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Psoriatic Arthritis

Efficacy

Results from Otezla® (apremilast) clinical trials
 
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Selected 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 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

Selected Safety Information

Warnings and Precautions (cont’d)

  • Depression: 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 (0/495). 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

Selected Safety Information

Warnings and Precautions (cont'd)

  • Weight Decrease: Body weight loss of 5-10% was reported in 10% of patients taking Otezla and in 3.3% of patients taking placebo. Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla

Selected Safety Information

Warnings and Precautions (cont'd)

  • 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

Selected Safety Information

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); nasopharyngitis (2.6, 1.6); upper abdominal pain (2.0, 0.2)

Selected Safety Information

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

Selected Safety Information

Use in Specific Populations (cont'd)

  • 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

Selected 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 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

Selected Safety Information

Warnings and Precautions (cont'd)

  • Depression: 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 (0/495). 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

OTEZLA SIGNIFICANTLY IMPROVED ACR20 RESPONSE, WITH OR WITHOUT DMARDs1-3

ACR20 responders at week 16 (primary endpoint) in PALACE™ 11-3

Nonresponder imputation; full analysis set

 
  • Otezla also significantly improved ACR20 response vs placebo at week 16 in PALACE 2 and 3; nonresponder imputation intent-to-treat analysis1,2,4,5
  • ACR responses observed in the groups treated with Otezla were consistent in patients who had received either prior small-molecule or prior biologic DMARD use2
 

ACR, American College of Rheumatology; DMARD, disease-modifying antirheumatic drug; PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

ACR20 RESPONSE THROUGH WEEK 2082,3

ACR20 responders in PALACE 12,3,a

Secondary endpoint; data as observed

 
 

Includes all patients exposed to Otezla from baseline who completed treatment through week 208.

a

Data are presented "as observed" with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 208 weeks.

b

n/N, number of responders/number of subjects who had sufficient data for a definitive determination of response status at the time point, which includes subjects who discontinued early between the preceding time point and the specific time point.

  • Patients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other)3
  • Placebo-controlled efficacy data were collected and analyzed through week 24. Placebo nonresponders at week 16 were re-randomized to either 20 mg twice daily or 30 mg twice daily Otezla. At week 24, all remaining patients receiving placebo were re-randomized to either 20 mg twice daily or 30 mg twice daily. Patients treated with Otezla remained on their initial treatment. Patients entering a long-term extension phase could be treated through 5 years1-3
 

Selected 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 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
Next: Joint Tenderness and Swelling

Mean reduction in joint tenderness and swelling through week 2082,3

Mean percent reduction in tender and swollen joints in PALACE 12,3,a,b

Prespecified analysis; data as observed

 

 Includes all patients exposed to Otezla from baseline who completed treatment through week 208.

a

Data are presented "as observed" with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 208 weeks.

b

Patients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other).

c

The n at each time point represents patients with a baseline value and a post-baseline value at the time point and includes subjects who discontinued early between the preceding time point and the specific time point.

 

PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

Treatment with Otezla also significantly improved all other measured ACR components vs placebo at week 16—pain and global disease activity assessed by patients, global disease activity assessed by physicians, Health Assessment Questionnaire–Disability Index (‍H‍A‍Q‍–‍D‍I‍)‍, and CRP (C-reactive protein)1,2*

*

Data based on results of an LOCF analysis of the FAS population.

 

ACR, American College of Rheumatology; FAS, full analysis set; LOCF, last observation carried forward.

Selected Safety Information

Warnings and Precautions

  • Depression: 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 (0/495). 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
Next: Dactylitis

RESOLUTION OF PREEXISTING DACTYLITIS THROUGH WEEK 2082

Patients achieving resolution of preexisting dactylitis in PALACE 1-32,a-c

Secondary endpoint; data as observed

 

Includes all patients exposed to Otezla from baseline who completed treatment through week 208.

a

Dactylitis Severity Score of 0 indicates that all digits in the hands and feet are free of dactylitis.

b

Data are presented "as observed" with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 208 weeks.

c

Patients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other).

d

n/N, number of responders/number of subjects who had sufficient data for a definitive determination of response status at the time point, which includes subjects who discontinued early between the preceding time point and the specific time point.

 

PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

 

 

 

Selected Safety Information

Warnings and Precautions

  • Weight Decrease: Body weight loss of 5-10% was reported in 10% of patients taking Otezla and in 3.3% of patients taking placebo. Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla
Next: Enthesitis

RESOLUTION OF PREEXISTING ENTHESITIS THROUGH WEEK 2082

Patients achieving resolution of preexisting enthesitis in PALACE 1-32,a-c

Secondary endpoint; data as observed

 

Includes all patients exposed to Otezla from baseline who completed treatment through week 208.

a

MASES score of 0 indicates the absence of pain in the 13 tested entheses.6,7

b

Data are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 208 weeks.

c

Patients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other).

d

n/N, number of responders/number of subjects who had sufficient data for a definitive determination of response status at the time point, which includes subjects who discontinued early between the preceding time point and the specific time point.

 

PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

 

Selected Safety Information

Warnings and Precautions

  • 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
Next: Axial Symptoms

MEAN CHANGE IN AXIAL SYMPTOMS THROUGH WEEK 522

Mean change in axial symptoms in PALACE 1-32,a,b

Prespecified exploratory endpoint; data as observed

Pooled analysis of PALACE 1-3 patients considered by investigators to have axial symptoms (baseline BASDAI ≥4), although axial involvement was not confirmed by MRI.8

 

Includes patients who were randomized to Otezla at baseline and remained on treatment for 52 weeks.

a

Data are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment for 52 weeks.

b

Prespecified pooled analysis; weeks 16, 24, and 52 were prespecified exploratory endpoints.

c

BASDAI is used to clinically assess possible axial involvement in psoriatic arthritis. It is a 6-item, self-administered questionnaire assessing levels of back pain, fatigue, peripheral joint pain and swelling, localized tenderness, and the duration and severity of morning stiffness. The final score ranges from 0 to 10, with a lower score denoting less severe axial symptoms.8-11

d

The n at each time point represents patients with a baseline value and a post-baseline value at the time point and includes subjects who discontinued early between the preceding time point and the specific time point.

 

MRI, magnetic resonance imaging; PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

 

Selected Safety Information

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); nasopharyngitis (2.6, 1.6); upper abdominal pain (2.0, 0.2)
Next: Fatigue

MEAN PERCENT CHANGE IN FATIGUE SCORE THROUGH WEEK 522

Mean percent change in fatigue score in PALACE 1-32,a,b

Prespecified secondary endpoint; data as observed

 

Includes patients who were randomized to Otezla at baseline and remained on treatment for 52 weeks.

a

Data are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 52 weeks.

b

Prespecified pooled analysis; weeks 16, 24, and 52 were prespecified secondary endpoints.

c

FACIT–F is a 13-item, self-administered questionnaire that assesses fatigue and its physical impact on daily activities and function. The total FACIT–F score ranges from 0 to 52, with lower scores denoting higher levels of fatigue.12

d

The n at each time point represents patients with a baseline value and a post-baseline value at the time point and includes subjects who discontinued early between the preceding time point and the specific time point.

 

PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

 

Selected Safety Information

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
Next: Physical Function

PHYSICAL FUNCTION RESPONSE THROUGH WEEK 2082

Mean change in HAQ–DI in PALACE 1-32,a-c

Secondary endpoint; data as observed

 

Includes all patients exposed to Otezla from baseline who completed treatment through week 208.

a

Data are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 208 weeks.

b

HAQ–DI is a 20-item, self-administered questionnaire that assesses a patient’s level of functional ability. The total HAQ–DI score ranges from 0 to 3, with 0 representing normal or no difficulty, and 3 representing inability to perform.13

c

Patients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other).

d

The n at each time point represents patients with a baseline value and a postbaseline value at the time point and includes subjects who discontinued early between the preceding time point and the specific time point.

Physical function was significantly improved at week 16 with Otezla 30 mg (-0.244, n = 159) vs placebo (-0.086, n = 165); P = 0.0017 in PALACE 1 (LOCF; FAS). Similar results were observed in PALACE 2 and 31,2,4,5

 

FAS, full analysis set; LOCF, last observation carried forward; PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

 

Selected Safety Information

Use in Specific Populations

  • 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
Next: PALACE 4: DMARD-naïve

Otezla significantly improved ACR20 response in DMARD-naïve patients at week 1614

ACR20 responders at week 16 (primary endpoint) in PALACE 414

Nonresponder imputation; full analysis set

ACR, American College of Rheumatology; BID, twice daily; DMARD, disease-modifying antirheumatic drug; PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

In PALACE 4:
  • The most common adverse reactions (reported in ≥5% of patients) on Otezla 30 mg twice daily through week 16 (N = 175) included diarrhea (11.4%), nausea (14.3%), and headache (8.0%)2*
  • Discontinuations due to any adverse reactions occurred at 5.2% during weeks 0 to ≤52, 3.5% during weeks >52 to ≤104, and 3.1% during weeks >104 to ≤156. There were no discontinuations during weeks >156 to ≤2082
*

Adverse reactions shown are those that occurred in 5% or more of patients receiving Otezla 30 mg twice daily through week 16, before early escape.2

PALACE 4 clinical trial program2,14

Program:

  • Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel group study
  • 527 DMARD-naïve adult patients with active psoriatic arthritis
  • Click here to see full study design for more information

ACR20 RESPONSE THROUGH WEEK 1562,14

ACR20 responders in PALACE 42,14,a,b

Secondary endpoint; data as observed

Includes all patients exposed to Otezla from baseline who completed treatment through week 156.

a

Data are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 156 weeks.

b

The percentages of patients achieving an ACR20 at week 16 differ between the primary endpoint and the data presented in the graph due to the use of different analyses. For the primary endpoint, data were analyzed using nonresponder imputation compared with the long-term data, which indicates data as observed.

c

n/N, number of responders/number of subjects who had sufficient data for a definitive determination of response status at the time point, which includes subjects who discontinued early between the preceding time point and the specific time point.

  • Patients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other)2,14
  • Placebo-controlled efficacy data were collected and analyzed through week 24. Placebo nonresponders at week 16 were re-randomized to either 20 mg twice daily or 30 mg twice daily Otezla. At week 24, all remaining patients receiving placebo were re-randomized to either 20 mg twice daily or 30 mg twice daily. Patients treated with Otezla remained on their initial treatment. Patients entering a long-term extension phase could be treated through 5 years14

 

MEAN REDUCTION IN JOINT TENDERNESS AND SWELLING THROUGH WEEK 1562

Mean percent reduction in tender and swollen joints in PALACE 42,a,b

Prespecified analysis; data as observed

Includes all patients exposed to Otezla from baseline who completed treatment through week 156.

a

Data are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 156 weeks.

b

Patients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other).

c

The n at each time point represents patients with a baseline value and a post-baseline value at the time point and includes subjects who discontinued early between the preceding time point and the specific time point.

Treatment with Otezla also significantly improved these measured ACR components vs placebo at week 16—pain and global disease activity assessed by patients, global disease activity assessed by physicians, and HAQ–DI14

HAQ–DI, Health Assessment Questionnaire–Disability Index.

RESOLUTION OF PREEXISTING DACTYLITIS THROUGH WEEK 1562

Patients achieving resolution of preexisting dactylitis in PALACE 42,a-c

Secondary endpoint; data as observed

Includes all patients exposed to Otezla from baseline who completed treatment through week 156.

a

Examined among patients with dactylitis (n = 84) at baseline. Dactylitis Severity Score of 0 indicates that all digits in the hands and feet are free of dactylitis.

b

Data are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 156 weeks.

c

Patients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other).

d

n/N, number of responders/number of subjects who had sufficient data for a definitive determination of response status at the time point, which includes subjects who discontinued early between the preceding time point and the specific time point.

 

RESOLUTION OF PREEXISTING ENTHESITIS THROUGH WEEK 1562

Patients achieving resolution of preexisting enthesitis in PALACE 42,a-c

Secondary endpoint; data as observed

Includes all patients exposed to Otezla from baseline who completed treatment through week 156.

a

Data are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 156 weeks.

b

Examined among patients with enthesitis (n = 111) at baseline. MASES score of 0 indicates the absence of pain in the 13 tested entheses.

c

Patients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other).

d

n/N, number of responders/number of subjects who had sufficient data for a definitive determination of response status at the time point, which includes subjects who discontinued early between the preceding time point and the specific time point.

PATIENT'S ASSESSMENT OF PAIN THROUGH WEEK 1562

Mean change in pain VAS in PALACE 42,a-c

Secondary endpoint; data as observed

Includes all patients exposed to Otezla from baseline who completed treatment through week 156.

a

Data are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 156 weeks.

b

Patients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other).

c

Pain was assessed on a 0-100 mm VAS.

d

Mean patientʼs assessment of pain VAS score at baseline for patients receiving Otezla 30 mg twice daily: 53.

e

The n at each time point represents patients with a baseline value and a post-baseline value at the time point and includes subjects who discontinued early between the preceding time point and the specific time point.

PHYSICAL FUNCTION RESPONSE THROUGH WEEK 1562

Mean change in HAQ–DI in PALACE 42,a-c

Secondary endpoint; data as observed

Includes all patients exposed to Otezla from baseline who completed treatment through week 156.

a

Data are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 156 weeks.

b

HAQ–DI is a 20-item, self-administered questionnaire that assesses a patient's level of functional ability. The total HAQ–DI score ranges from 0 to 3, with 0 representing normal or no difficulty, and 3 representing inability to perform.13

c

Patients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other).

d

The n at each time point represents patients with a baseline value and a post-baseline value at the time point and includes subjects who discontinued early between the preceding time point and the specific time point.

Selected 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 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
Next: ACTIVE: Biologic-naïve

Otezla significantly improved ACR20 response in biologic-naïve patients at week 162,15

The primary endpoint of ACR20 response at week 16 was significantly greater with Otezla 30 mg BID (38.2%, n = 110) vs placebo (20.2%, n = 109); P = 0.004015
(nonresponder imputation; full analysis set)

ACR, American College of Rheumatology; BID, twice daily.

ACTIVE clinical trial program2,15

Program:

  • Phase IIIb, multicenter, randomized, double-blind, placebo-controlled, parallel group study
  • 219 adult patients with active psoriatic arthritis
  • Click here to see full study design for more information

ACR20 RESPONSE THROUGH WEEK 5215

ACR20 responders in the ACTIVE® trial15,a

Secondary endpoint; data as observed

a

Data are presented "as observed" with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 52 weeks.

b

Includes all patients exposed to Otezla from baseline who completed treatment through week 52.

c

At week 16, patients receiving placebo were eligible to be switched to Otezla; at week 24, all remaining patients receiving placebo were switched to Otezla. Only patients who received ≥1 dose of Otezla were included.

d

n/N, number of responders/number of subjects who had sufficient data for a definitive determination of response status at the time point, which includes subjects who discontinued early between the preceding time point and the specific time point.

 

ACTIVE, Assessing Apremilast Monotherapy in a Clinical Trial of Biologic-Naïve Patients With Psoriatic Arthritis.

  • Statistical significance was not reached for the first secondary endpoint. Hierarchical testing was therefore stopped, making the remaining secondary endpoints statistically nonsignificant15
In ACTIVE:
  • The most common adverse reactions (reported in ≥5% of patients) during the apremilast exposure period (n = 206) included diarrhea (16.0%); nausea (7.8%); nasopharyngitis (7.8%); headache (5.8%); hypertension (6.3%); upper respiratory tract infection (6.8%)15
  • Discontinuations due to any adverse reactions occurred at 8.3% during the apremilast exposure period (n = 206)15

JOINT TENDERNESS REDUCTION THROUGH WEEK 522

Mean percent reduction in tender joints in the ACTIVE trial2,a

Exploratory analysis; data as observed

a

Data are presented "as observed" with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 52 weeks.

b

Includes all patients exposed to Otezla from baseline who completed treatment through week 52.

c

At week 16, patients receiving placebo were eligible to be switched to Otezla; at week 24, all remaining patients receiving placebo were switched to Otezla. Only patients who received ≥1 dose of Otezla were included.

d

The n at each time point represents patients with a baseline value and a post-baseline value at the time point and includes subjects who discontinued early between the preceding time point and the specific time point.

JOINT SWELLING REDUCTION THROUGH WEEK 522

Mean percent reduction in swollen joints in the ACTIVE trial2,a

Exploratory analysis; data as observed

a

Data are presented "as observed" with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 52 weeks.

b

Includes all patients exposed to Otezla from baseline who completed treatment through week 52.

c

At week 16, patients receiving placebo were eligible to be switched to Otezla; at week 24, all remaining patients receiving placebo were switched to Otezla. Only patients who received ≥1 dose of Otezla were included.

d

The n at each time point represents patients with a baseline value and a post-baseline value at the time point and includes subjects who discontinued early between the preceding time point and the specific time point.

 

Selected Safety Information

Warnings and Precautions (cont'd)

  • Depression: 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 (0/495). 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
Next: Safety

References: 1. Otezla [package insert]. Thousand Oaks, CA: Amgen Inc. 2. Data on file, Amgen Inc. 3. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. J Rheumatol. 2015;42(3):479-488. 4. Cutolo M, Myerson GE, Fleischmann RM, et al. J Rheumatol. 2016;43(9):1724-1734. 5. Edwards CJ, Blanco JC, Crowley J, et al. Ann Rheum Dis. 2016;75(6):1065-1073. 6. Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, et al. Ann Rheum Dis. 2003;62:127-132. 7. Marchesoni A, Cantini F. Reumatismo. 2012;64(2):79-87. 8. Mease PJ, Marzo-Ortega H, Poder A, et al. Apremilast, an Oral Phosphodiesterase 4 Inhibitor, Is Associated With Long-term (52-Week) Improvements in BASDAI in Patients With Psoriatic Arthritis: Pooled Results From 3 Phase III, Randomized, Controlled Trials. Presented at: the Annual European Congress of Rheumatology EULAR 2016; 8-11 June 2016; London, UK. 9. Zochling J. Arthritis Care Res. 2011;63(11):S47-S58. 10. Fernandez-Sueiro JL, Willisch A, Pertega-Diaz S, et al. Arthritis Care Res. 2010;62(1):78-85. 11. Nash P, Lubrano E, Cauli A, Taylor WJ, Olivieri I, Gladman DD. J Rheumatol. 2014;41(11):2286-2289. 12. Cella D, Lai JS, Chang CH, Peterman A, Slavin M. Cancer. 2002;94(2):528-538. 13. Bruce B, Fries JF. J Rheumatol. 2003;30(1):167-178. 14. Wells AF, Edwards CJ, Kivitz AJ, et al. Rheumatology (Oxford). 2018;57(7):1253-1263. 15. Nash P, Ohson K, Walsh J, et al. Ann Rheum Dis. doi:10.1136/annrheumdis-2017-211568.

INDICATIONS & IMPORTANT SAFETY INFORMATION

INDICATIONS

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

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% (1/1 308) of patients exposed to Otezla, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1%(1/1 308) of patients on Otezla, compared to 0.2% (1/506) on placebo. One patient treated with Otezia 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% (3/1 441) of patients on Otezla, compared to none in placebo-treated patients. Depression was reported as serious in 0.2% (3/1 441) 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
    • Behcet’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% (1 9/382) 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 ¡n 3.9% (4/102) of patients taking placebo
  • Drug Interactions: Apremilast exposure was decreased when Otezla was co-administered with rilampin, a strong CYP4SO enzyme inducer; loss of Otezla efficacy may occur. Concomitant use of Otezla with CYP45O enzyme inducers (e.g., rifampin. phenobarbital, carbamazepine, phenytoin) is not recommended

Adverse Reactions

  • Psoriasis: Adverse reactions reported in ≥5% of patients were (Otezla%, ptacebo%): 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 (east 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 (2M, 0.2)
  • Behçet’s Disease: Adverse reactions reported in 5% of patients taking Otezta, 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://mothertoaby.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 breastleeding should be considered along with the mother’s clinical need for Otezla and any potential adverse effects on the breastled 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/mm); for details, see Dosage and Administration, Section 2, in the Full Prescribing Information

Please click here for Full Prescribing Information.

INDICATIONS & IMPORTANT SAFETY INFORMATION

INDICATIONS

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

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% (1/1 308) of patients exposed to Otezla, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1%(1/1 308) of patients on Otezla, compared to 0.2% (1/506) on placebo. One patient treated with Otezia 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% (3/1 441) oF patients on Otezla, compared to none in placebo-treated patients. Depression was reported as serious in 0.2% (3/1 441) 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
    • Behcet’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% (1 9/382) 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 ¡n 3.9% (4/102) of patients taking placebo
  • Drug Interactions: Apremilast exposure was decreased when Otezla was co-administered with rilampin, a strong CYP4SO enzyme inducer; loss of Otezla efficacy may occur. Concomitant use of Otezla with CYP45O enzyme inducers (e.g., rifampin. phenobarbital, carbamazepine, phenytoin) is not recommended

Adverse Reactions

  • Psoriasis: Adverse reactions reported in ≥5% of patients were (Otezla%, ptacebo%): 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 (east 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 (2M, 0.2)
  • Behçet’s Disease: Adverse reactions reported in 5% of patients taking Otezta, 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 letal 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 breastleeding should be considered along with the mother’s clinical need for Otezla and any potential adverse effects on the breastled 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/mm); for details, see Dosage and Administration, Section 2, in the Full Prescribing Information

Please click here for Full Prescribing Information.