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There are both intracellular and extracellular targets for treating psoriasis. Therapies that act on intracellular targets work earlier in the inflammatory signaling cascade by impacting the synthesis of inflammatory cytokines. Place the following therapeutic targets inside or outside of the inflammatory cell.
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Inflammatory cell
PDE4 is the only intracellular target shown above. All other targets work outside of the cell.1-3
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PDE4 is an enzyme that controls the intracellular level of cyclic AMP and is expressed in several cell types related to psoriasis. In which cell types below is PDE4 expressed?
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PDE4 is the dominant PDE in inflammatory cells, and it is also expressed in synovial cells and keratinocytes.4
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Based on preclinical data, PDE4, cyclic AMP, and AMP are thought to be involved in the inflammatory response. What is the relationship between PDE4, cyclic AMP, and AMP?
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PDE4 to
PDE4 degrades cyclic AMP into AMP.4
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PDE4 affects levels of cyclic AMP inside a cell, which is thought to subsequently impact activity in the inflammatory signaling cascade. Move the button to the left or right to show what happens when the intracellular cyclic AMP concentration is low.
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Inflammatory Signaling
When intracellular cyclic AMP concentration is low, there is increased inflammatory signaling.4
Otezla (apremilast) is a PDE4 inhibitor. Based on the information in the previous questions, select the up or down arrow under each box to show how Otezla is thought to impact different components in the inflammatory cascade.
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The specific mechanism(s) by which Otezla exerts its therapeutic action is not well defined.

PDE4 Activity
Cyclic AMP
Based on preclinical evidence, Otezla is thought to inhibit the activity of PDE4 (lower activity), which may elevate intracellular cyclic AMP (increased concentrations), and dampen inflammatory signaling (lower inflammatory signaling).2,4-6
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  • Otezla® (apremilast) is indicated for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
  • Otezla is indicated for the treatment of adult patients with active psoriatic arthritis.



  • Otezla® (apremilast) is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation

Warnings and Precautions

  • Diarrhea, Nausea and Vomiting: Cases of severe diarrhea, nausea, and vomiting were associated with the use of Otezla. Most events occurred within the first few weeks of treatment. In some cases patients were hospitalized. Patients 65 years of age or older and patients taking medications that can lead to volume depletion or hypotension may be at a higher risk of complications from severe diarrhea, nausea, or vomiting. Monitor patients who are more susceptible to complications of diarrhea or vomiting; advise patients to contact their healthcare provider. Consider Otezla dose reduction or suspension if patients develop severe diarrhea, nausea, or vomiting
  • Depression: Carefully weigh the risks and benefits of treatment with Otezla for patients with a history of depression and/or suicidal thoughts/behavior, or in patients who develop such symptoms while on Otezla. Patients, caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes, and they should contact their healthcare provider if such changes occur
  • Psoriasis: Treatment with Otezla is associated with an increase in depression. During clinical trials, 1.3% (12/920) of patients reported depression compared to 0.4% (2/506) on placebo; Depression was reported as serious in 0.1% (1/1308) of patients exposed to Otezla, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1% (1/1308) of patients on Otezla, compared to 0.2% (1/506) on placebo. One patient treated with Otezla attempted suicide; one patient on placebo committed suicide
  • Psoriatic Arthritis: Treatment with Otezla is associated with an increase in depression. During clinical trials, 1.0% (10/998) reported depression or depressed mood compared to 0.8% (4/495) treated with placebo. Suicidal ideation and behavior was observed in 0.2% (3/1441) of patients on Otezla, compared to none in placebo treated patients. Depression was reported as serious in 0.2% (3/1441) of patients exposed to Otezla, compared to none in placebo treated patients (0/495). Two patients who received placebo committed suicide compared to none on Otezla
  • Weight Decrease: Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla
  • Psoriasis: Body weight loss of 5-10% occurred in 12% (96/784) of patients treated with Otezla and in 5% (19/382) of patients treated with placebo. Body weight loss of ≥10% occurred in 2% (16/784) of patients treated with Otezla compared to 1% (3/382) of patients treated with placebo
  • Psoriatic Arthritis: Body weight loss of 5-10% was reported in 10% of patients taking Otezla and in 3.3% of patients taking placebo.
  • Drug Interactions: Apremilast exposure was decreased when Otezla was co-administered with rifampin, a strong CYP450 enzyme inducer; loss of Otezla efficacy may occur. Concomitant use of Otezla with CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended

Adverse Reactions

  • Psoriasis: Adverse reactions reported in ≥5% of patients were (Otezla%, placebo%): diarrhea (17, 6), nausea (17, 7), upper respiratory tract infection (9, 6), tension headache (8, 4), and headache (6, 4)
  • Psoriatic Arthritis: Adverse reactions reported in at least 2% of patients taking Otezla, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 16 weeks (after the initial 5-day titration), were (Otezla%, placebo%): diarrhea (7.7, 1.6); nausea (8.9, 3.1); headache (5.9, 2.2); upper respiratory tract infection (3.9, 1.8); vomiting (3.2, 0.4); nasopharyngitis (2.6, 1.6); upper abdominal pain (2.0, 0.2)

Use in Specific Populations

  • Pregnancy and Nursing Mothers: Otezla is Pregnancy Category C; it has not been studied in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether apremilast or its metabolites are present in human milk. Caution should be exercised when Otezla is administered to a nursing woman
  • Renal Impairment: Otezla dosage should be reduced in patients with severe renal impairment (creatinine clearance less than 30 mL/min); for details, see Dosage and Administration, Section 2, in the Full Prescribing Information

For Full Prescribing Information click here.

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