Efficacy

Results from Otezla^® (apremilast) clinical trials

ACR20
Response
Joint
Tenderness
and Swelling
Dactylitis
Enthesitis
Axial Symptoms
Fatigue
Physical
Function
PALACE 4:
DMARD-naïve
ACTIVE:
Biologic-naïve

OTEZLA SIGNIFICANTLY IMPROVED ACR20 RESPONSE, WITH OR WITHOUT DMARDs^1-3

ACR20 responders at week 16 (primary endpoint) in PALACE™ 1^1-3

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 analysis^1,2,4,5
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; PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

ACR20 RESPONSE THROUGH WEEK 208^2,3

ACR20 responders in PALACE 1^2,3,a

Secondary endpoint; data as observed

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

^aData 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. ^bn/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 years^1-3

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

Mean reduction in joint tenderness and swelling through week 208^2,3

Mean percent reduction in tender and swollen joints in PALACE 1^2,3,a,b

Prespecified analysis; data as observed

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

^aData 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. ^bPatients 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). ^cThe 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 (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

RESOLUTION OF PREEXISTING DACTYLITIS THROUGH WEEK 208²

Patients achieving resolution of preexisting dactylitis in PALACE 1-3^2,a-c

Secondary endpoint; data as observed

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

^aDactylitis Severity Score of 0 indicates that all digits in the hands and feet are free of dactylitis. ^bData 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. ^cPatients 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). ^dn/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 (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

RESOLUTION OF PREEXISTING ENTHESITIS THROUGH WEEK 208²

Patients achieving resolution of preexisting enthesitis in PALACE 1-3^2,a-c

Secondary endpoint; data as observed

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

^aMASES score of 0 indicates the absence of pain in the 13 tested entheses.^6,7 ^bData 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. ^cPatients 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). ^dn/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 (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

MEAN CHANGE IN AXIAL SYMPTOMS THROUGH WEEK 52²

Mean change in axial symptoms in PALACE 1-3^2,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.

^aData 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. ^bPrespecified pooled analysis; weeks 16, 24, and 52 were prespecified exploratory endpoints. ^cBASDAI 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 ^dThe 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)

MEAN PERCENT CHANGE IN FATIGUE SCORE THROUGH WEEK 52²

Mean percent change in fatigue score in PALACE 1-3^2,a,b

Prespecified secondary endpoint; data as observed

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

^aData 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. ^bPrespecified pooled analysis; weeks 16, 24, and 52 were prespecified secondary endpoints. ^cFACIT–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 ^dThe 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

PHYSICAL FUNCTION RESPONSE THROUGH WEEK 208²

Mean change in HAQ–DI in PALACE 1-3^2,a-c

Secondary endpoint; data as observed

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

^aData 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. ^bHAQ–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 ^cPatients 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). ^dThe 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 3^1,2,4,5

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 (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

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 program^2,14

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 (select PALACE 4 Clinical Trial Program tab)

ACR20 RESPONSE THROUGH WEEK 156^2,14

ACR20 responders in PALACE 4^2,14,a,b

Secondary endpoint; data as observed

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

aData 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. bThe 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. cn/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 4^2,a,b

Prespecified analysis; data as observed

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

aData 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. bPatients 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). cThe 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 4^2,a-c

Secondary endpoint; data as observed

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

aExamined 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. bData 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. cPatients 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). dn/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 4^2,a-c

Secondary endpoint; data as observed

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

aData 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. bExamined among patients with enthesitis (n = 111) at baseline. MASES score of 0 indicates the absence of pain in the 13 tested entheses. cPatients 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). dn/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 4^2,a-c

Secondary endpoint; data as observed

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

aData 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. bPatients 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). cPain was assessed on a 0-100 mm VAS. dMean patientʼs assessment of pain VAS score at baseline for patients receiving Otezla 30 mg twice daily: 53. eThe 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 4^2,a-c

Secondary endpoint; data as observed

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

aData 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. bHAQ–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 cPatients 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). dThe 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.