How Do PDE4 Inhibitors (DMARDs) Work?

Phosphodiesterase-4 (PDE4) inhibitors belong to a class of medications known as disease-modifying anti-rheumatic drugs (DMARDs). PDE4 inhibitors are prescribed to reduce inflammation and slow down disease progression in psoriasis, an inflammatory skin condition that can also lead to joint inflammation in many patients.

PDE4 inhibitors restore intracellular stability (homeostasis) of pro-inflammatory and anti-inflammatory signals by inhibiting the activity of PDE4. Phosphodiesterase-4 is an enzyme that breaks down signaling molecules known as cyclic adenosine monophosphate (cAMP), which modulate immune responses.

Inhibition of PDE4 leads to an increase in the intracellular concentration of cAMP, which suppresses the release of pro-inflammatory proteins such as tumor necrosis factor-alpha (TNF-A) and interleukin-23 (IL-23) and increases the release of anti-inflammatory protein IL-10, restoring homeostasis in inflammation signaling.

PDE4 inhibitors (DMARDs) are oral tablets used in the treatment of the following conditions:

FDA-approved:

• Psoriasis
• Psoriatic arthritis
• Oral ulcers associated with Behcet’s disease, a rare disorder that causes inflammation of blood vessels

Orphan designation:

• Pediatric ulcerative colitis

Side effects of PDE4 inhibitors (DMARDs) may include the following:

• Diarrhea
• Nausea
• Upper abdominal pain
• Vomiting
• Headache
• Back pain
• Upper respiratory tract infection
• Viral upper respiratory tract infection
• Arthralgia (joint pain)
• Tension headache
• Fatigue
• Dyspepsia (indigestion)
• Gastroesophageal reflux disease (GERD)
• Decreased appetite
• Weight loss
• Frequent bowel movements
• Insomnia
• Migraine
• Depression
• Bronchitis (inflammation of the bronchial passage)
• Cough
• Tooth abscess
• Folliculitis (inflammation of hair follicles)
• Hypersensitivity reactions such as rash

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of the FDA-approved PDE4 inhibitor (DMARD) are:

• apremilast
• Otezla