,
disability, disease severity and radiographic damage. The levels and number of autoantibodies
present were investigated as predictors of mortality in patients with IP. The association
between anti-carbamylated protein (anti-CarP) antibodies and long term disease outcomes
were investigated.Results: The incidence of RA was 40 per 100 000 population; baseline
IRs were similar to the cumulative IRs using the previous criteria set over 5 years.
Patients who were seronegative were less likely to be classified as RA by the 2010
criteria. Mortality rates in patients with RA were higher compared to the general
population (standardised mortality ratio 1.16, 95 percent confidence interval (CI)
1.04-1.29) and declined over the study period at the same rate as the general population.
Patients with IP who fulfilled the 2010 criteria had increased risk of early death
(hazard ratio (HR) 1.35, 95 percent CI 1.13-1.64), as well as increased levels of
disability (beta 0.38, 95 percent CI 0.33-0.43), disease severity (beta 1.63, 95 percent
CI 1.54-1.73) and radiographic damage (beta 0.33, 95 percent CI 0.20-0.47) throughout
follow up. Patients with two autoantibodies had an increased risk of early death
(HR 1.35, 95 percent CI 1.09-1.68), but there was no association with early death
and the levels of these antibodies. Anti-CarP antibody positivity was independently
associated with worse disability (beta 0.12, 95 percent CI 0.02-0.21) and disease
severity (beta 0.23, 95 percent CI 0.07-0.39) throughout follow up.Conclusions: The
2010 ACR/EULAR classification criteria for RA identify patients with IP early in their
disease course and recognise those at increased risk of mortality and poor outcomes.
The 2010 criteria may miss a subgroup of seronegative patients who nevertheless have
a poor prognosis. Novel autoantibodies may be useful to identify this subgroup.