Psoriasis: Understanding the Burden and Drug Targets

Psoriasis is a chronic, t-lymphocyte mediated inflammatory disease that effects approximately 2-3% of the US population. It is commonly characterized by silvery white erythemous plaques that vary in presentation. Psoriasis was first described by Hippocrates (460-377 BC), making it one of the oldest known skin conditions. Historically the disease and its treatment were profoundly misunderstood—patients were isolated in fear of contaminating others and treated with topical arsenic. To date, significant progress has been made in understanding psoriasis, the burden of the disease and how it is treated. However, challenges remain, as most patients are undertreated or not treated at all.

Psoriasis is widely accepted as a disease of the innate and adaptive immune system. Genetic predispositions accompanied by environmental triggers such as injury to the skin, infection, smoking, and psychogenic stress, may cause an exacerbation of the disease. Severity is assessed by scaling, redness, induration, location, and body surface area (BSA) involvement of the plaque. In many cases, these plaques cause emotional distress to patients, as they can be painful, itchy and debilitating at times.

Although frequently misconceived as solely a cosmetic disease, psoriasis poses clinical challenges outside of its physical presentation. The systemic nature of the inflammation is thought to contribute to the high prevalence of comorbid conditions. Studies have shown that patients with psoriasis have a decreased life expectancy, higher incidence of depression, metabolic disorder and immune mediated disorders (e.g. psoriatic arthritis, multiple sclerosis and Crohn’s disease) when compared to the general population. These findings propose early control of psoriasis may reduce the economic burden of the condition, prevent comorbidities and complications associated with concomitant conditions. As previously stated, patients report being undertreated or not treated at all despite these findings.

Options For Treatment

Lack of appropriate treatment is not due to an absence of effective options. In fact, over the past several years psoriasis therapies have become more targeted and efficacious. The development of interleukin 17 (IL-17) inhibitors, is a notable advancement in treatment for patients with psoriasis. Costentyx (secukinumab) was the first IL-17 inhibitor to come to market in 2015 and was followed by Taltz (ixekizumab) in 2016. Both agents had phase III clinical trial results reported 90% improvement of patient’s psoriasis area severity index (PASI) score in the majority of patients. Clinical trials for ixekizumab had 35-38% of patients obtain a complete response, also referred to as a PASI 100. IL-17 is not the only inflammatory molecule being shown to have great efficacy in treatment of psoriasis. For example, Tremfya (guselkumab) targets IL-23 and Otezla (apremilast) targets phosphodiesterase-4. Availability of effective treatment options is expected to expand.   

These new therapies are redefining psoriasis treatment goals. Traditionally, a 75% improvement in PASI score was recognized as treatment success. Since these newer agents, treatment goals have been redefined since drugs can achieve a higher standard of care for patients. In fact, some clinical trials are now using PASI 90 as their primary outcome.

Recognizing that effective treatments are available raising the discussion as to why patients continue to feel dissatisfied with their treatment. Prescribers should be educated on the importance of adequately treating patients with psoriasis. Access to more effective agents may be limited due to cost. Biologics are typically expensive products, and unfortunately the market has not seen the heavily anticipated cost savings from biosimilars. Additionally, prescribers have been using TNF inhibitors such as Enbrel and Humira for years and therefore may be resistant to trying newer therapies for patients with severe psoriasis or patients who have failed these options.

Psoriasis is much more than a skin condition as it has a systemic inflammatory response. Increased knowledge of the disease burden should encourage providers to more adequately manage this disease state. As advances in understanding the pathophysiology of psoriasis are being made, more efficacious drugs are entering the market providing patients with the opportunity to reduce the severity of their psoriatic plaques and prevent complications due to the inflammatory nature of the disease. Cost and provider acceptance are both significant challenges in adequately managing this disease.