Biological Agents Used to Treat Psoriasis

Psoriasis is a chronic inflammatory skin disease, commonly characterized by plaques of scaly skin on various parts of the body. The rash in psoriasis may consist of small or large areas, and it may appear as one of many different subtypes of psoriasis (for example nail or scalp psoriasis). Psoriasis affects people of all ages, and close to 1% of the population, with at least 4.5 million adults afflicted in the United States.^[1] Due to the unique ways that psoriasis appears in different patients, there is a broad range of treatments for psoriasis.

Current topical treatment modalities include steroids, tars, vitamin D derivatives, retinoids, and phototherapy. For patients with severe psoriasis, systemic medications may be necessary for treatment and include both oral and injected medications. The use of focused ultraviolet light, known as narrowband ultraviolet phototherapy, is used in psoriasis that is more widespread in the body. In some cases, systemic medications are necessary when the topical and phototherapy options are not working adequately for the skin or if psoriasis involves the joints, known as psoriatic arthritis. Some examples of systemic medications include oral and injected methotrexate, oral retinoids, oral cyclosporine, oral apremilast, and biologic therapy.^[2]

What Are Biologic Therapy Agents? 

Biologic therapy agents are a relatively new class of medications that are rapidly gaining popularity in managing moderate to severe psoriasis. These agents work by suppressing the immune system, which plays a central role in psoriasis. The names of biologic agents that are approved to treat psoriasis include etanercept (Enbrel®), adalimumab (Humira®), infliximab (Remicade®), ustekinumab (Stelara®) and secukinumab (Cosentyx®). These medications are given as an injection or through an IV. Some of the medications allow for self-injection while others need to be infused through an IV (see table below).

Biologics are now frequently used if other oral agents are not effective, or there are contraindications to using traditional oral medications. In contrast to some of the other systemic psoriasis medications, such as methotrexate and cyclosporine, biologic agents can have a lower side effect profile. They can also improve symptoms of psoriasis-associated arthritis. Biologics are not taken daily and therefore might be more convenient to take for some people.  However, there are certain risks and side effects associated with biologics that should be considered when deciding if this is a good type of therapy for you.

Biological Agents for Psoriasis

Mechanisms of Biologic Agents to Treat Psoriasis

Overall, biologic agents act on more specific parts of the immune system compared to older drugs. A theoretical advantage exists with specificity because there are potentially fewer side effects and more effective results.

There is scientific evidence showing that a subtype of immune cells, called T-cells, are inappropriately activated in psoriasis and accumulate in the skin, contributing to the inflammation associated with psoriasis.^[3] Immune cells can communicate with one another through a messenger molecule called TNF-alpha. This molecule promotes inflammation and leads to a more robust inflammatory response. Etanercept, infliximab, and adalimumab work by inhibiting TNF-alpha. TNF-alpha inhibitors are associated with risk for reactivation of tuberculosis and other rare infections; however, it was established that the benefit of these drugs far outweighs the risks for most people.^[4]

IL-17 and IL-23 inhibitors are the most recently approved biologic agents for psoriasis and work by blocking different molecules called interleukins, which are inflammatory signals. Ustekinumab and secukinumab target IL-12/23 and IL-17 receptor, respectively. The newer IL-23 specific inhibitors include guselkumab and tildrakizumab. These molecules are involved in T-cell communication and activation. These newer agents are even more specific compared to the TNF- alpha inhibiting medications and are still being carefully monitored for long-term safety.^[5]  

Limitations

One drawback to biologic agents is cost. Biologics are very expensive, costing around $20,000 per year per patient or more, which greatly limits the number of patients who can use them.^[6] Additionally, injection and IV administration make taking these medications more difficult than topical or oral medications. Patients who have severe infections or are immunosuppressed may not be candidates for biologic medications. At this time, biologics for children are not approved in the United States for treatment of psoriasis (but are used by physicians “off label”); although, etanercept is approved in Europe for children with psoriasis ages 8 to 17. 

Psoriasis can significantly impact quality-of-life and has been linked to depression, anxiety, and an overall negative effect on daily life.^[7] Over 30% of people with psoriasis have moderate to severe forms of the disease, necessitating the use of systemic therapies.^[8] Progress in psoriasis research and the emergence of biologic agents offers hope to patients afflicted with psoriasis who are in need of new medications.