Meta-analyses clarify psoriasis comorbidities

New York - As research begins to clarify the relationship between severe psoriasis and comorbidities such as heart disease and metabolic syndrome, additional questions arise, according to a clinician.

In psoriasis, says Robert E. Kalb, M.D., “The hot topic is the relationship of psoriasis to comorbidities including diabetes, hypertension and cardiovascular disease.” He is a clinical professor of dermatology at the State University of New York, Buffalo, N.Y.

To date, he says, six separate meta-analyses have concluded that psoriasis is an independent risk factor for cardiovascular disease.^1-6 One such analysis included nine studies representing nearly 220,000 patients with mild or severe psoriasis. Investigators ultimately found that mild psoriasis was associated with a significantly increased relative risk (RR) of myocardial infarction (1.29; 95 percent confidence interval/CI: 1.02 to 1.63) and stroke (RR: 1.12; 95 percent CI: 1.08 to 1.16). Severe psoriasis was associated with a significantly increased risk of cardiovascular mortality (RR: 1.39; 95 percent CI: 1.11 to 1.74), myocardial infarction (RR: 1.70; 95 percent CI: 1.32 to 2.18) and stroke (RR: 1.56; 95 percent CI, 1.32 to 1.84).¹

Similarly, another meta-analysis revealed an odds ratio of 1.28 (95 percent CI: 1.18 to 1.38) for cardiovascular events in psoriatic patients versus non-psoriatic controls.²

In light of these data, Dr. Kalb says, “One of the issues we’re facing is, does treatment for the psoriasis improve any of these cardiovascular risk factors? If you treat with methotrexate or the TNF (tumor necrosis factor) inhibitors, for example, will you reduce the patient’s risk of having a heart attack?”

In this regard, he says, early data suggest this might be the case. For example, a retrospective cohort study involving more than 8,000 health plan members showed that treatment with oral agents or phototherapy yielded an odds ratio for myocardial infarction of 0.57 compared to treatment with topical agents, and an odds ratio of 0.45 for treatment with TNF inhibitors versus topicals (P<0.001 in both analyses).⁷ However, he says, it’s too soon to draw any definitive conclusions in this area.

‘Aggressive management’

It’s also important to clarify that the comorbidities mentioned above - especially cardiovascular disease - only affect patients with severe psoriasis, or psoriasis covering 10 percent or more of the body surface area, he says.

Accordingly, “Patients with severe psoriasis need aggressive management of their underlying risk factors.” This could involve treatment of hypertension and hyperlipidemia, plus weight management and smoking cessation, to name a few interventions, Dr. Kalb says. “And certainly they need psoriasis treatment. It may turn out that it also helps their cardiovascular risk factors.”

Additionally, a prospective, randomized study investigated the effect of controlled weight loss on psoriasis severity. Investigators enrolled 60 overweight or obese patients (body mass index: 27-40). Half of them followed a low-energy diet (800 to 1,000 kcal daily) for eight weeks, followed by eight weeks of normal food intake (1,200 kcal daily).

After 16 weeks, median psoriasis area and severity index (PASI) score in the low-calorie group had declined from 5.4 at baseline to 3.4 (P=0.06).⁸

“Investigators were looking for a PASI decrease of three points for statistical significance. But the study did show statistically significant improvements in Dermatology Life Quality Index (DLQ I) scores, blood sugars and insulin levels,” Dr. Kalb says. For example, median DLQ I score dropped two points (P=0.02).

Ustekinumab efficacy

In early October, the Food and Drug Administration approved ustekinumab for psoriatic arthritis. Previously, he says, “The two main treatments for psoriatic arthritis were methotrexate and the TNF blocking agents.” In phase 3 clinical trials, the proportions of patients who received ustekinumab doses of 90 mg and 45 mg who experienced a 20 percent reduction in American College of Rheumatology symptoms (ACR 20) were 50 percent and 42 percent, respectively.⁹

“It’s hard to compare studies, but ustekinumab was about 10 percent less effective than the TNF agents. That’s still definitely efficacious,” Dr. Kalb says. As such, he says that ustekinumab may prove helpful for patients with psoriatic arthritis who do not respond to, or lose response to, TNF inhibitors and methotrexate.

Disclosures: Dr. Kalb is a speaker, consultant and investigator for Abbott and Janssen, an investigator for Amgen, and a consultant for Leo and Taro. He also serves on dermatology safety monitoring boards for Eli Lilly and Apopharma.

References

1 Armstrong EJ, Harskamp CT, Armstrong AW. J Am Heart Assoc. 2013;2(2):e000062
2 Pietrzak A, Bartosińska J, Chodorowska G, et al. Int J Dermatol. 2013;52(2):153-162
3 Gaeta M, Castelvecchio S, Ricci C, et al. Int J Cardiol. 2013;168(3):2282-2288
4 Samarasekera EJ, Neilson JM, Warren RB, et al. J Invest Dermatol. 2013;133(10):2340-2346
5 Xu T, Zhang YH. Br J Dermatol. 2012;167(6):1345-1350
6 Horreau C, Pouplard C, Brenaut E, et al. J Eur Acad Dermatol Venereol. 2013;27 Suppl 3:12-29
7 Wu JJ, Poon KY, Channual JC, Shen AY. Arch Dermatol. 2012;148(11):1244-1250
8 Jensen P, Zachariae C, Christensen R, et al. JAMA Dermatol. 2013;149(7):795-801
9 McInnes IB, Kavanaugh A, Gottlieb AB, et al. Lancet. 2013;382(9894):780-789