Biologics have revolutionized psoriasis treatment over the last two decades. These targeted immunomodulatory therapies act directly on the cytokine pathways that are upregulated in psoriasis and other autoimmune diseases. Two major classes make up biologics in psoriasis treatment: tumor necrosis factor (TNF) inhibitors and interleukin (IL) inhibitors.
TNF inhibitors became the first available biologic therapies for the treatment of psoriasis.
With one TNF inhibitor, etanercept, nearly half of all patients in a phase III study achieved PASI 75 — a gold standard in measuring psoriasis treatment success — after 12 weeks, compared to four percent in the placebo group. This therapy is self-injected twice per week.
Infliximab is another commonly used TNF inhibitor. During one phase III study, nearly 80 percent of patients achieved PASI 75 after 23 weeks of treatment. This product does have the drawback of needing to be administered intravenously.
One phase III trial comparing adalimumab to methotrexate — a standard immunosuppressive drug with potentially serious side effects used in severe psoriasis treatment — found significantly greater efficacy with 80 percent of patients achieving PASI 75 after 16 weeks on adalimumab. This treatment is self-administered via subcutaneous injection once every other week.
Newer biologics have been designed to target interleukins, another group of cytokines involved in psoriasis pathogenesis.
Ustekinumab is a monoclonal antibody targeting a protein subunit common to IL-12 and IL-23. Trials have found superior efficacy compared to TNF inhibitors. PASI 75 is achieved in roughly 70 percent of patients after just 12 weeks of dosing. Additionally, maintenance therapy injections are needed only once every three months.
Targeting IL-17, secukinumab is approved for adults with moderate to severe plaque psoriasis involving large parts of the body, as well as for active psoriatic arthritis and ankylosing spondylitis. Clinical trials showed a PASI 75 response of nearly 80 percent after 12 weeks and 70 percent with a PASI 90 after 16 weeks. Maintenance therapy is given every four weeks.
Ixekizumab is a humanized anti-IL-17 monoclonal antibody approved for adults with moderate to severe plaque psoriasis. One early phase II study found significant improvements in Dermatology Life Quality Index scores and no serious adverse events, as well as efficacy in difficult-to-treat areas, such as the scalp and fingernails. Later phase III trials showed nearly 90 percent of patients achieving PASI 75 after 12 weeks. Treatment with ixekizumab is given every two weeks.
As a target of IL-17 receptor A, brodalumab was approved by the FDA in February 2017. It is a human monoclonal antibody indicated for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy and have failed to respond to other available systemic therapies. One phase III trial found 83 percent of patients achieved a PASI 75 after three months. However, this therapy does come with a black box warning for suicidal ideation and behavior, as four patients committed suicide during clinical trials. In the United States, brodalumab is only available through a restricted Risk Evaluation and Mitigation Strategy program.
The Future of Biologics in Psoriasis Treatment
While often successful, there is a high degree of variability in individual response to biologics and an associated high cost of treatment. Further research to both produce new treatments and methods of predicting patient response may address these issues. By finding the right treatment for each patient before initiating therapy, further research can help to reduce cost, time, and unnecessary adverse events.