PDE4 Inhibitors for Psoriasis: What to Know

Plaque psoriasis is a chronic autoimmune condition. That is, the immune system mistakenly attacks the body. It causes red, scaly patches to develop on the skin. These patches may sometimes feel very itchy or painful.

Treatment options aim to reduce these symptoms. Because inflammation is at the root of plaque psoriasis, the goal of many medications is to lessen this immune system response and create a normal balance.

If you’re living with moderate to severe plaque psoriasis, a PDE4 inhibitor may be an effective tool in managing symptoms.

However, the medication isn’t for everyone. You should discuss your treatment options with your doctor.

PDE4 inhibitors are a relatively new treatment. They work to suppress the immune system, which reduces inflammation. They act at the cellular level to halt the production of an overactive enzyme called PDE4.

Researchers know that phosphodiesterases (PDEs) degrade cyclic adenosine monophosphate (cAMP). cAMP contributes significantly to signaling pathways between cells.

By stopping PDE4s, cAMP increases.

According to a 2016 study, this higher rate of cAMP may have anti-inflammatory effects, specifically in people living with psoriasis and atopic dermatitis.

PDE4 inhibitors, like apremilast (Otezla), work inside the body to prevent inflammation.

As a preventive measure, it may be beneficial for people with psoriasis to manage inflammation. Reducing inflammation may cause outbreaks to be less frequent and less severe.

It also may stall or prevent disease progression to result in psoriatic arthritis (PsA).

Of those living with any kind of psoriasis, about 30 percent eventually develop PsA, which causes mild to severe joint pain. PsA can reduce your quality of life.

Apremilast, a PDE4 inhibitor, is taken by mouth. It also acts on an important pathway by interrupting the inflammatory response that contributes to the symptoms of plaque psoriasis.

Biologic treatments such as adalimumab (Humira), etanercept (Enbrel), and infliximab (Remicade) are injected into the body.

Other injectable biologic treatments include:

• Ustekinumab (IL-12/23 inhibitor)
• secukinumab (IL-17A inhibitor)
• ixekizumab (IL-17A inhibitor)
• guselkumab (IL-23 inhibitor)
• risankizumab (IL-23 inhibitor)

Tofacitinib is a Janus kinase (JAK) inhibitor that’s approved as an oral treatment.

Abatacept is a T-cell activation inhibitor that’s given as an intravenous (IV) infusion or an injection.

Apremilast is recommended for people living with moderate to severe plaque psoriasis who are also candidates for systemic therapy or phototherapy.

In

Although PDE4 inhibitors show great promise, they’re not for everyone. Apremilast hasn’t been tested in pregnant or breastfeeding women. Currently, it’s only approved for adults.

It’s also important to weigh the potential risks and benefits of PDE4 inhibitors.

Apremilast comes with some known risks.

People taking apremilast may experience reactions such as:

• nausea
• diarrhea
• upper respiratory tract infection
• headache

Some people also experience significant weight loss.

Apremilast can also increase feelings of depression and thoughts of suicide.

For people with a history of depression or suicidal behavior, it’s recommended that they talk to their doctor to help them carefully weigh the potential benefits of the drug against the risks.

If you do experience side effects, your doctor may recommend stopping the medication.

Psoriasis is a chronic — but manageable — condition. The role inflammation plays is the focus of treatment and research.

If your doctor determines your plaque psoriasis is mild or well managed, they may recommend nonsteroidal anti-inflammatory drugs (NSAIDs). They may also recommend topical treatments.

They’ll most likely try both of these recommendations before considering the use of a PDE4 inhibitor or other immune modulators.

Researchers have discovered more about the mechanisms in the body that cause inflammation. This information has helped in the development of new medications that may provide relief for those living with psoriasis.

PDE4 inhibitors are the latest innovation, but they come with risks. You and your doctor should carefully consider these factors before beginning a new type of treatment.