What are 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. They are also called targeted therapies.
Biologics for psoriasis
Biologics approved for the treatment of psoriasis include:
- Infliximab (Remicade®)
- Etanercept (Enbrel®)
- Adalimumab (Humira®)
- Ustekinumab (Stelara®)
- Secukinumb (Cosentxy®)
- Ixekizumab (Taltz®)
- Brodalumab (Siliq®)
- Efalizumab (Raptiva®—withdrawn from the market in 2009)
- Alefacept (Amevive®—withdrawn from the market in 2011)
These medications are also used for other severe health problems. Registered indications in New Zealand in January 2015 are shown in the table below.
How do biologics work in psoriasis?
Evidence strongly suggests that psoriasis is a disorder of the immune system. 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-alpha (TNFα) blockers. These work by blocking the activity of TNFα, the primary cytokine involved in psoriasis. Ustekinumab targets interleukin-12 (IL-12) and IL-23. Secukinumb, ixekinumab and brodalumab target IL-17.
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 tuberculosis (TB). Uncommon infections with organisms such as listeria and legionella may be more common and more serious in patients on biologics.
Screening for latent TB should be undertaken prior to commencing a TNFα inhibitor and other biologics.
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, infliximab, adalimumab and etanercept are funded by PHARMAC for some cases of severe psoriasis on Special Authority application.
Vaccinations and biologics
Immunisation status should be reviewed prior to starting biologic treatment. If necessary, vaccines should be updated prior to treatment. Annual influenza vaccination is recommended.
As they may induce illness in immunodeficient individuals, live vaccines should not be used during treatment with biologics. Currently available live attenuated viral vaccines include measles, mumps, rubella, varicella, yellow fever, influenza (intranasal vaccine) and oral polio vaccine. Live attenuated bacterial vaccines include BCG and oral typhoid vaccine.
Monitoring while on biologics
It is recommended that patients on biologic medications should be monitored, and should have routine blood tests at least every 6 months or so, including full blood count and liver function tests. Screening for latent TB should be repeated from time to time.
The future of biologics
Research and development in the field of biologics is very exciting. Drugs under development for treating psoriasis in 2015 include:
- AMG-827 and ixekinumab (IL-17 inhibitors)
- Tofacitinib (a JAK-3 inhibitor)
- Sotrastaurin (a protein kinase inhibitor)
- Certolizumab (a humanized monoclonal antibody used in Crohn disease)
Biologics for other types of skin disease
Other biologics used for severe skin diseases (2015) include:
- Rituximab (Rituxan®), initially used for B-cell lymphoma and now for rheumatoid arthritis and granulomatous polyangiitis
- Anakinra (Kineret®), registered for rheumatoid arthritis but also found to be helpful for autoinflammatory syndromes such as Schnitzler syndrome, cryopyrin associated periodic syndrome and adult Still disease.
- Omalizumab (Xolair®), initially used for asthma and now for chronic spontaneous urticaria
- Several targeted therapies used in metastatic melanoma
Promising biologics under investigation include:
- Abatacept (Orencia®, a monoclonal antibody against CTLA-4, registered for rheumatoid arthritis) for alopecia areata;
- Dupilumab for atopic eczema (Dupixent®).