Review of Systemic Treatment of Psoriasis Recommends Biologics

Psoriasis is a life-long disease with a chronic relapsing course, and most patients require long-term management. The evolution of psoriasis is unique and unpredictable in each patient, and can range from mild to very severe; recurrences can occur with varying frequency.

Thus, the successful treatment of psoriasis has a considerable impact on patients’ quality of life. A review by Paolo Gisondi and colleagues in the November 2017 issue of the International Journal of Molecular Sciences discusses the systemic treatment of psoriasis and recommends biologics and biosimilars for long-term treatment of psoriasis because of their better tolerability and safety compared with other systemic treatments, which are limited largely by poor tolerability and cumulative toxicity.

Although the cost of biologics is an issue for sustainability, Gisondi and coauthors believe that biosimilars can be used to help manage the high cost of treatment with biologics, noting that, in some regions, biosimilars of infliximab and etanercept are already available, with adalimumab expected to soon be made available.

The pathogenesis of psoriasis arises from a combination of genetic and environmental risk factors. Psoriasis is T-cell driven, with the Th1 and Th17 cells playing a pivotal role by producing different cytokines including interleukin (IL)-6, IL-17, and IL-22; interferon (IFN)-gamma; and tumor necrosis factor (TNF)-alpha, resulting in increased proliferation of epidural cells, neo-angiogenesis, and infiltration of white cells in the skin. The review explains that some biomarkers can be used to predict treatment outcome with biologics. For example, high body mass index predicts poor response and long-term efficacy to conventional and biological treatments. Specific individual genetic variations in single nucleotides associated with TNF are associated with a higher response rate to etanercept and adalimumab; other genetic variations related to IL predict a higher response to ustekinumab, infliximab, or adalimumab. A faster and higher response to ustekinumab has been confirmed in patients with certain human leukocyte antigens (HLA).

Multiple factors influence disease severity, including disease extent, location of lesions, degree of inflammation, responsiveness to treatment, and impact on quality of life. The indications for systemic treatment are:

• Psoriasis Area and Severity Index (PASI) score greater than 10
• PASI score less than 10 but with the involvement of scalp, face, hands, nails, palmoplantar, or genital area
• Psoriasis associated with severe symptoms that are not controlled by topical treatment
• Severe impact of the disease on quality of life
• Presence of active psoriatic arthritis

The ultimate goal of psoriasis therapy is the complete or almost complete clearing of skin lesions and an improvement of 90% or greater in the PASI. If treatment goals are not achieved, strategies can be adopted such as raising the dose of drug, reducing the time gap between administrations, or combining a drug with another. Changing the drug is indicated when these adjustments are ineffective or not appropriate.

An increased risk of overall infections, including herpes zoster and Candida, is the only major concern associated with treatments using TNF-alpha and IL-17 inhibitors, respectively. Generally, the continuous regimen of biologics has greater efficacy and safety compared with intermittent regimens. Indeed, the risk of adverse effects and/or developing anti-drug antibodies is significantly higher in those patients receiving biologics as an intermittent regimen, the review notes. It has not been fully clarified whether stopping biologic therapy is appropriate in those patients who achieve continuing psoriasis remission, though an international consensus agreed that stopping biologic therapy is not generally recommended.