Treating Plaque Psoriasis With PDE4 Inhibitors: Benefits & Side Effects

Plaque psoriasis is a medical condition of the skin where the skin cells start building up and form scales along with itchy and dry patches ⁽¹⁾. Plaque psoriasis is the most common type of psoriasis that affects millions of people around the world ⁽¹⁾. Plaque psoriasis is believed to be an autoimmune condition and its triggers include cold, stress and infections ^{(2, 3)}. The most common symptom of plaque psoriasis is the occurrence of a rash on the skin, but in many cases, this rash can also occur on the nails or the joints ⁽⁴⁾. The patches that develop are known to be very itchy and/or painful. There is no cure for plaque psoriasis and treatment for the condition revolves around management of the symptoms ⁽⁵⁾. Since inflammation is believed to the root cause of plaque psoriasis, most of the medications used for treating plaque psoriasis aim for preventing inflammation. PDE4 inhibitors are known to work from inside the body to prevent inflammation, which happens as an immune system response ⁽⁶⁾. If you suffer from moderate to severe plaque psoriasis, then a PDE4 inhibitor could be the most effective solution for you in managing your symptoms. However, PDE4 inhibitors are not for everyone. Let’s look at the possibility of treating plaque psoriasis with PDE4 inhibitors and what all it involves.

Common referred to only as PDE4 inhibitors, phosphodiesterase type 4 inhibitors, are medications that are used for blocking the degradative action of PDE 4 (phosphodiesterase 4) on cAMP (cyclic adenosine monophosphate), which functions as a messenger in many biological processes in the body ⁽⁷⁾. These PDE4 inhibitors function inside the body to prevent inflammation, which is caused as an immune system response. A common PDE4 inhibitor is apremilast (brand name Otezla) ⁽⁸⁾.

PDE4 inhibitors are a relatively new type of treatment and they work by suppressing the immune system, thus reducing inflammation in the body ⁽⁹⁾. PDE4 inhibitors work at a cellular level and halt the production of the overactive enzyme known as PDE4 in the body. Research over the years has shown that PDEs (phosphodiesterases) degrade the cAMP in the body, which is responsible for contributing to the signaling pathways between the cells. When the PDE4 enzymes are halted, this increases the cAMP.

A 2016 study published in the Journal of Clinical and Experimental Dermatology Research, when there is an increase in cAMP in the body, it gives rise to anti-inflammatory effects, especially in people who are suffering from psoriasis and atopic dermatitis.

The uniqueness of PDE4 inhibitors is that they are injected directly into the body. Biologic treatments include etanercept (brand name Enbrel), adalimumab (brand name Humera), and infliximab (brand name Remicade). Apart from these three, there is apremilast as well, which is taken orally by mouth.

PDE4 inhibitors are known to act upon a crucial pathway in the body by interrupting the inflammatory response that is generated by the immune system and is responsible for the symptoms of plaque psoriasis.

There are many types of psoriasis that affect people, with plaque psoriasis being the most common type ⁽¹⁾. Out of the people who suffer from psoriasis, nearly 30 percent end up developing psoriatic arthritis over a period of time. Psoriatic arthritis causes moderate to severe joint pain, which reduces the quality of your life.

This is why, as a preventive measure, it is recommended that people who have psoriasis, begin to control inflammation from an early stage. Reducing the levels of inflammation in the body also causes a decrease in psoriasis outbreaks and also reduces the severity of symptoms. It is also believed that reducing inflammation prevents or slows down the progression of psoriasis into psoriatic arthritis.

The PDE4 inhibitor apremilast is especially recommended for people who are suffering from mild to severe plaque psoriasis and who are also preferred candidates for phototherapy or systemic therapy ⁽¹⁰⁾.

During clinical trials, it was observed that a greater number of people who were taking apremilast, PDE4 Inhibitors for treating plaque psoriasis ended up scoring better on the Psoriasis Area and Severity Index (PASI) and Physicians’ Global Assessment (sPGA), as compared to people who were taking a placebo. Apart from the medication or placebo, though, the participants of the clinical trial were also taking topical steroids.

While PDE4 inhibitors are showing great promise, these medications are not to be used by everyone. In fact, apremilast is yet to be tested in breastfeeding or pregnant women, and it is only approved for adults at present. Before beginning treatment with PDE4 inhibitors, it is important to consider the benefits and side effects or risks associated with this mode of treatment.

Some of the known side effects of apremilast may include adverse reactions, such as diarrhea, respiratory tract infection, headaches and nausea. Many people have also reported experiencing unintentional weight loss ^{(11, 12 )}. Apremilast has also been known to increase depression and suicidal tendencies in some people ^{(11, 12)}. Due to this, people who have a history of suicidal behavior or depression must carefully consider the potential benefits of PDE4 inhibitors before they begin taking the drug.

If you experience any side effect, then your doctor will recommend you to stop taking the pde4 inhibitors medication or shift you to another medication.

Plaque psoriasis is a chronic autoimmune condition that has no cure, but can be managed with medications and lifestyle changes ⁽⁵⁾. It is important, though, to understand the crucial role inflammation plays in the treatment and progression of psoriasis. If your doctor feels that your plaque psoriasis is well-controlled or mild, then they may recommend that you use topical treatments or nonsteroidal anti-inflammatory drugs (NSAIDs), before moving on to a PDE4 inhibitor.

As researchers discover more about the factors that cause inflammation in the body, new medications are emerging that are providing better and faster relief to people living with plaque psoriasis. PDE4 inhibitors are today one such latest innovation, but they are not without any risks and side effects. Consult with your doctor properly and consider both the pros and cons of taking PDE4 inhibitors, before you begin this new type of treatment for plaque psoriasis.

Referred Links

1. https://www.ncbi.nlm.nih.gov/books/NBK430879/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683130/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995120/
4. https://www.ncbi.nlm.nih.gov/books/NBK279447/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389757/
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695611/
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486098/
8. https://pubchem.ncbi.nlm.nih.gov/compound/Apremilast
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644066/
10. https://www.ncbi.nlm.nih.gov/pubmed/28276777
11. https://livertox.nih.gov/Apremilast.htm
12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110328/

Also Read:

• What is Plaque Psoriasis & How is it Treated?
• Difference between Injectable vs. Oral Plaque Psoriasis Meds
• Do PDE4 Inhibitors Reduce Inflammation in Plaque Psoriasis?