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PDE4 Inhibitors and Psoriasis: How Do They Affect You?

Posted on November 11, 2021
Medically reviewed by
Ariel D. Teitel, M.D., M.B.A.
Article written by
Candace Crowley, Ph.D.

Many effective psoriasis treatments exist today, including medications that are applied to the skin, taken by mouth, or injected. Phosphodiesterase 4 (PDE4) inhibitors are prescription pills that fight chronic inflammation and improve the quality of life for people with psoriasis.

There are several types of PDE4 inhibitors for health conditions related to excess inflammation: Otezla (apremilast) is a PDE4 inhibitor that treats psoriasis and psoriatic arthritis. Eucrisa (crisaborole) is a PDE4 inhibitor approved to treat atopic dermatitis (eczema) and is sometimes used off-label to treat psoriasis.

People living with psoriasis may wonder how PDE4 inhibitors work and whether this type of drug is a good treatment option for them.

What Are PDE4 Inhibitors?

PDE4 is a natural enzyme produced by several of the body’s cell types, including immune and skin cells. PDE4 helps regulate inflammation by breaking down another chemical called cyclic adenosine monophosphate (cyclic amp or cAMP). When PDE4 breaks down cAMP, it triggers the immune system to produce compounds called cytokines, which stimulate inflammatory responses in the body. These cytokines include tumor necrosis factor-alpha, interleukin 17, and interleukin 23. People with certain inflammatory conditions are often found to have a genetic cause for higher-than-normal levels of PDE4.

PDE4 inhibitors work by stopping PDE4 from breaking down cAMP. Several PDE4 inhibitors have been approved by the U.S. Food and Drug Administration (FDA) for treating inflammatory diseases. For example, roflumilast is used to treat chronic obstructive pulmonary disease and inflammatory airway diseases such as asthma.

PDE4 Inhibitors and Psoriasis

In psoriasis, the immune system is activated too much and inappropriately. Abnormally high amounts of inflammatory chemicals are produced by the body’s immune cells, like the aforementioned cytokines. These chemicals stimulate the formation of the thick, itchy skin plaques seen in psoriasis. PDE4 inhibitor medications not only block the production of these inflammatory cytokines; they also can stimulate anti-inflammatory cytokines, easing chronic inflammation and psoriasis symptoms.

The FDA approved the PDE4 inhibitor Otezla (apremilast) in 2014 to treat adults with active psoriatic arthritis and moderate to severe plaque psoriasis. Currently, it’s the only PDE4 drug approved for treating psoriasis, though doctors will sometimes prescribe Eucarisa, approved for eczema, to people with psoriasis. Apremilast is safe and effective for the treatment of psoriatic arthritis and plaque psoriasis.

Clinical studies show that apremilast improves joint swelling, pain, and physical function compared to placebo. In addition, apremilast lowers disease severity markers in the blood, such as C-reactive protein. In plaque psoriasis, apremilast has been shown to decrease the size, scaling, thickness, and erythema (discoloration) of skin plaques. Clinical trials also show apremilast improves nail and scalp psoriasis symptoms.

PDE4 inhibitors such as apremilast are prescribed for the treatment of psoriasis in individuals who don’t respond to topical treatments or who cannot take other drugs such as the biologics Enbrel (etanercept) and Humira (adalimumab). Apremilast is also used in individuals who are unable to take other types of medications due to prolonged treatment with corticosteroids or underlying medical conditions such as cancer, HIV, heart failure, liver disease, or nervous system disease.

What Can You Expect When Taking PDE4 Inhibitors?

Apremilast is available as a 30-milligram pill that is taken orally (swallowed). Apremilast pills should be swallowed whole without crushing, chewing, or splitting. Apremilast is usually taken twice a day, 12 hours apart. In some cases, dermatologists recommend slowly increasing the drug dose for the first seven days to reduce potential gastrointestinal side effects. Apremilast pills can be taken with or without food and can be used alongside other psoriasis treatments such as phototherapy.

Side Effects

PDE4 inhibitors like apremilast are generally safe. They are associated with some side effects, but these are usually mild. According to the American Academy of Dermatology Association, common side effects of apremilast include:

  • Headache
  • Diarrhea
  • Nausea and vomiting
  • Upper respiratory tract infections
  • Runny nose and sneezing

In rare cases, apremilast can cause severe side effects such as mood changes, depression, or suicidal thoughts. Anyone considering PDE4 inhibitors like apremilast should discuss their history of depression with their dermatologist. In addition, people with kidney disease or people who are pregnant, breastfeeding, or planning to become pregnant should discuss potential side effects with their dermatologist before taking apremilast.

Drug Interactions

Apremilast can interact with other drugs, so individuals need to discuss all of their medications with their health care team. Due to the potential for side effects, apremilast should not be used with certain drugs that increase levels of liver enzymes, such as rifampin and carbamazepine.

Talk With Others Who Understand

MyPsoriasisTeam is the social network for people with psoriasis and their loved ones. On MyPsoriasisTeam, more than 99,000 members come together to ask questions, give advice, and share their stories with others who understand life with psoriasis.

Do you take PDE4 inhibitors, or are you considering starting treatment? Share your experience in the comments below, or start a conversation by posting on your Activities page.

All updates must be accompanied by text or a picture.
Ariel D. Teitel, M.D., M.B.A. is the clinical associate professor of medicine at the NYU Langone Medical Center in New York. Review provided by VeriMed Healthcare Network. Learn more about him here.
Candace Crowley, Ph.D. received her doctorate in immunology from the University of California, Davis, where her thesis focused on immune modulation in childhood asthma. Learn more about her here.

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