*Estimates of patients treated reflect global data since launch (Apr 2014-Aug 2022; US=approximately 60% of
data). Calculations based on observed drug utilization
parameters and number of units distributed. Utilization patterns change over time to best represent current
FDA, U.S. Food and Drug Administration; PsA, psoriatic arthritis; TB, tuberculosis.
References: 1. Otezla [package insert]. Thousand Oaks, CA: Amgen Inc. 2. Data
on file, Amgen Inc. 3. Otezla® (apremilast) FDA approval letter. March 21, 2014.
LIBERATE STUDY DESIGN
LIBERATE was a global, Phase 3b, placebo-controlled, double-blind, double-dummy study evaluating 250 patients with moderate to severe plaque psoriasis for up to 104 weeks 1
Study Design 1
*Starting at week 32, all nonresponders (<PASI-50) had the option of adding topical therapies and/or ultraviolet light B phototherapy to their treatment regimen. †Screening up to 35 days before randomization. ‡For patients randomized to apremilast, doses were titrated over the first week of treatment. §At week 16, all placebo and biologic control arm patients were switched to open-label apremilast 30 mg BID through week 104.
Patients were randomized 1:1:1 to either Otezla 30 mg (n=83) BID, biologic control arm (n=83) once weekly, or placebo (n=84) through week 16. At week 16, all patients crossed over to the Otezla arm 1
This study was not designed for apremilast vs biologic control arm comparisons 1
Criteria and endpoints
Selected inclusion criteria 1:
Chronic moderate or severe plaque psoriasis for ≥12 months
PASI score ≥12
BSA involvement ≥10%
sPGA score ≥3 (moderate to severe)
Inadequate response, intolerance, or contraindication to ≥1 conventional systemic agent for treatment of plaque psoriasis
Candidates for phototherapy or systemic therapy
No prior exposure to a biologic therapy for plaque psoriasis or psoriatic arthritis
Selected exclusion criteria 1:
Prior failure of >3 systemic agents for treatment of plaque psoriasis
History of known demyelinating diseases such as multiple sclerosis or optic neuritis or history of/or concurrent congestive heart failure, including medically controlled, asymptomatic, congestive heart failure
Other clinically significant or major uncontrolled disease
Latent, active, or history of incompletely treated TB
Primary endpoint 1:
Proportion of patients treated with apremilast or placebo who achieved PASI-75 at week 16
Mean age 1:
Otezla, 46 years; placebo, 43 years; biologic control arm, 47 years
Mean baseline BSA involvement 1:
Otezla, 27%; placebo, 27%; biologic control arm, 28%
Mean baseline PASI score 1:
Otezla, 19.3; placebo, 19.4; biologic control arm, 20.3
Otezla is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation
Warnings and Precautions
Hypersensitivity: Hypersensitivity reactions, including angioedema and anaphylaxis, have been reported during postmarketing surveillance. If signs or symptoms of serious hypersensitivity reactions occur, discontinue Otezla and institute appropriate therapy
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
Plaque Psoriasis: Treatment with Otezla is associated with an increase in depression. During clinical trials in patients with moderate to severe plaque psoriasis, 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
Plaque Psoriasis: Body weight loss of 5-10% occurred in 12% (96/784) of patients with moderate to severe plaque psoriasis 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
Plaque Psoriasis: The most common adverse reactions (≥5%) are diarrhea, nausea, upper respiratory tract infection, and headache, including tension headache. Overall, the safety profile of Otezla
in patients with mild to moderate plaque psoriasis was consistent with the safety profile previously established in adult patients with moderate to severe plaque psoriasis
Psoriatic Arthritis: The most common adverse reactions (≥5%) are diarrhea, nausea, and headache
Behçet’s Disease: The most common adverse reactions (≥10%) are diarrhea, nausea, headache, and upper respiratory tract infection
Use in Specific Populations
Otezla has not been studied in pregnant women. Advise pregnant women of the potential risk of fetal loss
Please click here for the full Prescribing Information.
Otezla® (apremilast) is indicated for the treatment of adult patients with 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.
Reference: 1. Reich K, Gooderham M, Green L, et al. J Eur Acad Dermatol Venereol. 2017;31(3):507-517.