VANCOUVER, B.C. – Results from some studies have concluded that treatment with conventional systemic or biologic therapy improves the elevated risk of cardiovascular disease in patients with psoriasis, but the association is not yet definitive, according to Dr. Robert Kalb.
"Current evidence is suggestive, but certainly our patients with psoriasis need intensive management of cardiovascular risk factors and appropriate psoriasis therapy, which may also produce benefits from a cardiovascular standpoint," Dr. Kalb said at the annual meeting of the Pacific Dermatologic Association.
Dr. Robert Kalb
Researchers who conducted the earliest study to explore the association between psoriasis and increased risk for cardiovascular death found that when they controlled for risk factors including age, sex, smoking, diabetes, hypertension, and hyperlipidemia, having psoriasis led to a hazard ratio of 1.57 for cardiovascular death (Eur. Heart J. 2010;31:1000-6). Since that time, six meta-analyses have appeared in the medical literature showing that psoriasis is linked to an increased risk of cardiovascular disease. Most of these studies defined severe psoriasis as patients who had received a systemic agent. Body surface area or other objective measures of psoriasis were not part of the definition, said Dr. Kalb, a dermatologist in group practice in Buffalo.
Emerging evidence supports the idea that increased risk factors are associated with the severity of psoriasis. As part of the landmark Incident Health Outcomes and Psoriasis Events (iHope) study, investigators found that patients with disease affecting 10% or more body surface area had an increased risk of myocardial infarction. One study defined psoriasis severity by body surface area (JAMA Dermatol. 2013;149:1173-9). The investigators found that the burdens of MI and other comorbid diseases increase with increasing disease severity, particularly in those with 10% body surface area or more affected.
Investigators are also working to determine if systemic therapy reduces the risk of MI in psoriasis patients. The Consortium of Rheumatology Researchers of North America (CORRONA) registry database found that in patients with rheumatoid arthritis, anti–tumor necrosis factor (TNF) agents reduced the risk of cardiovascular events (HR, 0.39), compared with nonbiologic disease-modifying antirheumatic drugs. Methotrexate did not reduce the risk of cardiovascular events, while the use of prednisone increased the risk (Ann. Rheum. Dis. 2011;70:576-82). Another review showed that anti-TNF therapy decreased the risk, but the use of methotrexate decreased the risk slightly more (Rheumatology 2011;50:518-31). "Reassuringly, there was no increased risk of congestive heart failure, which has always been [included] in the label of [anti-]TNF agents," Dr. Kalb said.
A cohort study of 25,554 patients with moderate to severe psoriasis used U.S. administrative and pharmacy claims data to examine the risk of acute myocardial infarction in those who underwent systemic therapy, compared with those who underwent phototherapy. The investigators found a trend toward an increased risk of MI in those who received systemic therapy, but there were no significant differences in risk between the two treatment groups (Br. J. Dermatol. 2011;165:1066-73). On the other hand, a retrospective, longitudinal cohort study of 2,400 patients with severe psoriasis in Denmark showed that the use of biologic agents and methotrexate was associated with fewer cardiovascular events (hazard ratios, 0.48 and 0.50, respectively), but the use of other antipsoriatic therapies – including cyclosporine, retinoids, phototherapy, and topicals – were not (J. Intern Med. 2013;273:197-204).
A retrospective cohort study of 8,845 Kaiser Permanente psoriasis patients set out to determine whether treatment with TNF inhibitors was associated with a decreased risk of MI, compared with those who did not receive TNF inhibitors (Arch. Dermatol. 2012;148:1244-50) . After adjusting for MI risk factors, the researchers found that those who received TNF inhibitors had a significantly lower risk of MI, compared with those who received topical therapy (adjusted HR, 0.50).
"Why do different studies reach different conclusions?" Dr. Kalb asked. "Different populations were studied, and there were differences in terms of how reference groups were defined and in the methods for categorizing therapy and severity of disease. Data from population studies are not yet sufficient to determine whether [anti-]TNF agents will reduce the incidence of MI."
One conundrum for researchers is how to measure this decreased risk. "What surrogate markers should we use?" Dr. Kalb asked. "One study showed a significant decrease in CRP [C-reactive protein] and ESR [erythrocyte sedimentation rate] in patients receiving therapy. The gold standard of decrease in mortality in this type of study will not be done because it requires thousands of patients studied over at least 10 years." However, in cardiology, 18-fluorodeoxyglucose PET scanning shows decreased inflammation in patients taking statins. Whether the same effect can be shown in psoriasis patients taking systemic medications for their disease remains unknown, but prospective studies are ongoing.