3 INDICATIONS

3 INDICATIONS Otezla® (apremilast) is indicated for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. Read more

Otezla is indicated for the treatment of adult patients with active psoriatic arthritis.

Otezla is indicated for the treatment of adult patients with oral ulcers associated with Behçet's Disease. Read less

Otezla® (apremilast) Mechanism of Action (MOA)

Otezla is an oral, systemic, PDE4 inhibitor with a distinct MOA that works intracellularly and has anti-inflammatory properties1,2

Dial down inflammatory drivers with Otezla2

Visual representation of the mechanism of action of Otezla that elevates cAMP levels and believed to indirectly modulate production of inflammatory mediators

*Increase based on the PALACE 1 biomarker substudy. Decrease based on the PALACE 1 and ESTEEM 2 biomarker substudies. Visual representation based on preclinical evidence.

  • The specific mechanism(s) by which apremilast exerts its therapeutic action is not well defined1
  • Phosphodiesterase 4 (PDE4) and cyclic adenosine monophosphate (cAMP) play a role in controlling inflammation3
    • PDE4 has been shown to degrade cAMP to AMP in inflammatory cells, which may modulate the expression of pro-inflammatory and anti-inflammatory mediators2,4

These biomarker analyses were exploratory and not designed to detect changes in biomarker levels or the relationship between biomarker change and clinical outcome5

  • An exploratory PALACE 1 substudy evaluating 47 biomarkers, some of which are relevant in the pathophysiology of psoriatic disease, observed an increase in anti-inflammatory mediators such as IL-10 and a decrease in pro-inflammatory mediators such as TNF-α, IL-12, IL-17A, and IL-234,6,§,**
  • An exploratory ESTEEM 2 biomarker substudy evaluating 47 biomarkers, some of which are relevant in the pathophysiology of psoriasis, observed a decrease in pro-inflammatory mediators such as IL-17F, IL-17A, IL-22, and TNF-α7,††

§Based on an exploratory PALACE 1 biomarker substudy of patients with active psoriatic arthritis (n=150 peripheral blood plasma samples at baseline and at weeks 4, 16, 24, and 40) for a total of 47 biomarkers using a validated multiplexed immunoassay. **Prior exposure to a biologic was higher in the biomarker subset compared to the full patient population (49% vs 24%). ††Based on an ESTEEM 2 substudy (placebo, n=47; Otezla, n=83; peripheral blood plasma samples collected at baseline and at weeks 4, 16, 32, 36, 40, and 44) using a validated multiplex immunoassay. High-sensitivity assays were used to measure IL-17F, IL-17A, IL-22, and TNF-α.

Otezla MOA Videos

Otezla inhibits PDE4 intracellularly and has anti-inflammatory properties1,2

Mechanism of action in plaque psoriasis

See how Otezla may work in moderate to severe plaque psoriasis

The specific mechanism(s) by which apremilast exerts its therapeutic action in patients with psoriasis is not well defined.1

Video transcript

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Mechanism of Action in Plaque Psoriasis

INDICATION

Otezla® (apremilast) is indicated for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

IMPORTANT SAFETY INFORMATION

Contraindications

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

Please see additional Safety Information later in this video.

Plaque psoriasis appears on the skin as raised, red patches covered with a silvery buildup of dead skin cells. Plaque psoriasis most commonly appears on the knees, fingernails, elbows, lower back, and scalp. Data from cell and animal studies indicates that the immune cell releases pro-inflammatory cytokines that can then activate other cells. The activated cells recruit more cells to the site of the disease creating a chronic cycle of inflammation. Recent research has identified important signaling molecules within immune cells. One such molecule is phosphodiesterase 4 or PDE4, an intracellular enzyme that degrades cyclic AMP into its inactive form, AMP in inflammatory cells. A treatment for plaque psoriasis, apremilast, an inhibitor of PDE4 is indicated for the treatment of adult patients with moderate to severe plaque psoriasis. Apremilast is an oral small-molecule inhibitor of PDE4. The specific mechanisms by which apremilast exerts its therapeutic action is not well defined. Through this targeted inhibition, apremilast elevates intracellular cAMP levels, which is thought to decrease levels of some pro-inflammatory mediators and increase the production of certain anti-inflammatory mediators.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Diarrhea, Nausea, and Vomiting: Cases of severe diarrhea, nausea, and vomiting have been reported 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: 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. Suicidal behavior was observed in 0.1% (1/1308) of patients on Otezla, compared to 0.2% (1/506) on placebo. 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.

Weight Decrease: 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. Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla.

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

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).

Use in Specific Populations

Pregnancy: Otezla has not been studied in pregnant women. Advise pregnant women of the potential risk of fetal loss. Consider pregnancy planning and prevention for females of reproductive potential. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Otezla during pregnancy. Information about the registry can be obtained by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing study/otezla/.

Lactation: There are no data on the presence of apremilast or its metabolites in human milk, the effects of apremilast on the breastfed infant, or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Otezla and any potential adverse effects on the breastfed child from Otezla or from the underlying maternal condition.

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.

Please see full Prescribing Information at OtezlaPro.com

Mechanism of action in psoriatic arthritis

See how Otezla may work in
psoriatic arthritis

The specific mechanism(s) by which apremilast exerts its therapeutic action in patients with psoriatic arthritis is not well defined.1

Video transcript

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Otezla is an Oral Treatment Option for Psoriatic Arthritis Patients

INDICATION

Otezla is indicated for the treatment of adult patients with active psoriatic arthritis. Important Safety Information, contraindications: Otezla is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation. Please see additional Important Safety Information later in this video. Psoriatic arthritis is an inflammatory disease which develops in up to 30 percent of people that experience psoriasis.

Psoriatic arthritis typically affects the peripheral and distal joints of the fingers and toes, but can sometimes affect the spine and sacroiliac area. Data from cell and animal studies indicates that the immune cell releases pro-inflammatory cytokines that can then activate other cells. The activated cells recruit more cells to the side of the disease, creating a chronic cycle of inflammation. Recent research has identified important signaling molecules within immune cells. One such molecule is phosphodiesterase 4 or PDE4, an intracellular enzyme that degrades cyclic AMP into its inactive form AMPE and inflammatory cells. A treatment for psoriatic arthritis apremilast, an inhibitor of PDE4 is indicated for the treatment of adult patients with active psoriatic arthritis. Apremilast is an oral small molecule inhibitor of PDE4. The specific mechanisms by which apremilast exerts its therapeutic action in psoriatic arthritis patients is not well defined. Through this targeted inhibition, apremilast, elevates intercellular CAMP levels, which is thought to decrease levels of some pro-inflammatory mediators and increase the production of certain anti-inflammatory mediators.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Diarrhea, Nausea, and Vomiting: Cases of severe diarrhea, nausea, and vomiting have been reported 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: 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. Suicidal behavior was observed in 0.1% (1/1308) of patients on Otezla, compared to 0.2% (1/506) on placebo. 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.

Weight Decrease: 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. Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla.

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

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); nasal pharyngitis (2.6, 1.6); upper abdominal pain (2.0, 0.2).

Use in Specific Populations

Pregnancy: Otezla has not been studied in pregnant women. Advise pregnant women of the potential risk of fetal loss. Consider pregnancy planning and prevention for females of reproductive potential. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Otezla during pregnancy. Information about the registry can be obtained by calling 1.877.311.8972 or by visiting https://www.mothertobaby.org/ongoing-study/Otezla/.

Lactation: There are no data on the presence of apremilast or its metabolites in human milk, the effects of apremilast on the breastfed infant, or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Otezla and any potential adverse effects on the breastfed child from Otezla or from the underlying maternal condition.

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.

Please see full Prescribing Information at OtezlaPro.com

ESTEEM, Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis; IL, interleukin; PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy; TNF, tumor necrosis factor.

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IMPORTANT SAFETY INFORMATION

Contraindications

  • 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
    • Behçet’s Disease: Treatment with Otezla is associated with an increase in depression. During the clinical trial, 1% (1/104) reported depression or depressed mood compared to 1% (1/103) treated with placebo. No instances of suicidal ideation or behavior were reported in patients treated with Otezla or treated with placebo
  • 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% (49/497) of patients taking Otezla and in 3.3% (16/495) of patients taking placebo
    • Behçet’s Disease: Body weight loss of >5% was reported in 4.9% (5/103) of patients taking Otezla and in 3.9% (4/102) 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)
  • Behçet’s Disease: Adverse reactions reported in ≥5% of patients taking Otezla, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 12 weeks, were (Otezla%, placebo%): diarrhea (41.3, 20.4); nausea (19.2, 10.7); headache (14.4, 10.7); upper respiratory tract infection (11.5, 4.9); upper abdominal pain (8.7, 1.9); vomiting (8.7, 1.9); back pain (7.7, 5.8); viral upper respiratory tract infection (6.7, 4.9); arthralgia (5.8, 2.9)

Use in Specific Populations

  • Pregnancy: Otezla has not been studied in pregnant women. Advise pregnant women of the potential risk of fetal loss. Consider pregnancy planning and prevention for females of reproductive potential. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Otezla during pregnancy. Information about the registry can be obtained by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/otezla/
  • Lactation: There are no data on the presence of apremilast or its metabolites in human milk, the effects of apremilast on the breastfed infant, or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Otezla and any potential adverse effects on the breastfed child from Otezla or from the underlying maternal condition
  • 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

Please click here for Full Prescribing Information.

INDICATIONS

Otezla® (apremilast) is indicated for the treatment of adult 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 is indicated for the treatment of adult patients with oral ulcers associated with Behçet’s Disease.

References: 1. Otezla [package insert]. Thousand Oaks, CA: Amgen Inc. 2. Schafer PH, Parton A, Capone L, et al. Cell Signal. 2014;26(9):2016-2029. 3. Schafer PH, Parton A, Gandhi AK, et al. Br J Pharmacol. 2010;159(4):842-855.4. Schafer P. Biochem Pharmacol. 2012;83(12):1583-1590. 5. Data on file, Amgen Inc. 6. Schafer PH, Chen P, Fang L, Wang A, Chopra R. J Immunol Res. 2015;2015:906349. 7. Garcet S, Nograles K, Correa da Rosa J, Schafer PH, Krueger JG. J Allergy Clin Immunol. 2018;142(3):1010-1013.