Phase II Study of Apremilast (CC-10004) in Adults With in Psoriatic Arthritis

• ClinicalTrials.gov Identifier: NCT00456092
• Recruitment Status: Completed
• First Posted: April 4, 2007
• Results First Posted: October 23, 2019
• Last Update Posted: June 19, 2020
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Psoriatic Arthritis
• Interventions: Drug: Apremilast; Drug: Placebo
• Enrollment: 204

Participant Flow

Recruitment Details	Participants were enrolled across 38 sites in Canada, Belgium, Germany, the Netherlands, and the United Kingdom.
Pre-assignment Details	Participants were randomized 1:1:1 to either apremilast 40 mg once daily, 20 mg twice daily, or placebo. On Day 85 participants originally randomized to placebo were re-randomized to receive apremilast; participants randomized to apremilast continued on the same dose regimen. Randomization was stratified based on methotrexate use at baseline.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description	Participants received 40 mg apremilast orally once a day (QD) for 12 weeks in the Treatment Phase. Participants who entered the Extension Phase continued to receive 40 mg apremilast QD for an additional 12 weeks. The dose of apremilast was titrated starting at 10 mg QD during Days 1 to 3 followed by 20 mg QD during Days 4 to 7 and then 40 mg QD thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication.	Participants received 20 mg apremilast orally twice a day (BID) for 12 weeks in the Treatment Phase. Participants who entered the Extension Phase continued to receive 20 mg apremilast BID for an additional 12 weeks. The dose of apremilast was titrated starting at 10 mg QD during Days 1 to 3 followed by 20 mg QD during Days 4 to 7 and then 20 mg BID thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication.	Participants received matching placebo to apremilast orally BID for 12 weeks during the Treatment Phase. Participants who entered the Extension Phase were re-randomized on Day 85 to receive either 40 mg apremilast QD or 20 mg apremilast BID for 12 weeks.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase. The dose of apremilast was titrated starting at 10 mg QD during Days 85 to 87 followed by 20 mg QD during Days 88 to 91 and then 40 mg QD thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase. The dose of apremilast was titrated starting at 10 mg QD during Days 85 to 87 followed by 20 mg QD during Days 88 to 91 and then 20 mg BID thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication.
Period Title: Extension Phase
Started	46 [1]	40 [1]	0	20 [1]	20 [1]
Completed	35	36	0	19	13
Not Completed	11	4	0	1	7
Reason Not Completed
Grade 2 or Greater AE	2	2	0	0	2
Flare of Psoriatic Arthritis	1	0	0	0	1
Worsening / Not Responding to Study Drug	3	1	0	0	2
Withdrew Consent	2	0	0	0	0
Lost to Follow-up	1	1	0	0	1
Other	2	0	0	1	1
[1] The Extension Phase was only open to participants enrolled after amendment 1 was in effect.
Period Title: Treatment Phase (12 Weeks)
Started	67	69	68	0	0
Completed	60	55	50	0	0
Not Completed	7	14	18	0	0
Reason Not Completed
Grade 2 or Greater Adverse Event (AE)	3	4	2	0	0
AEs not Included in NCI Terminology	1	2	0	0	0
Intolerability of the Study Drug	2	0	0	0	0
Flare of Psoriasis	0	1	2	0	0
Flare of Psoriatic Arthritis	0	3	3	0	0
Worsening / Not Responding to Study Drug	0	2	7	0	0
Withdrew Consent	0	1	2	0	0
Lost to Follow-up	0	1	1	0	0
Other	1	0	1	0	0

Baseline Characteristics

Arm/Group Title		Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo	Total
Arm/Group Description		Participants received 40 mg apremilast once daily (QD) for 12 weeks in the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks in the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Total of all reporting groups
Overall Number of Baseline Participants		67	69	68	204
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	67 participants	69 participants	68 participants	204 participants
		49.9 (11.17)	50.9 (12.58)	51.1 (10.80)	50.6 (11.50)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	67 participants	69 participants	68 participants	204 participants
	Female	35 52.2%	26 37.7%	36 52.9%	97 47.5%
	Male	32 47.8%	43 62.3%	32 47.1%	107 52.5%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	67 participants	69 participants	68 participants	204 participants
	White	62 92.5%	67 97.1%	68 100.0%	197 96.6%
	Black	1 1.5%	0 0.0%	0 0.0%	1 0.5%
	Hispanic	1 1.5%	0 0.0%	0 0.0%	1 0.5%
	Asian/Pacific Islander	2 3.0%	1 1.4%	0 0.0%	3 1.5%
	American Indian/Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Other	1 1.5%	1 1.4%	0 0.0%	2 1.0%
Psoriatic Arthritis Disease Category; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	67 participants	69 participants	68 participants	204 participants
	Asymmetrical Oligoarthritis	26 38.8%	21 30.4%	20 29.4%	67 32.8%
	Predominant Spondylitis	4 6.0%	3 4.3%	2 2.9%	9 4.4%
	Symmetric Polyarthritis	32 47.8%	36 52.2%	39 57.4%	107 52.5%
	Arthritis Mutilans	2 3.0%	0 0.0%	5 7.4%	7 3.4%
	Predominant Distal Interphalgeal Involvement	2 3.0%	9 13.0%	2 2.9%	13 6.4%
	Missing/Unknown	1 1.5%	0 0.0%	0 0.0%	1 0.5%
Duration of Psoriatic Arthritis; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	67 participants	69 participants	68 participants	204 participants
		7.6 (8.73)	8.4 (9.77)	7.3 (6.74)	7.8 (8.48)
Pain/Tender Joint Score [1]; Mean (Standard Deviation); Unit of measure: Joints
	Number Analyzed	67 participants	69 participants	68 participants	204 participants
		23.2 (17.63)	20.6 (15.90)	21.3 (15.55)	21.7 (16.33)
		[1] Measure Description: The number of tender joints (joints with scores of 1 to 3), rated on a scale of 0 (no pain/tenderness) to 3 (severe pain - tender, winced, withdrew). The joint count included the 68 joints routinely utilized in the American College of Rheumatology (ACR) joint count for evaluation of rheumatoid arthritis, plus 10 additional joints often involved in psoriatic arthritis (the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers) for a total of 78 joints.
Swollen Joint Score [1]; Mean (Standard Deviation); Unit of measure: Joints
	Number Analyzed	67 participants	69 participants	68 participants	204 participants
		8.4 (4.94)	10.6 (9.88)	9.5 (9.68)	9.5 (8.51)
		[1] Measure Description: The number of swollen joints noted by the examiner. The joint count included the 66 joints routinely utilized in the American College of Rheumatology (ACR) joint count for evaluation of rheumatoid arthritis, plus 10 additional joints often involved in psoriatic arthritis (the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers) for a total of 76 joints.
Psoriasis Severity [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	67 participants	69 participants	68 participants	204 participants
	None	2 3.0%	7 10.1%	12 17.6%	21 10.3%
	Mild	41 61.2%	47 68.1%	40 58.8%	128 62.7%
	Moderate	20 29.9%	15 21.7%	11 16.2%	46 22.5%
	Severe	4 6.0%	0 0.0%	5 7.4%	9 4.4%
		[1] Measure Description: Psoriasis severity was assessed by the Investigator.
Duration of Psoriasis; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	67 participants	69 participants	68 participants	204 participants
		18.3 (13.62)	15.5 (11.66)	15.8 (13.22)	16.5 (12.85)
Methotrexate Use; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	67 participants	69 participants	68 participants	204 participants
	Yes	30 44.8%	30 43.5%	29 42.6%	89 43.6%
	No	37 55.2%	39 56.5%	39 57.4%	115 56.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Modified American College of Rheumatology 20% (ACR 20) Response at Week 12
Description	A modified American College of Rheumatology 20% (ACR 20) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 20% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. Participants with no post-baseline ACR scores were considered non-responders.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population which consisted of all randomized participants with at least one of the ACR components assessed at baseline. Last observation carried forward (LOCF) imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	68
Measure Type: Number; Unit of Measure: percentage of participants
	35.8	43.5	11.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	A p-value < 0.025 (2-sided) is considered statistically significant, after adjusting for two treatment comparisons using the Bonferroni procedure.
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.190
	Confidence Interval	(2-Sided) 95%; 1.72 to 10.20
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	A p-value < 0.025 (2-sided) is considered statistically significant, after adjusting for two treatment comparisons using the Bonferroni procedure.
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.770
	Confidence Interval	(2-Sided) 95%; 2.40 to 13.88
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Number of Participants With Adverse Events During the Treatment Phase
Description	The severity of each adverse event (AE) was graded based upon the participant's symptoms according to National Cancer Institute (NCI) Common Toxicity Criteria (CTCAE, Version 3.0), on a scale from 1 (Mild AE) to 5 (Death due to AE). Severe AEs are defined as NCI CTCAE grade 3 or higher. AEs related to study drug are those determined by the investigator as suspected to be related to study drug where a temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other medications, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. A serious adverse event (SAE) is any AE which: - Resulted in death - Was life-threatening - Required inpatient hospitalization or prolongation of existing hospitalization - Resulted in persistent or significant disability/incapacity - Was a congenital anomaly/birth defect - Constituted an important medical event.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The safety population which consisted of all enrolled participants who received at least 1 dose of study medication.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	68
Measure Type: Count of Participants; Unit of Measure: Participants
All adverse events	58 86.6%	59 85.5%	55 80.9%
Adverse events related to study drug	27 40.3%	26 37.7%	26 38.2%
Severe adverse events	5 7.5%	4 5.8%	6 8.8%
Severe adverse events related to study drug	1 1.5%	1 1.4%	1 1.5%
Serious adverse events	0 0.0%	4 5.8%	4 5.9%
Serious adverse events related to study drug	0 0.0%	0 0.0%	1 1.5%
Discontinued study drug due to adverse event	6 9.0%	10 14.5%	7 10.3%
Discontinued due to AE related to study drug	5 7.5%	4 5.8%	1 1.5%

3. Secondary Outcome

Title	Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 12
Description	A PsARC response is defined as improvement from Baseline in at least 2 of the following 4 measures, at least 1 of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures, according to the following: • At least 30% improvement in the 78 tender joint count, • At least 30% improvement in the 76 swollen joint count, • At least 20% improvement in the patient global assessment of disease activity, measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • At least 20% improvement in the physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Participants with no post-baseline PsARC scores were considered non-responders.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	68
Measure Type: Number; Unit of Measure: percentage of participants
	50.7	52.2	22.1

4. Secondary Outcome

Title	Percentage of Participants With a Modified ACR 50 Response at Week 12
Description	A modified American College of Rheumatology 50% (ACR 50) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 50% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. Participants with no post-baseline ACR scores were considered non-responders.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	68
Measure Type: Number; Unit of Measure: percentage of participants
	13.4	17.4	2.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.056
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.120
	Confidence Interval	(2-Sided) 95%; 1.06 to 24.67
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.012
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	6.950
	Confidence Interval	(2-Sided) 95%; 1.49 to 32.35
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Percentage of Participants With a Modified ACR 70 Response at Week 12
Description	A modified American College of Rheumatology 70% (ACR 70) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 70% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-reactive protein. Participants with no post-baseline ACR scores were considered non-responders.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	68
Measure Type: Number; Unit of Measure: percentage of participants
	7.5	5.8	1.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.204
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.400
	Confidence Interval	(2-Sided) 95%; 0.61 to 47.54
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.371
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.120
	Confidence Interval	(2-Sided) 95%; 0.45 to 37.88
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response Based on Disease Activity Score (DAS28)-CRP(4) at Week 12
Description	The DAS28 measures the severity of disease at a specific time. DAS28-CRP(4) is derived from the following 4 variables: • 28 tender joint count, (TJC; does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count (SJC) • C-reactive protein (CRP) • Patient's global assessment of disease activity (GH) according to the formula: DAS28-CRP(4) = 0.56*√(TJC28) + 0.28*(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96. DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity. A EULAR response reflects an improvement in disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and a DAS28 score ≤ 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; LOCF imputation was used. Participants with no baseline or post-baseline DAS28-CRP(4) scores were considered non-responders.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	68
Measure Type: Number; Unit of Measure: percentage of participants
	49.3	55.1	38.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.264
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.568
	Confidence Interval	(2-Sided) 95%; 0.79 to 3.11
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.071
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.980
	Confidence Interval	(2-Sided) 95%; 1.00 to 3.91
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 12
Description	The DAS28 measures the severity of disease at a specific time. DAS28-CRP(3) is derived from the following 3 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) according to the formula: DAS28-CRP(3) = [0.56*√(TJC28) + 0.28*√(SJC28) + 0.36*ln(CRP+1)] * 1.10 + 1.15. DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity. A EULAR response reflects an improvement in disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and attainment of a DAS28 score ≤ 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; LOCF imputation was used. Participants with no baseline or post-baseline DAS28-CRP(3) scores were considered non-responders.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	68
Measure Type: Number; Unit of Measure: percentage of participants
	50.7	44.9	44.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.549
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.305
	Confidence Interval	(2-Sided) 95%; 0.66 to 2.57
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	1.000
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.033
	Confidence Interval	(2-Sided) 95%; 0.53 to 2.03
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Percentage of Participants With DAS28-CRP(4) Score of Mild Disease Activity or In Remission at Week 12
Description	The DAS28-CRP(4) measures the severity of disease derived from the following 4 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28-CRP(4) scores range from 0 to 9.4, where higher scores indicate more disease activity. Mild disease severity is defined as a DAS28-CRP(4) score of ≤ 3.2. In remission is defined as a DAS28-CRP(4) score of ≤ 2.6.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; LOCF imputation was used. Participants with no post-baseline DAS28-CRP(4) scores were considered non-responders.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	68
Measure Type: Number; Unit of Measure: percentage of participants
	38.8	33.3	23.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.083
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.060
	Confidence Interval	(2-Sided) 95%; 0.98 to 4.34
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.279
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.630
	Confidence Interval	(2-Sided) 95%; 0.77 to 3.44
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Percentage of Participants With DAS28-CRP(3) Score of Mild Disease Activity or In Remission at Week 12
Description	The DAS28-CRP(3) measures the severity of disease derived from the following 3 variables: • 28 tender joint count (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) DAS28-CRP(3) scores range from 0 to 9.4, where higher scores indicate more disease activity. Mild disease severity is defined as a DAS28-CRP(3) score of ≤ 3.2. In remission is defined as a DAS28-CRP(3) score of ≤ 2.6.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; LOCF imputation was used. Participants with no post-baseline DAS28-CRP(3) scores were considered non-responders.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	68
Measure Type: Number; Unit of Measure: percentage of participants
	40.3	34.8	33.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.548
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.320
	Confidence Interval	(2-Sided) 95%; 0.66 to 2.66
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	1.000
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.040
	Confidence Interval	(2-Sided) 95%; 0.52 to 2.11
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Number of Participants Who Withdrew Prematurely Due to Lack of Efficacy
Description	The number of participants who withdrew prematurely from the treatment phase due to lack of efficacy, including flare of psoriasis, flare of psoriatic arthritis or worsening or not responding to study treatment.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	68
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	6 8.7%	12 17.6%

11. Secondary Outcome

Title	Number of Participants With Adverse Events Leading to a Dose Reduction
Description	The number of participants who were dose reduced during the treatment phase due to adverse events.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	68
Measure Type: Count of Participants; Unit of Measure: Participants
	4 6.0%	4 5.8%	0 0.0%

12. Secondary Outcome

Title	Maximal ACR Response During the Treatment Phase
Description	The ACR-N index score was calculated for each participant at each time point in the study according to the following definition: ACR-N = the lowest of the following 3 values: - percent improvement from Baseline in the 76 swollen joint count, - percent improvement from Baseline in the 78 tender joint count - median percent improvement from Baseline in the following 5 measures ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. The maximal ACR-N for each participant during the 12-week treatment period was calculated, and represents the maximal ACR response achieved.
Time Frame	ACR was measured at Baseline and Weeks 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with non-missing ACR data

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	65	67	65
Mean (Standard Deviation); Unit of Measure: percent improvement
	22.3 (56.45)	24.2 (37.63)	10.7 (35.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.136
	Comments	[Not Specified]
	Method	ANOVA
	Comments	ANOVA model with treatment as the factor.
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	11.58
	Estimation Comments	Treatment Difference = Apremilast 20 mg BID - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.080
	Comments	[Not Specified]
	Method	ANOVA
	Comments	ANOVA model with treatment as the factor.
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	13.53
	Estimation Comments	Treatment Difference = Apremilast 20 mg BID - Placebo

13. Secondary Outcome

Title	Time to ACR 20 Response During the Treatment Phase
Description	The Kaplan-Meier estimates of time to ACR 20 response was calculated for participants who had an ACR 20 response at any time during the treatment phase.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with an ACR 20 response during the treatment phase.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	37	43	31
Median (95% Confidence Interval); Unit of Measure: days
	29.0; (29.0 to 43.0)	30.0; (29.0 to 57.0)	29.0; (20.0 to 47.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.650
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.950
	Confidence Interval	(2-Sided) 95%; 0.745 to 1.211
	Estimation Comments	Based on a proportional hazards model comparing the hazard functions associated with the treatment and placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.283
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.265
	Confidence Interval	(2-Sided) 95%; 0.791 to 2.024
	Estimation Comments	Based on a proportional hazards model comparing the hazard functions associated with the treatment and placebo.

14. Secondary Outcome

Title	Time to ACR 50 Response During the Treatment Phase
Description	The Kaplan-Meier estimates of time to ACR 50 response was calculated for participants who had an ACR 50 response at any time during the treatment phase.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population who had an ACR 50 response during the treatment phase.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	17	18	5
Median (95% Confidence Interval); Unit of Measure: days
	43.0; (29.0 to 61.0)	57.5; (56.0 to 72.0)	15.0; (14.0 to 73.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.253
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.337
	Confidence Interval	(2-Sided) 95%; 0.791 to 2.260
	Estimation Comments	Based on a proportional hazards model comparing the hazard functions associated with the treatment and placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.026
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	3.023
	Confidence Interval	(2-Sided) 95%; 1.059 to 8.630
	Estimation Comments	Based on a proportional hazards model comparing the hazard functions associated with the treatment and placebo.

15. Secondary Outcome

Title	Time to ACR 70 Response During the Treatment Phase
Description	The Kaplan-Meier estimates of time to ACR 70 response was calculated for participants who had an ACR 70 response at any time during the treatment phase.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with an ACR 70 response during the treatment phase.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	7	5	2
Median (95% Confidence Interval); Unit of Measure: days
	62.0; (47.0 to 85.0)	57.0; (43.0 to 85.0)	58.0; (31.0 to 85.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.984
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.006
	Confidence Interval	(2-Sided) 95%; 0.457 to 2.215
	Estimation Comments	Based on a proportional hazards model comparing the hazard functions associated with the treatment and placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.836
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.872
	Confidence Interval	(2-Sided) 95%; 0.158 to 4.797
	Estimation Comments	Based on a proportional hazards model comparing the hazard functions associated with the treatment and placebo.

16. Secondary Outcome

Title	Change From Baseline in Dactylitis Severity Score at Week 12
Description	Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated on a scale from 0 (no dactylitis) to 3 (severe dactylitis). The dactylitis severity score is the sum of the individual scores for each digit and ranges from 0 to 60.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; participants with a baseline value and at least 1 post-baseline value in the treatment period are included; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	67	67
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.9 (2.39)	-1.2 (3.11)	-0.2 (3.75)

17. Secondary Outcome

Title	Percentage of Participants With Enthesitis
Description	Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. Enthesitis is characterized by swelling, pain, and tenderness around the calcaneous, and occasionally by effusion in the bursa associated with this joint. The enthesitis assessment is an evaluation of inflammation at the insertions of the Achilles tendon into the calcaneous and of the plantar fascia into the calcaneous. Inflammation at 1 or more insertions on either the right or left side constituted a positive assessment.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	68
Measure Type: Number; Unit of Measure: percentage of participants
Achilles tendon into the calcaneous: Baseline	22.4	21.7	35.3
Achilles tendon into the calcaneous: Week 12	20.9	17.4	17.6
Plantar fascia into the calcaneous: Baseline	26.9	26.1	14.7
Plantar fascia into the calcaneous: Week 12	19.4	21.7	17.6

18. Secondary Outcome

Title	Time to Relapse of Psoriatic Arthritis During the Observational Follow-up Phase
Description	Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Observation Phase in participants who received apremilast and achieved at least an ACR 20 at their Final Treatment Phase/Early Termination Visit. The time to relapse during the Observational Phase was calculated from the time of maximum ACR reduction and from the date of the Final Treatment Phase visit. Participants classified as responders who did not relapse were censored at the day of the last follow-up.
Time Frame	From Week 12 to end of 28-day observational follow-up (1) and from the date of maximal ACR during the 12-week Treatment Phase until the end of the 28-day observational follow-up phase (2).

Outcome Measure Data

Analysis Population Description

Participants who received apremilast and with an ACR 20 response at the Week 12 (or Early Termination) visit who did not enroll in the Extension Phase.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	7	11
Median (95% Confidence Interval); Unit of Measure: days
1. From Week 12	16.0; (15.0 to 29.0)	15.0; (14.0 to 29.0)
2. From Date of Maximal ACR Response	43.0; (34.0 to 73.0)	29.0; (22.0 to 43.0)

19. Secondary Outcome

Title	Number of Participants Who Relapsed During the Observational Follow-up Phase
Description	Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Observation Phase in participants who received apremilast and achieved at least an ACR 20 at their Final Treatment Phase/Early Termination Visit.
Time Frame	28-day observational follow-up period following Week 12

Outcome Measure Data

Analysis Population Description

Participants who received apremilast with an ACR 20 response at the Week 12 (or Early Termination) visit who did not enroll in the Extension Phase.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	7	11
Measure Type: Count of Participants; Unit of Measure: Participants
	5 71.4%	9 81.8%

20. Secondary Outcome

Title	Change From Baseline in Short Form 36 (SF-36) Summary Physical and Mental Component Scores at Week 12
Description	The Medical Outcome SF 36-Item Health Survey, Version 2 is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The summary physical health score included the following subscales: physical functioning, role-physical, bodily pain, and general health. The summary mental health score included other subscales: vitality, social functioning, role-emotional, and mental health. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10, where higher scores are associated with better functioning/quality of life. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale. A higher change from baseline indicates an improvement in better health results or functioning.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; participants with a baseline value and at least 1 post-baseline value in the treatment period are included; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	65	64	61
Mean (Standard Deviation); Unit of Measure: units on a scale
Mental Component	1.0 (8.01)	3.4 (7.18)	-0.8 (8.39)
Physical Component	2.1 (5.94)	2.4 (7.89)	0.8 (6.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	Mental Component
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.308
	Comments	[Not Specified]
	Method	ANOVA
	Comments	ANOVA model including treatment group, methotrexate use, and baseline score.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1.4
	Estimation Comments	Adjusted mean difference (Apremilast-Placebo) was based on the ANOVA model described above.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	Mental Component
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.003
	Comments	[Not Specified]
	Method	ANOVA
	Comments	ANOVA model including treatment group, methotrexate use, and baseline score.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	4.1
	Estimation Comments	Adjusted mean difference (Apremilast-Placebo) was based on the ANOVA model described above.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	Physical Component
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.182
	Comments	[Not Specified]
	Method	ANOVA
	Comments	ANOVA model including treatment group, methotrexate use, and baseline score.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1.6
	Estimation Comments	Adjusted mean difference (Apremilast-Placebo) was based on the ANOVA model described above.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	Physical Component
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.026
	Comments	[Not Specified]
	Method	ANOVA
	Comments	ANOVA model including treatment group, methotrexate use, and baseline score.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	2.7
	Estimation Comments	Adjusted mean difference (Apremilast-Placebo) was based on the ANOVA model described above.

21. Secondary Outcome

Title	Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 12
Description	The DLQI is a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on participants' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, leisure, work, personal relationships, and treatment. Each question is answered on a scale from 0 (not at all) to 3 (very much). The total score ranges from 0 to 30 where a higher score indicates that a participant's dermatological condition has a greater impact on their daily life.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; participants with a baseline value and at least 1 post-baseline value in the treatment period are included; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	67	64
Mean (Standard Deviation); Unit of Measure: units on a scale
	-2.6 (5.96)	-1.8 (4.29)	-0.3 (4.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.016
	Comments	[Not Specified]
	Method	ANOVA
	Comments	ANOVA model using treatment group, methotrexate use, and interaction of treatment group and methotrexate use as factors.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-2.1
	Estimation Comments	The adjusted mean difference (Apremilast-Placebo) is based on an ANOVA model described above.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.105
	Comments	[Not Specified]
	Method	ANOVA
	Comments	ANOVA model using treatment group, methotrexate use, and interaction of treatment group and methotrexate use as factors.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.4
	Estimation Comments	The adjusted mean difference (Apremilast-Placebo) is based on an ANOVA model described above.

22. Secondary Outcome

Title	Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12
Description	The HAQ-DI is a self-administered instrument consisting of 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item asks over the past week whether a particular task can be performed. For each item, there is a four-level difficulty scale that is scored from 0 to 3, representing normal (no difficulty) (0), some difficulty (1), much difficulty (2), and unable to do (3). The eight category scores are averaged into an overall HAQ-DI score on a scale from zero (no disability) to three (completely disabled).
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; participants with a baseline value and at least 1 post-baseline value in the treatment period are included; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	69	67
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.2 (0.39)	-0.2 (0.35)	-0.1 (0.39)

23. Secondary Outcome

Title	Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 12
Description	The FACIT-Fatigue is a 13 item self-administered questionnaire that assesses both the physical and functional consequences of fatigue based on recall during the past 7 days. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The total score ranges from 0 to 52 with higher scores representing less fatigue.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; participants with a baseline value and at least 1 post-baseline value in the treatment period are included; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo
Arm/Group Description:	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.
Overall Number of Participants Analyzed	67	67	64
Mean (Standard Deviation); Unit of Measure: units on a scale
	4.3 (9.46)	4.1 (8.78)	0.5 (8.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Apremilast 40 mg QD, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.028
	Comments	[Not Specified]
	Method	ANOVA
	Comments	ANOVA model with treatment, methotrexate use, and interaction of treatment group and methotrexate use as factors and baseline score as the covariate.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	3.3
	Estimation Comments	The adjusted mean difference (Apremilast-Placebo) is based on an ANOVA model described above.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Apremilast 20 mg BID, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.004
	Comments	[Not Specified]
	Method	ANOVA
	Comments	ANOVA model with treatment, methotrexate use, and interaction of treatment group and methotrexate use as factors with baseline score as the covariate.
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	4.3
	Estimation Comments	The adjusted mean difference (Apremilast-Placebo) is based on an ANOVA model described above.

24. Secondary Outcome

Title	Number of Participants With Adverse Events During the Extension Phase
Description	The severity of each adverse event (AE) was graded based upon the participant's symptoms according to National Cancer Institute (NCI) Common Toxicity Criteria (CTCAE, Version 3.0), on a scale from 1 (Mild AE) to 5 (Death due to AE). Severe AEs are defined as NCI CTCAE grade 3 or higher. AEs related to study drug are those determined by the investigator as suspected to be related to study drug where a temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other medications, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. A serious adverse event (SAE) is any AE which: - Resulted in death - Was life-threatening - Required inpatient hospitalization or prolongation of existing hospitalization - Resulted in persistent or significant disability/incapacity - Was a congenital anomaly/birth defect - Constituted an important medical event.
Time Frame	Weeks 12 to 24 (Extension Phase)

Outcome Measure Data

Analysis Population Description

The safety population; participants who entered the Extension Phase.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	46	40	20	20
Measure Type: Count of Participants; Unit of Measure: Participants
All adverse events	30 65.2%	29 72.5%	16 80.0%	11 55.0%
Adverse events related to study drug	12 26.1%	8 20.0%	4 20.0%	4 20.0%
Severe adverse events	5 10.9%	3 7.5%	3 15.0%	4 20.0%
Serious adverse events	2 4.3%	3 7.5%	1 5.0%	1 5.0%
Serious adverse events related to study drug	0 0.0%	0 0.0%	0 0.0%	1 5.0%
Discontinued study drug due to adverse event	3 6.5%	2 5.0%	0 0.0%	3 15.0%
Discontinued due to AE related to study drug	1 2.2%	1 2.5%	0 0.0%	1 5.0%

25. Secondary Outcome

Title	Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24
Description	A PsARC response is defined as improvement from Baseline in at least 2 of the following 4 measures, at least 1 of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • At least 30% improvement in the 78 tender joint count, • At least 30% improvement in the 76 swollen joint count, • At least 20% improvement in the patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • At least 20% improvement in the physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Participants with missing data were considered non-responders.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	46	40	20	20
Measure Type: Number; Unit of Measure: percentage of participants
	26.1	20.0	55.0	40.0

26. Secondary Outcome

Title	Percentage of Participants With a Modified ACR 20 Response at Week 24
Description	A modified ACR 20 response was defined as a participant who met the following 3 criteria for improvement: • ≥ 20% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm VAS); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. Response at Week 24 was measured as improvement from Baseline (Day 1) and from Week 12 (Day 85). Participants with no post-baseline ACR scores were considered non-responders.
Time Frame	Baseline (Day 1), Week 12 (Day 85) and Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase; LOCF imputation was used. For the analysis of response from Week 12 (Day 85), participants with a tender or swollen joint count of 0 at Day 85 were excluded.

Arm/Group Title		Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:		Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed		46	40	20	20
Measure Type: Number; Unit of Measure: percentage of participants
Response From Baseline	Number Analyzed	46 participants	40 participants	20 participants	20 participants
		43.5	42.5	45.0	40.0
Response From Week 12	Number Analyzed	30 participants	34 participants	13 participants	18 participants
		16.7	14.7	15.4	16.7

27. Secondary Outcome

Title	Percentage of Participants With a Modified ACR 50 Response at Week 24
Description	A modified ACR 50 response was defined as a participant who met the following 3 criteria for improvement: • ≥ 50% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm VAS); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. Response at Week 24 was measured as improvement from Baseline (Day 1) and from Week 12 (Day 85). Participants with no post-baseline ACR scores were considered non-responders.
Time Frame	Baseline (Day 1), Week 12 (Day 85) and Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase; LOCF imputation was used. For the analysis of response from Week 12 (Day 85), participants with a tender or swollen joint count of 0 at Day 85 were excluded.

Arm/Group Title		Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:		Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed		46	40	20	20
Measure Type: Number; Unit of Measure: percentage of participants
Response From Baseline	Number Analyzed	46 participants	40 participants	20 participants	20 participants
		23.9	22.5	20.0	15.0
Response From Week 12	Number Analyzed	31 participants	34 participants	13 participants	18 participants
		9.7	5.9	15.4	5.6

28. Secondary Outcome

Title	Percentage of Participants With a Modified ACR 70 Response at Week 24
Description	A modified ACR 70 response was defined as a participant who met the following 3 criteria for improvement: • ≥ 70% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm VAS); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. Response at Week 24 was measured as improvement from Baseline (Day 1). Participants with no post-baseline ACR scores were considered non-responders.
Time Frame	Baseline (Day 1) and Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	46	40	20	20
Measure Type: Number; Unit of Measure: percentage of participants
	13.0	17.5	15.0	5.0

29. Secondary Outcome

Title	Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(4) at Week 24
Description	The DAS28 measures the severity of disease at a specific time. DAS28-CRP(4) is derived from the following 4 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein • Patient's global assessment of disease activity according to the formula: DAS28-CRP(4) = 0.56*√(TJC28) + 0.28*(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96. DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity. A EULAR response reflects an improvement in disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and attainment of a DAS28 score ≤ 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	46	40	20	20
Measure Type: Number; Unit of Measure: percentage of participants
	67.4	60.0	70.0	50.0

30. Secondary Outcome

Title	Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 24
Description	The DAS28 measures the severity of disease at a specific time. DAS28-CRP(3) is derived from the following 3 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) according to the formula: DAS28-CRP(3) = [0.56*√(TJC28) + 0.28*√(SJC28) + 0.36*ln(CRP+1)] * 1.10 + 1.15. DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity. A EULAR response reflects an improvement in disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and attainment of a DAS28 score ≤ 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	46	40	20	20
Measure Type: Number; Unit of Measure: percentage of participants
	60.9	67.5	65.0	55.0

31. Secondary Outcome

Title	Maximal ACR Response During the Extension Period
Description	The ACR-N index score was calculated for each participant at each time point in the study according to the following definition: ACR-N = the lowest of the following 3 values: • percent improvement from Baseline in the 76 swollen joint count, • percent improvement from Baseline in the 78 tender joint count • median percent improvement from Baseline in the following 5 measures ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. The maximal ACR-N for each participant during the 12-week extension period was calculated, and represents the maximal ACR response achieved.
Time Frame	ACR was measured at Baseline and Weeks 16, 20 and 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase with non-missing ACR data

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	44	39	20	17
Mean (Standard Deviation); Unit of Measure: percent improvement
	29.1 (40.86)	30.4 (36.77)	23.3 (32.11)	34.2 (31.16)

32. Secondary Outcome

Title	Time to ACR 20 Response During the Study
Description	Time to ACR 20 was measured from the first dose of apremilast to the first time a participant achieved an ACR 20 response in the treatment or extension phase. The Kaplan-Meier estimates of time to ACR 20 response were calculated for participants who had an ACR 20 response at any time during the study.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase with an ACR 20 response at any time during the study

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	31	29	4	6
Median (95% Confidence Interval); Unit of Measure: days
	43.0; (29.0 to 44.0)	43.0; (29.0 to 59.0)	34.0; (29.0 to 55.0)	55.5; (29.0 to 57.0)

33. Secondary Outcome

Title	Time to ACR 50 Response During the Treatment and Extension Phase
Description	Time to ACR 50 response was measured from the first dose of apremilast to the first time a participant achieved an ACR 50 response in the treatment or extension phase. The Kaplan-Meier estimates of time to ACR 50 response were calculated for participants who had an ACR 50 response at any time during the study.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase with an ACR 50 response at any time during the study

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	18	16	2	3
Median (95% Confidence Interval); Unit of Measure: days
	71.0; (44.0 to 110.0)	58.5; (56.0 to 86.0)	84.5; (84.0 to 85.0)	55.0; (23.0 to 57.0)

34. Secondary Outcome

Title	Time to ACR 70 Response During the Treatment and Extension Phase
Description	Time to ACR 70 response was measured from the first dose of apremilast to the first time a participant achieved an ACR 70 response in the treatment or extension phase. The Kaplan-Meier estimates of time to ACR 70 response were calculated for participants who had an ACR 70 response at any time during the study.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase with an ACR 70 response at any time during the study

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	9	7	0	0
Median (95% Confidence Interval); Unit of Measure: days
	138.0; (85.0 to 169.0)	85.0; (57.0 to 141.0)

35. Secondary Outcome

Title	Change From Baseline and Week 12 in Dactylitis Severity Score at Week 24
Description	Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated on a scale from 0 (no dactylitis) to 3 (severe dactylitis). The dactylitis severity score is the sum of the individual scores for each digit and ranges from 0 to 60. Change in the dactylitis severity score was assessed from Baseline (Day 1) and from Week 12 (Day 85).
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase with a baseline/Week 12 value and at least 1 post-baseline value in the extension period; LOCF imputation was used.

Arm/Group Title		Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:		Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed		46	39	20	18
Mean (Standard Deviation); Unit of Measure: units on a scale
Change from Baseline	Number Analyzed	46 participants	39 participants	20 participants	18 participants
		-0.4 (3.47)	-1.5 (3.13)	-1.8 (4.94)	0.1 (1.08)
Change from Week 12	Number Analyzed	45 participants	39 participants	20 participants	18 participants
		0.3 (3.07)	-0.2 (1.97)	-0.3 (0.98)	-0.8 (2.39)

36. Secondary Outcome

Title	Percentage of Participants With Enthesitis in the Extension Phase
Description	Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. Enthesitis is characterized by swelling, pain, and tenderness around the calcaneous, and occasionally by effusion in the bursa associated with this joint. The enthesitis assessment is an evaluation of inflammation at the insertions of the Achilles tendon into the calcaneous and of the plantar fascia into the calcaneous. Inflammation at 1 or more insertions on either the right or left side constituted a positive assessment.
Time Frame	Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	46	40	20	20
Measure Type: Number; Unit of Measure: percentage of participants
Achilles tendon into the calcaneous: Week 12	17.4	15.0	20.0	20.0
Achilles tendon into the calcaneous: Week 24	19.6	15.0	0.0	15.0
Plantar fascia into the calcaneous:Week 12	15.2	17.5	25.0	10.0
Plantar fascia into the calcaneous: Week 24	13.0	7.5	0.0	10.0

37. Secondary Outcome

Title	Time to Relapse of Psoriatic Arthritis After Extension Phase
Description	Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Follow-up Phase in participants who achieved at least an ACR 20 at their Final Extension Phase (Week 24)/Early Termination Visit. The time to relapse during the Follow-up Phase was calculated from the time of maximum ACR reduction and from the date of the Final Extension Phase visit. Participants classified as responders who did not relapse were censored at the day of the last follow-up.
Time Frame	From Week 24 to the end of the 28-day follow-up (1) and from the date of maximal ACR until the end of the 28-day follow-up phase (2).

Outcome Measure Data

Analysis Population Description

Participants with an ACR 20 response at the Week 24 (or Early Termination) visit and entered the Follow-up Phase after the Extension Phase

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	20	17	2	3
Median (95% Confidence Interval); Unit of Measure: days
1. From Week 12	31.0 [1]; (29.0 to NA)	32.0; (29.0 to 38.0)	16.0 [1]; (NA to NA)	29.0 [1]; (15.0 to NA)
2. From Date of Maximal ACR Response	85.0 [1]; (57.0 to NA)	111 [1]; (41.0 to NA)	16.0 [1]; (NA to NA)	29.0 [1]; (15.0 to NA)

[1]

Could not be estimated due to the low number of events

38. Secondary Outcome

Title	Number of Participants Who Relapsed After the Extension Phase
Description	Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Follow-up Phase in participants who achieved at least an ACR 20 at their Final Extension Phase/Early Termination Visit.
Time Frame	Week 24 to Week 28 (28-day follow-up period)

Outcome Measure Data

Analysis Population Description

Participants with an ACR 20 response at the Week 24 (or Early Termination) visit and entered the Follow-up Phase after the Extension Phase

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	20	17	2	3
Measure Type: Number; Unit of Measure: participants
	8	8	1	2

39. Secondary Outcome

Title	Change From Baseline and Week 12 in SF-36 at Week 24
Description	The Medical Outcome SF 36-Item Health Survey, Version 2 is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The summary physical health score included the following subscales: physical functioning, role-physical, bodily pain, and general health. The summary mental health score included other subscales: vitality, social functioning, role-emotional, and mental health. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10, where higher scores are associated with better functioning/quality of life. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale. A higher change from baseline indicates an improvement in better health results or functioning.
Time Frame	Baseline (Day 1), Week 12 (Day 85) and Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase with a Baseline/Week 12 value and at least 1 post-baseline value in the extension period; LOCF imputation was used.

Arm/Group Title		Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:		Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed		43	36	20	18
Mean (Standard Deviation); Unit of Measure: units on a scale
Mental Component: Change from Baseline	Number Analyzed	41 participants	36 participants	20 participants	18 participants
		0.2 (9.08)	1.4 (8.92)	-2.7 (12.20)	-1.0 (14.00)
Mental Component: Change from Week 12	Number Analyzed	43 participants	34 participants	20 participants	18 participants
		-1.1 (8.14)	-2.4 (9.35)	-2.5 (10.60)	-3.4 (10.61)
Physical Component: Change from Baseline	Number Analyzed	41 participants	36 participants	20 participants	18 participants
		3.2 (6.68)	4.4 (7.74)	1.8 (9.50)	4.2 (9.99)
Physical Component: Change from Week 12	Number Analyzed	43 participants	34 participants	20 participants	18 participants
		0.3 (6.10)	1.0 (6.60)	-0.1 (8.50)	2.5 (7.81)

40. Secondary Outcome

Title	Change From Baseline and Week 12 in Dermatology Life Quality Index (DLQI) at Week 24
Description	The DLQI is a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on participants' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, leisure, work, personal relationships, and treatment. Each question is answered on a scale from 0 (not at all) to 3 (very much) The total score ranges from 0 to 30 where a higher score indicates that a participant's dermatological condition has a greater impact on their daily life.
Time Frame	Baseline (Day 1), Week 12 (Day 85) and Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase with a Baseline/Week 12 value and at least 1 post-baseline value in the extension period; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	43	37	20	18
Mean (Standard Deviation); Unit of Measure: units on a scale
Change from Baseline	-3.0 (7.36)	-1.5 (4.08)	-2.6 (4.78)	-1.9 (5.50)
Change from Week 12	-0.0 (5.72)	-0.1 (3.54)	-1.2 (2.07)	-2.0 (6.25)

41. Secondary Outcome

Title	Change From Baseline and Week 12 in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24
Description	The HAQ-DI is a self-administered instrument consisting of 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item asks over the past week whether a particular task can be performed. For each item, there is a four-level difficulty scale that is scored from 0 to 3, representing normal (no difficulty) (0), some difficulty (1), much difficulty (2), and unable to do (3). The eight category scores are averaged into an overall HAQ-DI score on a scale from zero (no disability) to three (completely disabled).
Time Frame	Baseline (Day 1), Week 12 (Day 85) and Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase with a Baseline/Week 12 value and at least 1 post-baseline value in the extension period; LOCF imputation was used.

Arm/Group Title		Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:		Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed		46	40	20	18
Mean (Standard Deviation); Unit of Measure: units on a scale
Change from Baseline	Number Analyzed	46 participants	40 participants	20 participants	18 participants
		-0.1 (0.45)	-0.2 (0.37)	-0.1 (0.61)	-0.2 (0.59)
Change from Week 12	Number Analyzed	46 participants	40 participants	20 participants	17 participants
		0.0 (0.37)	-0.0 (0.23)	-0.0 (0.46)	-0.2 (0.44)

42. Secondary Outcome

Title	Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 24
Description	The FACIT-Fatigue is a 13 item self-administered questionnaire that assesses both the physical and functional consequences of fatigue based on recall during the past 7 days. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The total score ranges from 0 to 52 with higher scores representing less fatigue.
Time Frame	Baseline (Day 1), Week 12 (Day 85) and Week 24

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Extension Phase with a Baseline/Week 12 value and at least 1 post-baseline value in the extension period; LOCF imputation was used.

Arm/Group Title	Apremilast 40 mg QD	Apremilast 20 mg BID	Placebo/Apremilast 40 mg QD	Placebo/Apremilast 20 mg BID
Arm/Group Description:	Participants who received apremilast 40 mg QD during the Treatment Phase continued to receive apremilast 40 mg QD for an additional 12 weeks during the Extension Phase.	Participants who received apremilast 20 mg BID during the Treatment Phase continued to receive apremilast 20 mg BID for an additional 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 40 mg apremilast orally QD for 12 weeks during the Extension Phase.	Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Overall Number of Participants Analyzed	43	37	20	18
Mean (Standard Deviation); Unit of Measure: units on a scale
Change from Baseline	4.4 (9.76)	5.9 (7.76)	1.3 (11.23)	1.3 (12.34)
Change from Week 12	-0.3 (8.56)	0.1 (6.19)	-2.4 (9.05)	-1.3 (13.10)

Adverse Events

Time Frame	Adverse events are reported for the 12-week placebo-controlled phase, including AEs that occurred during the 28-day observational follow-up, and for up to 24 weeks for all participants who were randomized or re-randomized to apremilast at any time during the study.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Week 12: Apremilast 40 mg QD	Week 12: Apremilast 20 mg BID	Week 12: Placebo	Week 24: Apremilast 40 mg QD	Week 24: Apremilast 20 mg BID
Arm/Group Description	Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Participants who received 40 mg QD apremilast, regardless of when the apremilast exposure started (at Week 0, or 12), up until Week 24.	Participants who received 20 mg apremilast BID, regardless of when the apremilast exposure started (at Week 0, 12), up until Week 24.
All-Cause Mortality
	Week 12: Apremilast 40 mg QD	Week 12: Apremilast 20 mg BID	Week 12: Placebo	Week 24: Apremilast 40 mg QD	Week 24: Apremilast 20 mg BID
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--	--/--
Serious Adverse Events
	Week 12: Apremilast 40 mg QD	Week 12: Apremilast 20 mg BID	Week 12: Placebo	Week 24: Apremilast 40 mg QD	Week 24: Apremilast 20 mg BID
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/67 (0.00%)	4/69 (5.80%)	6/68 (8.82%)	3/87 (3.45%)	8/89 (8.99%)
Cardiac disorders
Sinus tachycardia † 1	0/67 (0.00%)	1/69 (1.45%)	0/68 (0.00%)	0/87 (0.00%)	1/89 (1.12%)
Hypertensive heart disease † 1	0/67 (0.00%)	0/69 (0.00%)	0/68 (0.00%)	0/87 (0.00%)	1/89 (1.12%)
Gastrointestinal disorders
Nausea † 1	0/67 (0.00%)	0/69 (0.00%)	2/68 (2.94%)	0/87 (0.00%)	0/89 (0.00%)
Vomiting † 1	0/67 (0.00%)	0/69 (0.00%)	1/68 (1.47%)	0/87 (0.00%)	0/89 (0.00%)
Hepatobiliary disorders
Biliary colic † 1	0/67 (0.00%)	1/69 (1.45%)	0/68 (0.00%)	0/87 (0.00%)	1/89 (1.12%)
Hyperbilirubinaemia † 1	0/67 (0.00%)	1/69 (1.45%)	0/68 (0.00%)	0/87 (0.00%)	1/89 (1.12%)
Infections and infestations
Abdominal abscess † 1	0/67 (0.00%)	0/69 (0.00%)	0/68 (0.00%)	0/87 (0.00%)	1/89 (1.12%)
Wound infection † 1	0/67 (0.00%)	0/69 (0.00%)	0/68 (0.00%)	0/87 (0.00%)	1/89 (1.12%)
Injury, poisoning and procedural complications
Fall † 1	0/67 (0.00%)	0/69 (0.00%)	1/68 (1.47%)	0/87 (0.00%)	0/89 (0.00%)
Tibia fracture † 1	0/67 (0.00%)	0/69 (0.00%)	0/68 (0.00%)	1/87 (1.15%)	0/89 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/67 (0.00%)	0/69 (0.00%)	1/68 (1.47%)	0/87 (0.00%)	0/89 (0.00%)
Intervertebral disc degeneration † 1	0/67 (0.00%)	1/69 (1.45%)	0/68 (0.00%)	0/87 (0.00%)	1/89 (1.12%)
Osteoarthritis † 1	0/67 (0.00%)	0/69 (0.00%)	0/68 (0.00%)	0/87 (0.00%)	1/89 (1.12%)
Psoriatic arthropathy † 1	0/67 (0.00%)	0/69 (0.00%)	1/68 (1.47%)	0/87 (0.00%)	0/89 (0.00%)
Synovitis † 1	0/67 (0.00%)	0/69 (0.00%)	0/68 (0.00%)	0/87 (0.00%)	1/89 (1.12%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oral neoplasm † 1	0/67 (0.00%)	0/69 (0.00%)	0/68 (0.00%)	0/87 (0.00%)	1/89 (1.12%)
Squamous cell carcinoma of skin † 1	0/67 (0.00%)	0/69 (0.00%)	0/68 (0.00%)	1/87 (1.15%)	0/89 (0.00%)
Uterine leiomyoma † 1	0/67 (0.00%)	0/69 (0.00%)	1/68 (1.47%)	0/87 (0.00%)	0/89 (0.00%)
Neoplasm prostate † 1	0/67 (0.00%)	0/69 (0.00%)	0/68 (0.00%)	0/87 (0.00%)	1/89 (1.12%)
Nervous system disorders
Balance disorder † 1	0/67 (0.00%)	0/69 (0.00%)	1/68 (1.47%)	0/87 (0.00%)	0/89 (0.00%)
Parkinson's disease † 1	0/67 (0.00%)	0/69 (0.00%)	0/68 (0.00%)	1/87 (1.15%)	0/89 (0.00%)
Social circumstances
Pregnancy of partner † 1	0/67 (0.00%)	1/69 (1.45%)	0/68 (0.00%)	0/87 (0.00%)	1/89 (1.12%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 10.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Week 12: Apremilast 40 mg QD	Week 12: Apremilast 20 mg BID	Week 12: Placebo	Week 24: Apremilast 40 mg QD	Week 24: Apremilast 20 mg BID
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	45/67 (67.16%)	44/69 (63.77%)	42/68 (61.76%)	63/87 (72.41%)	62/89 (69.66%)
Gastrointestinal disorders
Diarrhoea † 1	18/67 (26.87%)	14/69 (20.29%)	7/68 (10.29%)	23/87 (26.44%)	14/89 (15.73%)
Nausea † 1	15/67 (22.39%)	12/69 (17.39%)	10/68 (14.71%)	23/87 (26.44%)	14/89 (15.73%)
Abdominal pain upper † 1	4/67 (5.97%)	7/69 (10.14%)	3/68 (4.41%)	5/87 (5.75%)	8/89 (8.99%)
Vomiting † 1	4/67 (5.97%)	4/69 (5.80%)	3/68 (4.41%)	5/87 (5.75%)	6/89 (6.74%)
Abdominal pain † 1	2/67 (2.99%)	4/69 (5.80%)	1/68 (1.47%)	2/87 (2.30%)	4/89 (4.49%)
General disorders
Fatigue † 1	11/67 (16.42%)	6/69 (8.70%)	6/68 (8.82%)	11/87 (12.64%)	7/89 (7.87%)
Infections and infestations
Nasopharyngitis † 1	8/67 (11.94%)	8/69 (11.59%)	14/68 (20.59%)	23/87 (26.44%)	18/89 (20.22%)
Upper respiratory tract infection † 1	4/67 (5.97%)	2/69 (2.90%)	0/68 (0.00%)	4/87 (4.60%)	3/89 (3.37%)
Influenza † 1	3/67 (4.48%)	0/69 (0.00%)	1/68 (1.47%)	5/87 (5.75%)	2/89 (2.25%)
Rhinitis † 1	0/67 (0.00%)	2/69 (2.90%)	0/68 (0.00%)	0/87 (0.00%)	5/89 (5.62%)
Musculoskeletal and connective tissue disorders
Psoriatic arthropathy † 1	5/67 (7.46%)	7/69 (10.14%)	8/68 (11.76%)	10/87 (11.49%)	13/89 (14.61%)
Back pain † 1	2/67 (2.99%)	1/69 (1.45%)	4/68 (5.88%)	4/87 (4.60%)	1/89 (1.12%)
Nervous system disorders
Headache † 1	15/67 (22.39%)	13/69 (18.84%)	11/68 (16.18%)	17/87 (19.54%)	17/89 (19.10%)
Dizziness † 1	7/67 (10.45%)	3/69 (4.35%)	3/68 (4.41%)	7/87 (8.05%)	3/89 (3.37%)
Migraine † 1	2/67 (2.99%)	6/69 (8.70%)	0/68 (0.00%)	3/87 (3.45%)	6/89 (6.74%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain † 1	1/67 (1.49%)	1/69 (1.45%)	4/68 (5.88%)	2/87 (2.30%)	1/89 (1.12%)
Cough † 1	0/67 (0.00%)	1/69 (1.45%)	4/68 (5.88%)	0/87 (0.00%)	3/89 (3.37%)
Skin and subcutaneous tissue disorders
Pruritus † 1	5/67 (7.46%)	2/69 (2.90%)	1/68 (1.47%)	5/87 (5.75%)	4/89 (4.49%)
Psoriasis † 1	1/67 (1.49%)	3/69 (4.35%)	3/68 (4.41%)	4/87 (4.60%)	6/89 (6.74%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 10.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 days. Investigator must delete confidential information before submission or defer publication to permit patent applications.

Results Point of Contact

• Name/Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation
• Phone: 1-888-260-1599
• EMail: clinicaltrialdisclosure@celgene.com

Publications of Results:

Strand V, Schett G, Hu C, Stevens RM. Patient-reported Health-related Quality of Life with apremilast for psoriatic arthritis: a phase II, randomized, controlled study. J Rheumatol. 2013 Jul;40(7):1158-65. doi: 10.3899/jrheum.121200. Epub 2013 Apr 15.

Other Publications:

Schett G, Wollenhaupt J, Papp K, Joos R, Rodrigues JF, Vessey AR, Hu C, Stevens R, de Vlam KL. Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2012 Oct;64(10):3156-67. doi: 10.1002/art.34627.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00456092
• Other Study ID Numbers: CC-10004-PSA-001
• First Submitted: April 2, 2007
• First Posted: April 4, 2007
• Results First Submitted: August 27, 2018
• Results First Posted: October 23, 2019
• Last Update Posted: June 19, 2020