63hand radiographic scores to predict mortality in RA [ 14 , 19 , 22 , 23 ]. Figures 3.2
and 3.3 Poor RA status according to a joint examination, laboratory measures, and
patient questionnaire measures is more likely to be identifi ed according to low
education level than high age or long duration of disease [ 24 , 25 ]. Low socioeco-
nomic status is associated with a higher likelihood of premature mortality in the
general population, including RA [ 26 ]. Socioeconomic status may be regarded as a
surrogate for the importance of patient actions, in addition to actions of health pro-
fessionals, in the course and outcomes of rheumatic and other chronic diseases.Limitations of Laboratory Test Biomarkers
in Rheumatic Diseases
The discovery in 1948 of rheumatoid factor [ 27 ] and the LE cell [ 28 ] raised hopes
that diagnosis and management of rheumatic diseases could be approached with
“gold standard” biomarkers, analogous to blood pressure in hypertension or serum
glucose in diabetes. Rheumatoid factor and other laboratory discoveries have been
indispensable to understanding of pathogenesis and development of new treatments.
For example, biological therapies, which have added considerably to the capacity to
treat rheumatic diseases, would likely not be available without the discovery of of
rheumatoid factor, leading to subsequent recognition of likely cytokines, immuno-
active cells, and other biomarkers.
In contrast to their immense value for research to understand pathogenesis and
develop new treatments, biomarkers remain of limited value in clinical diagnosis
and management of rheumatic diseases. For example, in RA, rheumatoid factor, anti-
citrullinated protein antibodies (ACPA) , elevated ESR and CRP are found in more
than half of patients with RA at presentation. However, each of these four biomarker
tests is not abnormal in 30–40 % of new patients—a substantial minority.
A meta-analysis of all available studies indicated that rheumatoid factor is found
in only 69 % of patients with RA in 50 studies (similar to the initial 1948 report
[ 27 ]) and ACPA (reported in 1998 [ 29 ]) in only 67 % of patients in 37 studies; fur-
thermore, 5 % of normal individuals have a (false) positive test [ 30 ]. Of course, an
individual who has a positive test for rheumatoid factor or ACPA has a considerably
higher likelihood to have RA compared to individuals in the general population.
However, the prevalence of RA is 0.5 %. In other words, 5 in 1000 people have RA,
while formal studies suggest that 50 among 1000 individuals in the general popula-
tion have a positive rheumatoid factor test [ 30 ]. Therefore, only 1 in 10 with rheu-
matoid factor has RA, and most people in the general population who have a positive
test for rheumatoid factor (or ACPA) do not have RA.
Most people do not have a positive rheumatoid factor test, but the high preva-
lence of musculoskeletal symptoms [ 31 ] leads to many “false-positive” tests. Since
the medical history and physical examination dominate clinical decisions in the
management of RA, (unlike many chronic diseases) [ 2 ], one could argue that the
clinical approach to RA need not include a test for rheumatoid factor or ACPA,
although most rheumatologists would not agree.
3 PROMs (MDHAQ/RAPID3) and Physician RheuMetric Measures