Otezla is a drug created by Celgene Corporation to treat moderate to severe plaque psoriasis and psoriatic arthritis. It works by inhibiting the phosphodiesterase 4 enzyme, which reduces inflammation. Clinical studies showed patients experienced a reduction in symptoms and improvement in their conditions. Common side effects include diarrhea, nausea, and headache. Otezla provides an oral treatment option for these autoimmune disorders.

1. Otezla
Group members:
Bilal Tahir
Chan Le Roy
Dikshita Ramkhalawon
Siau Yaw Wen
Rachel Cheong Pui Yi

2. Introduction:
● Otezla (Apremilast) was created by a drug company name Celgene Corporation
● Each tablet costs about $32.94 per unit for 27 tablets and $62.47 per unit for 55 tablets,
having a price of $889.38 and $3436.05 respectively
● A type of small molecule inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4)
● Used to treat moderate to severe plaque psoriasis and active psoriatic arthritis
● Psoriasis is a type of autoimmune or inflammatory disease that caused raised, red, scaly
patches to appear on the skin while psoriatic arthritis is an inflammatory disease of the
joints

3. Description and Taxonomy:
● Otezla is available orally and is not an injection, cream or biologics.
● Chemically identified as N-[2-[(1S)-1-(3-ethoxy-4-
methoxyphenyl)- 2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-
1H-isoindol-4-yl] acetamide.
● Molecular formula and weight are C22H24N2O7S and 460.5 g/mole,
respectively.
● Apremilast belongs to a class of organic compounds known as
phthalimides. These are aromatic heterocyclic compounds
containing a 1,3-dioxoisoindoline moiety and are imide derivatives
of phthalic anhydrides.

4. Discussion :
Mechanism:
Inflammatory cell in psoriasis Apremilast as inhibitor in inflammatory cell.
❖ Phosphodiesterase (PDE4) is cAMP-specific PDE and degrades cytoplasmic cAMP to AMP in inflammatory cells.
❖ cAMP is a second messenger for a variety of inflammatory mediators.
❖ Balance between cAMP and AMP within a cell may modulate the expression of pro-inflammatory and anti-inflammatory
cells.
❖ Studies involving evaluation of biomarkers responsible for inflammation within the cell relevant to pathophysiology of
psoriatic arthritis revealed:
a) Increase in anti-inflammatory mediators such as IL-10 is observed
b) Decrease in pro-inflammatory mediators such as TNF-alpha, IL-17A and IL-23.
(Celgene Corporation, n.d.) (Celgene Corporation, n.d.)

5. Clinical Studies :
Randomised, Double
blinded study for evaluation
PALACE-3
(Plaque psoriasis )
PALACE-1
( Psoriatic arthritis
)
PALACE-2
( Psoriatic arthritis)
★ Total of 1493 adult suffering from active psoriatic arthritis participated in studies for evaluation of therapeutic effects of
apremilast.
★ Classification Criteria for Psoriatic Arthritis [CASPAR] with 3 or more swollen joints and 3 or more tender joints was used.
★ Prior to this therapy 76% had non biologic disease modifying antirheumatic drugs (DMARDS) while 22% patients had
biologics DMARDS treatment. Starting dosage of 10 mg was used and later increased to 20 mg or 30 mg for different group.
★ After 5 year prolonged studies promising results were obtained and the condition was assessed using 3 criteria such as
patient pain assessment, physician or physician global assessment etc.
★ Patients responded with ACR 20 response (meaning 20% improvement in overall condition) by week 16. And even ACR 50
or 70 response was recorded with 20 mg or 30 mg dose daily twice.

6. Benefits:
● It exists as a tablet and available orally
● Able to achieve 75% clearer skin after just 4 months with reduced redness, thickness
and scaliness of plaques
● Works inside the body as it reduce inflammation
● No requirement for initial or routine blood testing
● Otezla is specifically tested and FDA approved

7. Precautions:
❖ Depression and suicide
➢ Otezla can increase depression and suicidal behaviour in patients.
❖ Weight loss
➢ It has been reported that some patients had weight decreased after consumed
Otezla.
❖ Some medicines may make Otezla less effective, and should not be taken with Otezla.
❖ May develop to psoriatic arthritis. Psoriatic arthritis can cause
➢ Pain
➢ Stiffness
➢ Swelling in and around the joint

8. Side Effects:
More common
● Body aches/pains
● Chills
● Cough
● Diarrhoea
● Ear congestion
● Headache
● Loss of voice
● Nausea
● Sneezing
● Sore throat
● Nasal congestion
Less Common
● Back pain
● Belching
● Pain in the hairy areas, pus at the roots of the
hair
● Decreased appetite
● Heartburn
● Indigestion
● Muscle aches
● Stomach discomfort
● Vomiting

9. Plaque Psoriasis and Psoriatic Arthritis:
● Psoriasis is a type of autoimmune or inflammatory disease that caused raised, red, scaly patches
to appear on the skin. Psoriasis manifests into plaque psoriasis which is a chronic, relapsing,
inflammatory skin disorder with a strong genetic basis. Often intractable to treatment.
● Psoriatic arthritis is an inflammatory disease of the joints.
● Psoriasis is when the skin cells grow at an abnormally fast rate, causing the buildup of psoriasis
lesions.
● It usually affects the outside of the elbows, knees or scalp, though it can appear on any location.
● Psoriatic arthritis affects any joint of the body but more often on hands, feet, knees, neck, spine
and elbows. Condition can range from mild to severe.

10. Plaque Psoriasis
Psoriatic Arthritis

11. Conclusion:
➔ Otezla is a product of an American biotech company Celgene which discovers,
develops and commercializes medicine for inflammatory disorders and cancer.
➔ Otezla is proven to be useful to treat moderate to severe psoriatic arthritis and plaque
psoriasis.
➔ Apremilast is the active ingredient which is classified as small molecule inhibitor.
➔ Mechanism relies on inhibiting the inflammatory response of intracellular PDE4
➔ Promising results were obtained in overall improvement in condition during clinical
studies.
➔ As with any drug certain precautions are also stated to the patients.

12. References:
1. Celgene Corporation n.d., Mechanism of action diagram - Otezla, viewed 16 November 2018,
<https://www.otezlapro.com/psoriatic-arthritis/mechanism-of-action/#>.
2. Celgene Corporation n.d., Mechanism of action diagram - PDE4, viewed 16 November 2018,
<https://www.otezlapro.com/psoriatic-arthritis/mechanism-of-action/#>.
3. DrugBank 2018, Apremilast, viewed 14 November 2018, <https://www.drugbank.ca/drugs/DB05676>.
4. Drugs.com 2018, Apremilast side effects, viewed 18 November 2018,
<https://www.drugs.com/sfx/apremilast-side-effects.html>.
5. Drugs.com 2018., Otezla, viewed 14 November 2018, <https://www.drugs.com/otezla.html>.
6. Drugs.com n.d., Otezla prices, coupons and patient assistance programs, viewed 14 November 2018,
<https://www.drugs.com/price-guide/otezla>.