Treating Psoriasis with Biologic Agents

Miami Beach—According to a consensus statement by the American Academy of Dermatology (AAD), biologic agents may be considered among the options for first-line treatment, along with systemic therapies or phototherapy, for patients with moderate-to-severe plaque psoriasis as well as patients with psoriasis that affect various parts of the body or when ≥5% of the skin surface is involved. Despite this recommendation, a National Psoriasis Foundation survey published in 2007 found that patients with moderate-to-severe psoriasis are not adequately treated, with over one third of patients not receiving treatment and even fewer patients receiving systemic therapy, biologic treatments, or phototherapy [J Am Acad Dermatol. 2007;57(6):957-962].

Highlighting the underuse of biologic treatments to treat psoriasis, Ronald Prussick, MD, clinical assistant professor at George Washington University, provided an overview at the recent AAD meeting on the need for effective treatment of psoriasis and the integral role biologic treatments play in treating both psoriasis and associated comorbidities.

Psoriasis and Associated Comorbidities
Dr. Prussick said the need for effective and successful treatment goes beyond just treating the skin changes that characterize psoriasis. Studies have shown that psoriasis can adversely affect daily activities and job performance, and its impact on physical functioning has been found to be similar to that of other serious diseases such as congestive heart failure, chronic lung disease, and arthritis. In addition, people with psoriasis are at increased risk of depression and cardiovascular disease.

Although the link between the skin changes characterizing psoriasis and comorbid conditions remains unclear, scientific data are emerging that support the existence of comorbid conditions in patients with psoriasis. Among these data are findings that show a higher prevalence of metabolic syndrome in people with plaque psoriasis than in people without psoriasis.

Dr. Prussick presented data from a study by Sommer et al [Arch Dermal Res. 2006;298:321-328], which found that patients with plaque psoriasis hospitalized for severe disease or disease resistant to treatment had a significantly higher prevalence of metabolic syndrome compared with hospitalized patients without psoriasis (controls) (4.3% vs 1.1%; P<.0001), as well as diabetes type 2 (11.7% vs 5.8%; P<.0001), hypertension (21.9% vs 10.2%; P<.0001), hyperlipoproteinemia (5.2% vs 2.8%; P<.01), and coronary heart disease (5.5% vs 3.6%; P<.05).

Other data also show a higher prevalence of obesity in people with psoriasis, as well as increased risk of myocardial infarction in younger patients with severe psoriasis.

Along with highlighting the increased risk for these comorbidities, Dr. Prussick also highlighted the risk of mortality in patients with psoriasis citing 1 study that showed women and men with severe psoriasis died 4.4 years and 3.5 years, respectively, before patients without psoriasis [Arch Dermatol. 2007;143:1493-1499].

Biologic Therapies
The rationale of using biologic therapies to treat psoriasis, as well as these associated comorbid conditions, is based on their effectiveness in targeting the mechanisms of disease—in particular, targeting the activity of T-lymphocytes and/or cytokines responsible for the inflammatory nature of the disease. Several studies have demonstrated the efficacy of tumor necrosis factor (TNF) inhibitor therapies to treat various comorbidities, including obesity with type 2 diabetes [J Vasc Res. 2005;42:517-525], metabolic syndrome [Arch Intern Med. 2006;166:902-908], vascular function [Clin Exp Rheumat. 2006;204:309-312; Circulation. 2002;106:2184-2187], and insulin resistance [Clin Exp Rheumatol. 2006;24:83-86].

The biologic agents currently available to treat psoriasis are shown in the table.

T-Cell Inhibitors. As the first biologic agent approved by the US Food and Drug Administration for the treatment of psoriasis, the T-cell inhibitor alefacept has been shown to be effective and safe. Data show that responders may have prolonged remission of 9 to 10 months, and up to 6 years of safety data show no serious safety concerns along with no increased risk of infection or malignancy. Among the advantages of this drug, according to Dr. Prussick, is that it can be used in people with contraindications to TNF-alpha antagonists and can be administered in multiple courses and in addition to other treatments. Disadvantages include a lower response rate than TNF antagonists, delayed effects and variable patient response, immunosuppression, and lack of effectiveness for arthritis associated with psoriasis.

TNF Receptor Antagonists. All 3 agents in this category have shown efficacy in treating psoriasis. However, safety issues include serious infections, opportunistic infections including tuberculosis, malignancies including lymphomas, and demyelination. According to Dr. Prussick, candidates not eligible for TNF therapy include those with a medical history of chronic infections, unstable diabetes, malignancy, demyelination/neurologic diseases, hepatitis B, cardiac failure, psoralen plus ultraviolet A therapy/squamous cell carcinoma, or a family history of multiple sclerosis or lymphoma. For those patients treated with these agents, Dr. Prussick recommended monitoring through a number of tests (comprehensive metabolic profile, complete blood count, antinuclear antibody, C-reactive protein, HIV, hepatitis B, and pregnancy).

Anti–interleukin-12/23 p 40 Antagonists. Currently, phase 2 data show that patients with moderate-to-severe psoriasis treated with these agents show response compared with placebo. Phase 3 randomized trials are needed.

Biologic Agents Are Effective
Based on the current data, Dr. Prussick emphasized that biologic agents are effective in treating psoriasis and can also treat the “whole” disease and possibly reduce comorbidities. Although he said that continuing long-term data are needed to fully assess the safety of these agents, he stressed that multiple options are available to treat patients and that a lack of response to one biologic agent may not preclude successful treatment with a different biologic agent. The goal, or art, he said, “is to make the best match between the patient and the drug.”—Mary Beth Nierengarten