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What Everyone with PsO Needs to Know About PDE4 Inhibitors

Medically reviewed by Brenda B. Spriggs, MD, MPH, FACP on February 1, 2018Written by Catherine Lovering on February 1, 2018
need 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 stop this immune system response.

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

Importance of reducing inflammation

Plaque psoriasis is just one kind of psoriasis. Of those living with any kind of psoriasis, about 30 percent eventually develop psoriatic arthritis. Psoriatic arthritis causes mild to severe joint pain. It can reduce your quality of life.

As a preventive measure, it may be beneficial for people with psoriasis to control inflammation. Reducing inflammation should cause outbreaks to be less frequent and less severe. It also may stall or prevent the progression to psoriatic arthritis.

How PDE4 inhibitors work

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 in the Journal of Clinical & Experimental Dermatology Research, this higher rate of cAMP may have anti-inflammatory effects, specifically in people living with psoriasis and atopic dermatitis.

Why PDE4 inhibitor treatments are unique

Biologic treatments such as adalimumab (Humera), etanercept (Enbrel), and infliximab (Remicade) are injected into the body. Apremilast is taken by mouth. It also acts on an important pathway by interrupting the inflammatory response that contributes to the symptoms of plaque psoriasis.

Potential benefits

Apremilast is recommended for people living with moderate to severe plaque psoriasis who are also candidates for systemic therapy or phototherapy. In clinical trials, a greater proportion of people taking apremilast scored well on both the Physicians’ Global Assessment (sPGA) and Psoriasis Area and Severity Index (PASI) compared to those taking a placebo. Participants in the study were allowed to take topical steroids, in addition to the medication or placebo.

Side effects and warnings

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, and headache. Some people also experience significant weight loss.

Apremilast can also increase feelings of depression and suicidal thoughts. People with a history of depression or suicidal behavior should carefully weigh the potential benefits of the drug against the risks. If you do experience side effects, your doctor may recommend stopping the medication.

The takeaway

Psoriasis is a chronic but manageable condition, and the role inflammation plays is the focus of treatment and research. If your doctor feels your plaque psoriasis is mild or well-controlled, they may recommend nonsteroidal anti-inflammatory drugs (NSAIDs) or topical treatments before considering the use of a PDE4 inhibitor.

Researchers have discovered more about the mechanisms in the body that cause inflammation. This has allowed new medications to emerge 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.

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