Rheumatology News

9 / 16

‘Hot’ joints may predict RA joint damage
BY NICOLA GARRETT
Frontline Medical News
From Arthritis Care & Research
Recording the temperature of skin over an
inflammed joint may identify rheumatoid
arthritis patients at high risk of joint damage,
an exploratory study suggested.
Dermal joint temperature could become a
screening test to “quickly and accurately” identify
individual RA patients at high risk for radiographic
damage and those who may benefit from biologic
therapy, said Dr Maria Greenwald, a rheumatolo-
gist in group practice in Palm Desert, California,
and her colleagues.
During 2009–2014, the investigators enrolled
seropositive RA patients who were on stable
doses of methotrexate (20–25 mg/wk) for the
past 3 months and did not use biologics or other
disease-modifying antirheumatic drugs. It took
9 months to enrol 104 patients with cool joints
and 42 months to enrol 104 patients with hot
joints, suggesting “that at a single office visit, RA
patients on methotrexate are five times more likely
to have cool joints than hot joints,” the researchers
reported.
The results showed that patients in the hot-
joint cohort had a nearly fourfold higher risk of
x-ray damage at 1-year follow-up, compared with
those with cool joints (change in modified van
der Heijde total Sharp score [mTSS]: 8.7 vs 2.5;
P < 0.001). Patients with hot joints had an average
joint temperature exceeding central forehead body
temperature by 1.1° F, whereas those with cool
joints had an average joint temperature of 4.3° F
below central forehead body temperature.
In the cohort of patients with hot joints, 74%
had clear x-ray evidence of new joint damage
(mTSS of 5 or greater), compared with 7% of
cold-joint cohort patients at 1-year follow-up.
Joint temperature at the hand or wrist predicted
x-ray damage in the next year with 92% sensitivity
and 78% specificity. (Arthritis Care Res 2015 Dec
14. doi: 10.1002/acr.22813).
Patients in the hot-joint cohort were younger,
had more recent onset of RA, and had a signifi-
cantly higher Westergren erythrocyte sedimenta-
tion rate than patients in the cool-joint cohort,
the investigators noted.
They suggested a future study might define a
hot-joint cohort as RA patients with a joint that
measures over a set point such as 36.6˚C. “Such
a cutoff would make assessment very simple and
would maintain the specificity and sensitivity of
the model,” they said.
No conflicts of interest were disclosed.
Greater
myocardial
inflammation
found in RA
patients after
heart attack
BY JEFF EVANS
Frontline Medical News
From the International
Journal of Cardiology
The presence of rheumatoid ar-
thritis in individuals who died
from a myocardial infarction
was associated with greater inflam-
matory burden at different levels
of myocardial tissue than in those
without the disease in a small, retro-
spective, case-control autopsy study.
“These findings support the hy-
pothesis that rheumatoid arthritis
(RA) patients are prone to develop
more vulnerable plaques due to
more inflammation in the coronary
arteries, but also develop increased
intramyocardial inflammation indic-
ative of a higher risk of myocardial
tissue damage post MI. This might
not only explain the higher inci-
dence of cardiovascular events in
this population, but also the higher
fatality rate after myocardial infarc-
tion,” wrote Dr Inge AM van den
Oever of the Amsterdam Rheuma-
tology and Immunology Center and
colleagues (Int J Cardiol 2016 Feb 3.
doi: 10.1016/j.ijcard.2016.02.065).
The investigators took tissue sam-
ples from the infarcted left ventricle
and microscopically determined in-
farct border area of five patients with
RA and MI and five controls with
MI but without RA. They found that
RA patients had a greater burden of
inflammatory cells in the adventitia
of infarct-related epicardial coronary
arteries, the intramyocardial vascula-
ture, and the border area of the in-
farcted heart, compared with controls
matched for age, sex, year of death,
grade of stenosis, and infarct phase.
Specifically, the adventitial layer
of the infarct-related epicardial
coronary artery of RA patients had
significantly more lymphocytes and
mast cells. Intramyocardial arteries
in infarct and infarct border areas
of RA patients, compared with con-
trols, showed significantly greater
staining for advanced glycation end
product N-epsilon-(carboxymethyl)
lysine (CML), which is thought to
reflect oxidative damage to cells, as
well as noninfarcted tissues taken
from the right ventricle.
The researchers included cases
and controls from a postmortem tis-
sue database of subjects who under-
went autopsy within 24 hours after
death at the VU University Medical
Centre, Amsterdam, between Janu-
ary 1990 and December 2010.
The research was partly funded by
a grant from the Dutch Society for
Rheumatology. The authors had no
conflicts of interest to declare.
Potential etanercept response biomarker
identified
BY NICOLA GARRETT
Frontline Medical News
From Arthritis & Rheumatology
Researchers have identified DNA methyla-
tion as a potential biomarker of response to
etanercept in an epigenome-wide association
study of a longitudinal cohort of patients with
rheumatoid arthritis.
Selecting the right therapy the first time for
patients with RA is a research priority because
very good disease control is only achieved with
etanercept in 30% of patients and other biologic
therapies targeting other pathways besides tumour
necrosis factor are available, wrote researchers led by
Dr Darren Plant of the National Institute for Health
ResearchManchester Musculoskeletal Biomedical
Research Unit at the Manchester (England) Acad-
emy of Health Sciences (Arthritis Rheumatol 2016
Jan 27. doi: 10.1002/art.39590).
Their study selected 72 patients from the
Biologics in Rheumatoid Arthritis Genetics
and Genomics Study Syndicate (BRAGGSS)
longitudinal cohort based on having an extreme
response phenotype after 3 months of treatment
with etanercept. DNA from each patient was
sampled before therapy was initiated.
A total of 36 patients were very good responders
to etanercept and in clinical remission, defined by
having a 28-joint Disease Activity Score (DAS28)
of less than 2.6.
The 36 patients classified as nonresponders to
etanercept had a DAS28 improvement of less than
0.6 or an endpoint DAS28 of greater than 5.1.
Following bisulfite conversion of the DNA, the
research team used the HumanMethylation450
BeadChip to determine unmethylated versus
methylated cytosines in the DNA and found five
differentially methylated sites associated with
response to etanercept that passed the 5% false
discovery rate threshold.
The most compelling evidence for differential
methylation was observed in the LRPAP1 gene
located on chromosome 4. This gene encodes a
chaperone of low density lipoprotein receptor-
related protein 1 (LRP1), which is known to
influence TGF-beta activity.
Four CpG sites within exon 7 of the LRPAP1
gene were more methylated in nonresponders,
results showed.
“The results indicate that DNA methylation
profiling may provide a new biomarker of response
to etanercept in patients with RA,” concluded the
researchers, who said that the study is the first
to investigate the influence of epigenetic varia-
tion on response to biologic therapies. Validation
in a larger independent cohort is needed before
transfer to clinical practice would be possible,
they said.
The results indicate that DNA
methylation profiling may provide a new
biomarker of response to etanercept in
patients with RA.
Patients in the hot-joint cohort had
a nearly fourfold higher risk of x-ray
damage at 1-year follow-up, compared
with those with cool joints.
Vol. 4 • No. 1 • 2016 • Rheumatology News 9
RHEUMATOID ARTHRITIS