Apremilast- a drug for the treatment of psoriasis

FDA approved Apremilast on September 23, 2014. It was a drug used mainly for the treatment of psoriasis

Common name: Otezla

Mode of administration: oral, each tablet containing 10, 20, or 30 mg of apremilast

What is it used for? Indications of Apremilast

1. Psoriatic arthritis:using apremilast along with Disease-Modifying Antirheumatic Drugs (DMARDs). Inflamed, swollen, and painful joints mark the hallmarks of the disease
2. Psoriasis: one can use Apremilast for moderate to severe psoriasis. It is a chronic disease characterized by an hyperactive immune system causing skin cells to multiply quickly. This results in a scaly and inflamed skin, especially on the scalp
3. Behcet’s disease: one can use Apremilast for the treatment of oral ulcers associated with Behcet’s disease

Contraindications for Apremilast:

1. Hypersensitivity to the active substance 
2. Pregnant and breastfeeding ladies
3. Severe renal impairment: a reduced dosage of apremilast is advisable
4. Underweight patients: a continous monitoring during the treatment is necessary to check for unexplained and clinically significant weight loss

Common side effects:

1. Diarrhea, nausea, and vomiting: seen within the first few weeks of treatment and especially higher in patients above 65 years
2. Decreased appetite
3. Psychiatric disorders: include insomnia and depression

Mechanism of action: 

It acts as a small molecule inhibitor of phosphodiesterase 4 (PDE4), an enzyme responsible for the hydrolysis of cyclic adenosine monophosphate (cAMP). The drug works intracellularly to strengthen the pro-inflammatory and anti-inflammatory mediators. PDE4 is a phosphodiesterase (PDE) specific to cAMP. Upon inhibition of PDE4 by apremilast, cAMP levles increases and thereby decreases the inflammatory response. It does that by modulating the expression of inflammatory cytokines like TNF-alpha, IL-23 and IL-17. These mediators have implications in psoriatic arthritis and psoriasis.

The details of the medication given above is from the spmc of the drug

Let’s look at the latest research relating to this drug:

1. Effect of Apremilast in treating moderate to severe plaque psoriasis: a comparative study over Risanzumab
   Experiment in brief: The study took place in five countries in two phases.
   Phase 1– first 16 days: the patients split into two groups
   118 received Risanzumab (Let’s say drug R)
   234 received Apremilast (Let’s say drug A)
   Result at the end of part 1- Drug showed a better effect by clearing up the skin and improving the quality of life
   Phase 2– after 16 days. The group receiving Drug A in part 1 split into two groups
   One group continued with Drug A and 
   the other group received Drug R
   As expected, Risanzumab showed a better result about clearer skin despite their prior treatment with Drug A. 
   To conclude, the above results indicate Risanzumab as a more effective alternative to Apremilast for the treatment of psoriasis.
2. Apremilast vs Risanzumab for the treatment of moderate chronic psoriasis
   This is similar to the previous study where they compared the effects of Risanzumab and Apremilast on moderate chronic plaque psoriasis. 
   Experiment in brief: a total of 18 patients aged above 18 years were a part of the study
   All of them received 150 mg Risanzumab at week 0 and week 4
   All of them received 30 mg of Apremilast twice daily
   Results: Interpreting of the results was by calculating their PASI scores. A PASI score is a tool that measures how severe and intense the psoriasis is. PASI is short for Psoriasis Area and Severity Index.
   In conclusion, Risanzumab was more efficient than Apremilast
3. Apremilast and Papuloerythroderma of Ofiji (PEO)
   PEO is a skin disorder that causes flat red papules which eventually merge into erythema. This condition results in an elevated serum IgE, lymphopenia, and eosinophilia. They develop a higher risk of gastric cancer. Studies with many drugs like Psoralen+UVA (PUVA), glucocorticoids, etc for the treatment of PEO demonstrated a low clinical efficiency.
   The above work reports an ICSR (individual case safety report) of a man with PEO along with gastric and renal cancer. Upon treatment with Apremilast, he showed improvements in the skin 
4. Apremilast and Refractory Atypical IgA pemphigus
   A recent research work also claims the successful use of apremilast in the treatment of Refractory Atypical IgA pemphigus. It is a rare autoimmune disease that causes painful blisters and eruptions. It is due to high levels of circulating Immunoglobulin A (IgA) against cell surface components like keratinocytes

Overall, even though Risanzumab was a better alternative for the treatment of psoriasis, Apremilast has promising applications in the treatment of diseases like PEO and pemphigus.