Biologics

Biologics, also known as biologic therapies or biological response modifiers, are drugs derived from living material (human, plant, animal, or micro-organism). They interfere with specific parts of the body's immune system to treat and prevent immune-mediated inflammatory disorders and cancers.

Biologics for psoriasis

Biologics approved for the treatment of psoriasis include:

• Infliximab
• Etanercept
• Adalimumab
• Ustekinumab
• Alefacept (not available in New Zealand)
• Efalizumab (withdrawn from the market in 2009)

These medications are also used for other severe health problems. Registered indications in New Zealand in June 2011 are shown in the table below.

How do biologics work in psoriasis?

Evidence from recent research in psoriasis strongly suggests that this is a disorder of the immune system. Known as an autoimmune disease, this basically means that an individual's immune system starts reacting against his or her own tissue. In this particular instance, abnormally large numbers of T cells (a type of white blood cell) trigger the release of cytokines (chemicals in the body's immune system) that can cause inflammation, redness, itching and flaky skin patches characteristic of psoriasis.

Biologics work by interfering with specific components of the autoimmune response. Unlike general immunosuppressants that suppress the entire immune system, biologics can fight more selectively and target only those chemicals involved in causing psoriasis.

Etanercept, infliximab and adalimumab belong to the class of biological medicines called tumour necrosis factor (TNF) blockers. These work by blocking the activity of TNF-alpha, the primary cytokine involved in psoriasis. Alefacept and efalizumab are T-cell blockers and block the overactive T-cells. Ustekinumab targets interleukin-12 (IL-12) and IL-23.

How are biologics given for psoriasis?

All these biological medicines are given at defined intervals. The interval between doses is dependent on each individual biological medicine. Etanercept, alefacept and efalizumab are usually once weekly, and adalimumab is every two weeks by self-administered subcutaneous injection. Infliximab is given by intravenous infusion at a hospital or clinic, 3 times over a period of 6 weeks and then every 8 weeks.

In many cases, other topical and systemic medications for psoriasis (e.g. methotrexate) may also be prescribed in an attempt to improve efficacy.

Biologic medication are often very effective in psoriasis. However, in some cases, they lose their effectiveness after a period of time (secondary failure) and other treatment may be required.

What are the possible side effects of biologics?

To date, biologics for psoriasis appear to have very few side effects. Because of their precise targets, they appear not to damage the entire immune system the way that general immunosuppressants do. However, biologics should still be considered immunosuppressive and may increase the risk of infection and reactivation of TB. Uncommon infections with organisms such as listeria and legionella may be more common and more serious in patients on biologics.

They also may increase the risk of skin cancer, especially squamous cell carcinoma (SCC) and some lymphomas.

When should biologics be used?

Due to the high cost of these medicines, their use is limited to patients with moderate to severe psoriasis where:

• all other treatments have failed
• side effects of other treatments become intolerable or toxicity has occurred
• concurrent diseases such as congestive heart failure or liver disease preclude the use of currently available systemic therapies.

In New Zealand, adalimumab and etanercept are funded by PHARMAC for some cases of severe psoriasis on Special Authority application. Infliximab is provided by some District Health Boards under certain circumstances.

The future of biologics

Research and development in the field of biologics is very exciting. Drugs under development for treating psoriasis include:

• AMG-827, secukinumab and ixekinumab (IL-17 inhibitors)
• Apremilast, an oral PD-4 inhibitor
• Tofacitinib (a JAK-3 inhibitor)
• Sotrastaurin (a protein kinase inhibitor)
• Certolizumab (a humanized monoclonal antibody used in Crohn’s disease)

Biologics for other types of skin disease

Other biologics used for severe skin diseases (2011) include:

• Rituximab, initially used for B-cell lymphoma and now for rheumatoid arthritis and Wegener granulomatosis
• Ipilimumab, used for metastatic malignant melanoma
• Anakinra, registered for rheumatoid arthritis but also found to be helpful for autoinflammatory syndromes such as Schnitzler syndrome, cryopyrin associated periodic syndrome and adult Still's disease.

New biologics under investigation includ abatacept (registered for rheumatoid arthritis) for alopecia areata (a monoclonal antibody against CTLA-4) and omalizumab for chronic urticaria.