What Are PDE Inhibitors? 

PDE inhibitors are medications that block an enzyme in your body called PDE. 

These medicines block four main types of PDE: PDE-3, PDE-4, PDE-5 and non-specific PDE. Each type affects different parts of the body based on how they interact with certain cellular processes. 

For psoriasis, treatment drugs will include PDE-4 inhibitors.

Which PDE Inhibitors Are Used to Treat Psoriasis? 

The FDA has approved two PDE inhibitors for this condition:

A third drug, crisaborole (Eucrisa), has shown in a study that it can help to improve psoriasis. The FDA has only approved this medication to treat eczema, but doctors may prescribe it for psoriasis on an off-label basis.

How Do PDE Inhibitors Work? 

PDE inhibitors block an enzyme called phosphodiesterase (PDE). PDE regulates two cellular messengers: cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). 

By blocking these messengers, PDE inhibitors reduce the inflammatory response in the body. In addition, they relax muscles, widen blood vessels, and make it easier to breathe.

When Are PDE Inhibitors Prescribed for Psoriasis?

Your doctor may prescribe PDE inhibitors when the most common psoriasis therapies don’t give you relief. 

The FDA has approved apremilast for adults whose plaque psoriasis has a negative impact on their quality of life, even if their condition can be classified as mild. 

Roflumilast is approved for the treatment of plaque psoriasis in people aged 12 and older.

How Do You Take PDE Inhibitors? 

PDE inhibitors are easy to take yourself. But there are a few safety precautions to remember:

How long do you take PDE inhibitors?

You’ll need to take apremilast for about 4 months before you start seeing results. 

With roflumilast, you may see your psoriasis improve after 1 month, although most people need  2 months before their psoriasis improves.

PDE Inhibitors infographic

How Effective Are PDE Inhibitors for Psoriasis? 

There are a couple of ways that researchers measure and record how well a psoriasis medication works. 

There are a couple of ways that researchers measure and record how well a psoriasis medication works.

The PASI score measures psoriasis severity and compares it to how severe it was when you start taking a medicine. The sPGA score measures how severe psoriasis is at a given point in time.

Are PDE Inhibitors Safe?

PDE inhibitors tend to be safe for most adults.  

In early clinical studies, some patients displayed worsening depression and an increase in suicidal thoughts while on apremilast. More recent research showed that patients taking the drug didn’t show such symptoms. 

Though PDE inhibitors for psoriasis are generally safe, there are some risks to keep in mind, especially if you’re planning on starting or adding to your family. 

Apremilast

People who take cytochrome P450 enzyme inducers such as carbamazepine, phenobarbital, phenytoin, and rifampin shouldn’t take apremilast as they may interact and be less effective. 

If you’re pregnant or breastfeeding, talk to your doctor before taking apremilast. Animal studies found that the medication could raise the risk of a miscarriage. We need more studies to understand how this drug may affect people. 

Roflumilast

If you’re pregnant, planning to get pregnant, or are breastfeeding, you should talk to your doctor before taking roflumilast. Though there are no studies based on preterm pregnancy and at-term labor, studies in mice found that roflumilast can disrupt the labor and delivery process. 

You might not be able to take roflumilast if you have certain liver problems. Your doctor can let you know if this is the case. 

It’s also not clear how safe roflumilast is for children under the age of 12. People between 12 and 17 taking roflumilast showed side effect results similar to adults.

What Are the Common Side Effects of PDE Inhibitors?

Apremilast

  • Nausea
  • Vomiting
  • Diarrhea
  • Weight loss
  • Headaches (including tension headaches)
  • Upper respiratory tract infections
  • Worsening depression
  • Suicidal thoughts

Roflumilast

  • Diarrhea
  • Headaches
  • Insomnia
  • Upper respiratory tract infections
  • Urinary tract infections
  • Pain at application site

Crisaborole

  • Application site pain 

Managing side effects

Talk to your doctor about managing the side effects of PDE inhibitors for psoriasis.

How Much Do PDE Inhibitors Cost?

PDE inhibitors can be expensive, with the retail list price ranging from several hundred to several thousand dollars per month or drug cycle. But there are ways to reduce the cost of these drugs. 

The first way is to get insurance coverage. Insurance, especially governmental insurance like Medicare and Medicaid, is more likely to cover apremilast or roflumilast prescriptions if you show that more common, cheaper therapies didn’t work for you. 

Insurance is also more likely to cover apremilast if you show a need for systemic psoriasis treatment. For instance, if your psoriasis covers more than 10% of your skin, you would benefit from a medicine that treats your whole body. 

Roflumilast can be used on sensitive areas like the face, groin, underarms, or other sensitive areas. If your psoriasis affects you in these areas, insurance could opt to cover the drug.

Clinical Trials of PDE Inhibitors for Psoriasis

If you take part in a clinical trial for a medication, you help researchers better understand which treatments work best and why. As part of the study, you may get a new medication before it’s available to the public. 

Trials will look at how safe and effective existing PDE inhibitors are compared to both new PDE inhibitors and other types of psoriasis drugs. 

Your doctor may have information about trials that are currently being done that may be a good fit for you. The National Psoriasis Foundation also has a study directory and contact list at its MyStudies page.  

You can also find studies by going to Clinicaltrials.gov. You’ll want to read the details for each study carefully to see what the goal is for the research and whether it’s taking new applications. You’ll also want to note where it’s being done and what criteria you need to meet to qualify.

Learn more about clinical trials. 

Is a PDE Inhibitor for Psoriasis Right for Me? 

As you decide on your treatment for moderate-to-severe plaque psoriasis, you'll want to talk to your doctor and think about these key points:

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Prior Treatments:Your doctor may prescribe PDE inhibitors when you've tried the most common psoriasis therapies first without relief. 

illustration of prescription pill bottle

How You'll Take Your Medicine: These medications are easy to take yourself. You take apremilast as a pill. Roflumilast is a cream you apply to affected areas once a day. If your doctor has prescribed crisaborole off-label for psoriasis, you'll apply the cream twice a day on affected areas. 

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Potential Side Effects: The side effects of PDE inhibitors can be mild or more serious. The most common are nausea, vomiting, diarrhea and headaches. More serious ones include upper respiratory and urinary tract infections (UTIs). In some cases, apremilast may cause suicidal thoughts. Talk to your doctor right away about any side effects you have while taking PDE inhibitors. 

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Costs: PDE inhibitors can cost several hundred to several thousand dollars per month or drug cycle. But insurance can help, especially governmental insurance like Medicare and Medicaid. Your insurer is more likely to cover prescriptions when other less expensive therapies didn’t work for you. You also have a better chance of getting coverage if you need for systemic treatment or if your psoriasis affects sensitive areas. Copay cards or assistance programs from the makers of these medications could help you pay nothing for drug treatments each month. 

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Medical History and Related Conditions:If you’re pregnant, planning to get pregnant, or breastfeeding, talk to your doctor before taking a PDE inhibitor. It's not yet completely understood how this drug may affect the developing baby. 

It’s also not clear how safe roflumilast is for children under the age of 12. 

People who take cytochrome P450 enzyme inducers such as carbamazepine, phenobarbital, phenytoin, and rifampin shouldn’t take apremilast as they may interact with it and be less effective.

Show Sources

SOURCES:  

National Institute of Arthritis and Musculoskeletal and Skin Diseases: “Psoriasis.”

National Library of Medicine: “Phosphodiesterase Inhibitors.”

Medscape: “New Data Forecast More Oral PDE4 Inhibitors for Psoriasis.”

Current Opinion in Pharmacology: “Phosphodiesterase function and endocrine cells: links to human disease and roles in tumor development and treatment.”

Dermatologic Therapy: “Phosphodiesterase 4 Inhibition in the Treatment of Psoriasis, Psoriatic Arthritis and Other Chronic Inflammatory Diseases.”

Paras Vakharia, MD, assistant professor of dermatology, Northwestern Medicine.

National Health Service: “Steroids.”

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Zoryve.com: “Zoryve: Roflumilast.” 

Journal of the American Academy of Dermatology: “Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1),” “Long-term safety and effectiveness of roflumilast cream 0.3% in adults with chronic plaque psoriasis: A 52-week, phase 2, open-label trial,” ”Decision points for the initiation of systemic treatment for psoriasis,” “Crisaborole 2% ointment for the treatment of intertriginous, anogenital, and facial psoriasis: A double-blind, randomized, vehicle-controlled trial,” “Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial.”

Otezla.com: “Otezla (Apremilast).” 

Canadian Journal of Health Technologies: “Roflumilast (Zoryve).”

MedlinePlus: “Apremilast.”

National Psoriasis Foundation: “FDA Approves First Oral Treatment for All Psoriasis Severities.”

ClinicalTrials.gov.

DermNet: “PASI Score.” 

Australasian Journal of Dermatology: “Mental health, insomnia and suicidal ideation during treatment with apremilast.”

Pediatric Drugs: “Topical Management of Pediatric Psoriasis: A Review of New Developments and Existing Therapies.” 

DermNet: “Key clinical-trial evidence for crisaborole.” 

Psoriasis and Psoriatic Arthritis Alliance: “Psoriasis and Lung Disease.”