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Family history of cardiovascular disease is key in psoriasis patients
BY BRUCE JANCIN
Frontline Medical News
At the EADV congress, Copenhagen
T
he increased risk of MI and stroke in
patients who develop psoriasis as young
adults is essentially confined to those
having a positive family history of cardiovas-
cular disease, according to a Danish national
study presented at the annual congress of
the European Academy of Dermatology and
Venereology.
“We found a significantly increased risk of
MACE [major adverse cardiovascular events]
in patients with psoriasis only when a fam-
ily history of cardiovascular disease was pre-
sent. This just highlights why it’s important
that future studies of cardiovascular risk in
psoriasis should include family history. Also,
an increased focus on cardiovascular disease
in relatives may be appropriate in the car-
diovascular risk assessment of patients with
psoriasis,” said Dr Alexander Egeberg of the
University of Copenhagen.
He presented a population-based study
involving 15 years of follow-up of 30,278
Danes diagnosed with psoriasis in their 20s
and a control group consisting of nearly 2.7
million of their Danish contemporaries who
were not. None had personal history of acute
MI or stroke at baseline. Family medical his-
tory, including whether cardiovascular disease
occurred in first-degree relatives, was available
for all subjects.
Dr Egeberg and coinvestigators mapped
the incidence of acute MI, ischaemic stroke,
or cardiovascular death in psoriasis patients
and the general population controls during
follow-up.
“When you look at the patients who devel-
oped psoriasis and didn’t have a positive fam-
ily history of cardiovascular disease, there are
almost no cardiovascular events for the entire
country,” Dr Egeberg observed.
In contrast, in a multivariate analysis
adjusted for age, gender, socioeconomic status,
comorbid cardiovascular disease, smoking, and
the use of cardiovascular medications, patients
with mild psoriasis and a positive family history
for cardiovascular disease had a 28% greater
risk of a premature cardiovascular event than
the general population during follow-up out to
roughly age 40. Those with a positive family
history and severe psoriasis as defined by the
use of systemic therapies had a 62% increase
in risk. Both of these elevated risks were sta-
tistically significant.
Among young adult Danes with a positive
family history for cardiovascular disease, there
were 222MACE events during 62,225 person-
years of follow-up in the mild psoriasis group
and 31 events during 6848 person-years in
the 4504 subjects with severe psoriasis. The
resultant incidence rates in both groups were
significantly higher than in the control group,
who experienced 28,846 MACE events during
16.1 million person-years of follow-up.
In contrast, fewer than 10 MACE events
occurred in Danish psoriasis patients without
a family history of cardiovascular disease.
A positive family history was also associated
with increased MACE in the nonpsoriatic
general population, although it didn’t confer
as great a risk as in the Danes with psoriasis.
A point worthy of consideration, Dr Egeberg
noted, is that the epidemiology of psoriasis in
Denmark apparently differs in several impor-
tant ways from psoriasis in the US and some
other countries. For one, the prevalence is
higher in Scandinavian countries – 7.1% in
a Danish national cross-sectional study (
Int
J Dermatol
2013;52:681–3) and 8% in neigh-
bouring Norway – as compared with 2–3% in
much of the rest of the world.
Moreover, according to the same cross-sec-
tional study, the prevalence of traditional car-
diovascular risk factors, such as smoking and
the components of the metabolic syndrome,
isn’t higher in Danish psoriasis patients than in
the country’s general population. That’s in con-
trast to the situation in the United Kingdom,
where Dr Joel M. Gelfand of the University of
Pennsylvania and associates reported a decade
ago in a landmark study that the prevalence of
hypertension, obesity, hyper lipidaemia, dia-
betes, and smoking were all higher in persons
with psoriasis than in the general population.
Similar findings were subsequently reported
in US psoriasis patients.
Despite their absence of elevated levels
of the standard cardiovascular risk factors,
Danish psoriasis patients as a group do face a
clinically significant increase in cardiovascular
risk, compared with the general population, as
shown in yet another Danish national cohort
study in which the rate ratios for cardiovas-
cular death for mild and severe psoriasis were
1.14 and 1.57, respectively, compared with
controls.
In an even more recent Danish nationwide
study, the overall death rate was found to be
25.4 per 1000 person-years in patients with
severe psoriasis, 17.0 in those with mild pso-
riasis, and 13.8 per 1000 person-years in the
general population.
Dr Egeberg said his new Danish findings
suggest that even in psoriasis patients with a
greater burden of systemic inflammation as
expressed in severe disease, that burden alone
doesn’t translate into increased cardiovascular
risk. Rather, elevated cardiovascular risk ap-
pears to be a consequence of heritable factors,
Dr Egeberg said.
An important caveat regarding this study,
he continued, is that the mean age at which
participants were diagnosed with psoriasis
was 26.6 years. It’s unclear whether the study
findings extend to individuals who develop the
dermatologic disease later in life.
Dr Egeberg reported having no financial con-
flicts regarding this study, supported by Danish
national research funding.
Etanercept during pregnancy doubles the
odds of major malformations
BY M. ALEXANDER OTTO
Frontline Medical News
At the American College of Rheumatology
annual meeting, San Francisco
E
tanercept during pregnancy more
than doubled the risk of major
congenital malformations in a
study by the Organization of Teratol-
ogy Information Specialists.
The group keeps a prospective
registry on exposures to biologics
during pregnancy. It is finishing up
its adalimumab investigation and
hasn’t found much to worry about,
and continues to gather data on
abatacept, tocilizumab, tofacitinib,
apremilast, and certolizumab pegol.
Etanercept , however, seems to
be a different story; major malfor-
mations turned up in the group’s
recently completed investigation.
Even so, Organization of Teratology
Information Specialists (OTIS) in-
vestigator Dr Christina D. Chambers,
PhD, of the University of California,
San Diego, was careful to note at
the annual meeting of the Ameri-
can College of Rheumatology that
“etanercept is not meeting the crite-
ria for causality. There’s no pattern”
in major defects and “no biological
plausibility” because the drug doesn’t
seem to cross the placenta when the
fetus is most vulnerable to adverse
outcomes.
“It is difficult to draw the con-
clusion that this drug is causing
harm. With true teratogens, you
tend to see reduced birth weights
and an increased risk of spontane-
ous abortion, which is not the case
with etanercept. We are seeing only
this one finding that kind of stands
alone, and everything else looks
pretty good,” she said.
The etanercept study investigated
pregnancy outcomes in 370 women
exposed to the drug while pregnant,
mostly women with rheumatoid ar-
thritis, but also women with psoriasis
and ankylosing spondylitis. Their
outcomes were compared with 164
pregnant women with the same
diseases but no etanercept exposure
– the disease control group – and 296
healthy pregnant women.
Women in all three groups were
about 33 years old on average, and
about 80% were white. The women
were enrolled toward the end of
their first trimester. Disease severity,
comorbidities, and use of vitamins,
alcohol, and tobacco were similar be-
tween etanercept and disease control
women. About 40% of the etanercept
and disease control women, but just
one in the healthy pregnancy group,
were exposed to systemic corticoster-
oids while pregnant.
There were 33 major structural de-
fects in children born towomen taking
etanercept versus 7 in the disease con-
trol group. That translated to a more
than doubling of risk with etanercept
(odds ratio, 2.37; 95% confidence
interval, 1.02–5.52), and a more than
doubling of risk versus the 10 major
structural defects in children born to
healthy control women (OR, 2.91;
95% CI, 1.37–6.76).
A subanalysis excluded chro-
mosomal anomalies, but “did
not [change] our conclusions,”
Dr Chambers said.
Major structural defects generally
refer to problems that need a surgical
fix, including spina bifida, atrial sep-
tal defects, cleft palates, hypospadias,
polydactyly, and craniosynostosis.
Minor defects that don’t need sur-
gery, like a missing earlobe, occurred
in six children exposed to etanercept
and showed two different patterns
that involved “three specific minor
malformations” not seen in either
of the control groups, Dr Chambers
said. She did not elaborate on what
those patterns were, but noted that
the parents usually had them, too,
“suggesting a genetic component as
opposed to a drug effect.”
Children in the three study groups
had no statistically significant dif-
ferences in 1-year malignancy rates,
serious infections, and hospitalisa-
tions, even when exposed to etaner-
cept in the third trimester.
Children exposed to etanercept,
however, were more likely to be born
preterm and more likely to be small
for gestational age in weight, length,
and head circumference. They
were also more likely than disease
control children to screen positive
for developmental issues at 1 year,
but none of those differences were
statistically significant.
Dr Chambers disclosed funding from
14 companies, including Amgen,
the maker of etanercept, and Jans-
sen, Pfizer, Roche, Sanofi/Genzyme,
GlaxoSmithKline, and AbbVie, the
maker of adalimumab.
R
heumatology
N
ews
• Vol. 4 • No. 1 • 2016
NEWS
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