Rheumatology News

NEWS 4

R heumatology N ews • Vol. 4 • No. 1 • 2016

Family history of cardiovascular disease is key in psoriasis patients

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

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

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

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.

“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.

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

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.