Trial Outcomes & Findings for Phase II Study of Apremilast (CC-10004) in Adults With in Psoriatic Arthritis (NCT NCT00456092)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

204 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2020-06-19

Participant Flow

Participants were enrolled across 38 sites in Canada, Belgium, Germany, the Netherlands, and the United Kingdom.

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.

Participant milestones

Participant milestones
Measure	Apremilast 40 mg QD 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.	Apremilast 20 mg BID 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.	Placebo 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.	Placebo/Apremilast 40 mg QD 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.	Placebo/Apremilast 20 mg BID 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.
Extension Phase STARTED	46	40	0	20	20
Extension Phase COMPLETED	35	36	0	19	13
Extension Phase NOT COMPLETED	11	4	0	1	7
Treatment Phase (12 Weeks) STARTED	67	69	68	0	0
Treatment Phase (12 Weeks) COMPLETED	60	55	50	0	0
Treatment Phase (12 Weeks) NOT COMPLETED	7	14	18	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Apremilast 40 mg QD 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.	Apremilast 20 mg BID 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.	Placebo 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.	Placebo/Apremilast 40 mg QD 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.	Placebo/Apremilast 20 mg BID 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.
Extension Phase Grade 2 or Greater AE	2	2	0	0	2
Extension Phase Flare of Psoriatic Arthritis	1	0	0	0	1
Extension Phase Worsening / Not Responding to Study Drug	3	1	0	0	2
Extension Phase Withdrew Consent	2	0	0	0	0
Extension Phase Lost to Follow-up	1	1	0	0	1
Extension Phase Other	2	0	0	1	1
Treatment Phase (12 Weeks) Grade 2 or Greater Adverse Event (AE)	3	4	2	0	0
Treatment Phase (12 Weeks) AEs not Included in NCI Terminology	1	2	0	0	0
Treatment Phase (12 Weeks) Intolerability of the Study Drug	2	0	0	0	0
Treatment Phase (12 Weeks) Flare of Psoriasis	0	1	2	0	0
Treatment Phase (12 Weeks) Flare of Psoriatic Arthritis	0	3	3	0	0
Treatment Phase (12 Weeks) Worsening / Not Responding to Study Drug	0	2	7	0	0
Treatment Phase (12 Weeks) Withdrew Consent	0	1	2	0	0
Treatment Phase (12 Weeks) Lost to Follow-up	0	1	1	0	0
Treatment Phase (12 Weeks) Other	1	0	1	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks in the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks in the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Total n=204 Participants Total of all reporting groups
Age, Continuous	49.9 years STANDARD_DEVIATION 11.17 • n=5 Participants	50.9 years STANDARD_DEVIATION 12.58 • n=7 Participants	51.1 years STANDARD_DEVIATION 10.80 • n=5 Participants	50.6 years STANDARD_DEVIATION 11.50 • n=4 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	26 Participants n=7 Participants	36 Participants n=5 Participants	97 Participants n=4 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	43 Participants n=7 Participants	32 Participants n=5 Participants	107 Participants n=4 Participants
Race/Ethnicity, Customized White	62 Participants n=5 Participants	67 Participants n=7 Participants	68 Participants n=5 Participants	197 Participants n=4 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian/Pacific Islander	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Psoriatic Arthritis Disease Category Asymmetrical Oligoarthritis	26 Participants n=5 Participants	21 Participants n=7 Participants	20 Participants n=5 Participants	67 Participants n=4 Participants
Psoriatic Arthritis Disease Category Predominant Spondylitis	4 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Psoriatic Arthritis Disease Category Symmetric Polyarthritis	32 Participants n=5 Participants	36 Participants n=7 Participants	39 Participants n=5 Participants	107 Participants n=4 Participants
Psoriatic Arthritis Disease Category Arthritis Mutilans	2 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 Participants
Psoriatic Arthritis Disease Category Predominant Distal Interphalgeal Involvement	2 Participants n=5 Participants	9 Participants n=7 Participants	2 Participants n=5 Participants	13 Participants n=4 Participants
Psoriatic Arthritis Disease Category Missing/Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Duration of Psoriatic Arthritis	7.6 years STANDARD_DEVIATION 8.73 • n=5 Participants	8.4 years STANDARD_DEVIATION 9.77 • n=7 Participants	7.3 years STANDARD_DEVIATION 6.74 • n=5 Participants	7.8 years STANDARD_DEVIATION 8.48 • n=4 Participants
Pain/Tender Joint Score	23.2 joints STANDARD_DEVIATION 17.63 • n=5 Participants	20.6 joints STANDARD_DEVIATION 15.90 • n=7 Participants	21.3 joints STANDARD_DEVIATION 15.55 • n=5 Participants	21.7 joints STANDARD_DEVIATION 16.33 • n=4 Participants
Swollen Joint Score	8.4 joints STANDARD_DEVIATION 4.94 • n=5 Participants	10.6 joints STANDARD_DEVIATION 9.88 • n=7 Participants	9.5 joints STANDARD_DEVIATION 9.68 • n=5 Participants	9.5 joints STANDARD_DEVIATION 8.51 • n=4 Participants
Psoriasis Severity None	2 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants	21 Participants n=4 Participants
Psoriasis Severity Mild	41 Participants n=5 Participants	47 Participants n=7 Participants	40 Participants n=5 Participants	128 Participants n=4 Participants
Psoriasis Severity Moderate	20 Participants n=5 Participants	15 Participants n=7 Participants	11 Participants n=5 Participants	46 Participants n=4 Participants
Psoriasis Severity Severe	4 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=4 Participants
Duration of Psoriasis	18.3 years STANDARD_DEVIATION 13.62 • n=5 Participants	15.5 years STANDARD_DEVIATION 11.66 • n=7 Participants	15.8 years STANDARD_DEVIATION 13.22 • n=5 Participants	16.5 years STANDARD_DEVIATION 12.85 • n=4 Participants
Methotrexate Use Yes	30 Participants n=5 Participants	30 Participants n=7 Participants	29 Participants n=5 Participants	89 Participants n=4 Participants
Methotrexate Use No	37 Participants n=5 Participants	39 Participants n=7 Participants	39 Participants n=5 Participants	115 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With a Modified American College of Rheumatology 20% (ACR 20) Response at Week 12	35.8 percentage of participants	43.5 percentage of participants	11.8 percentage of participants	—

SECONDARY outcome

Timeframe: 12 weeks

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Number of Participants With Adverse Events During the Treatment Phase All adverse events	58 Participants	59 Participants	55 Participants	—
Number of Participants With Adverse Events During the Treatment Phase Adverse events related to study drug	27 Participants	26 Participants	26 Participants	—
Number of Participants With Adverse Events During the Treatment Phase Severe adverse events	5 Participants	4 Participants	6 Participants	—
Number of Participants With Adverse Events During the Treatment Phase Severe adverse events related to study drug	1 Participants	1 Participants	1 Participants	—
Number of Participants With Adverse Events During the Treatment Phase Serious adverse events	0 Participants	4 Participants	4 Participants	—
Number of Participants With Adverse Events During the Treatment Phase Serious adverse events related to study drug	0 Participants	0 Participants	1 Participants	—
Number of Participants With Adverse Events During the Treatment Phase Discontinued study drug due to adverse event	6 Participants	10 Participants	7 Participants	—
Number of Participants With Adverse Events During the Treatment Phase Discontinued due to AE related to study drug	5 Participants	4 Participants	1 Participants	—

SECONDARY outcome

Timeframe: Baseline and Week 12

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 12	50.7 percentage of participants	52.2 percentage of participants	22.1 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 12

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With a Modified ACR 50 Response at Week 12	13.4 percentage of participants	17.4 percentage of participants	2.9 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 12

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With a Modified ACR 70 Response at Week 12	7.5 percentage of participants	5.8 percentage of participants	1.5 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 12

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

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

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response Based on Disease Activity Score (DAS28)-CRP(4) at Week 12	49.3 percentage of participants	55.1 percentage of participants	38.2 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 12

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

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

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 12	50.7 percentage of participants	44.9 percentage of participants	44.1 percentage of participants	—

SECONDARY outcome

Timeframe: Week 12

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With DAS28-CRP(4) Score of Mild Disease Activity or In Remission at Week 12	38.8 percentage of participants	33.3 percentage of participants	23.5 percentage of participants	—

SECONDARY outcome

Timeframe: Week 12

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With DAS28-CRP(3) Score of Mild Disease Activity or In Remission at Week 12	40.3 percentage of participants	34.8 percentage of participants	33.8 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Intent-to-treat population

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Number of Participants Who Withdrew Prematurely Due to Lack of Efficacy	0 Participants	6 Participants	12 Participants	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Safety population

The number of participants who were dose reduced during the treatment phase due to adverse events.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Number of Participants With Adverse Events Leading to a Dose Reduction	4 Participants	4 Participants	0 Participants	—

SECONDARY outcome

Timeframe: ACR was measured at Baseline and Weeks 2, 4, 6, 8, 10, and 12

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=65 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=67 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=65 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Maximal ACR Response During the Treatment Phase	22.3 percent improvement Standard Deviation 56.45	24.2 percent improvement Standard Deviation 37.63	10.7 percent improvement Standard Deviation 35.42	—

SECONDARY outcome

Timeframe: Baseline to Week 12

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=37 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=43 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=31 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Time to ACR 20 Response During the Treatment Phase	29.0 days Interval 29.0 to 43.0	30.0 days Interval 29.0 to 57.0	29.0 days Interval 20.0 to 47.0	—

SECONDARY outcome

Timeframe: Baseline to Week 12

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=17 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=18 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=5 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Time to ACR 50 Response During the Treatment Phase	43.0 days Interval 29.0 to 61.0	57.5 days Interval 56.0 to 72.0	15.0 days Interval 14.0 to 73.0	—

SECONDARY outcome

Timeframe: Baseline to Week 12

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=7 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=5 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=2 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Time to ACR 70 Response During the Treatment Phase	62.0 days Interval 47.0 to 85.0	57.0 days Interval 43.0 to 85.0	58.0 days Interval 31.0 to 85.0	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=67 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=67 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Change From Baseline in Dactylitis Severity Score at Week 12	-0.9 units on a scale Standard Deviation 2.39	-1.2 units on a scale Standard Deviation 3.11	-0.2 units on a scale Standard Deviation 3.75	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-treat population

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=68 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With Enthesitis Achilles tendon into the calcaneous: Baseline	22.4 percentage of participants	21.7 percentage of participants	35.3 percentage of participants	—
Percentage of Participants With Enthesitis Achilles tendon into the calcaneous: Week 12	20.9 percentage of participants	17.4 percentage of participants	17.6 percentage of participants	—
Percentage of Participants With Enthesitis Plantar fascia into the calcaneous: Baseline	26.9 percentage of participants	26.1 percentage of participants	14.7 percentage of participants	—
Percentage of Participants With Enthesitis Plantar fascia into the calcaneous: Week 12	19.4 percentage of participants	21.7 percentage of participants	17.6 percentage of participants	—

SECONDARY outcome

Timeframe: 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).

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=7 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=11 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Time to Relapse of Psoriatic Arthritis During the Observational Follow-up Phase 1. From Week 12	16.0 days Interval 15.0 to 29.0	15.0 days Interval 14.0 to 29.0	—	—
Time to Relapse of Psoriatic Arthritis During the Observational Follow-up Phase 2. From Date of Maximal ACR Response	43.0 days Interval 34.0 to 73.0	29.0 days Interval 22.0 to 43.0	—	—

SECONDARY outcome

Timeframe: 28-day observational follow-up period following Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=7 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=11 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Number of Participants Who Relapsed During the Observational Follow-up Phase	5 Participants	9 Participants	—	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=65 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=64 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=61 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Change From Baseline in Short Form 36 (SF-36) Summary Physical and Mental Component Scores at Week 12 Mental Component	1.0 units on a scale Standard Deviation 8.01	3.4 units on a scale Standard Deviation 7.18	-0.8 units on a scale Standard Deviation 8.39	—
Change From Baseline in Short Form 36 (SF-36) Summary Physical and Mental Component Scores at Week 12 Physical Component	2.1 units on a scale Standard Deviation 5.94	2.4 units on a scale Standard Deviation 7.89	0.8 units on a scale Standard Deviation 6.24	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=67 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=64 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 12	-2.6 units on a scale Standard Deviation 5.96	-1.8 units on a scale Standard Deviation 4.29	-0.3 units on a scale Standard Deviation 4.82	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=69 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=67 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12	-0.2 units on a scale Standard Deviation 0.39	-0.2 units on a scale Standard Deviation 0.35	-0.1 units on a scale Standard Deviation 0.39	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=67 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=67 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=64 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 12	4.3 units on a scale Standard Deviation 9.46	4.1 units on a scale Standard Deviation 8.78	0.5 units on a scale Standard Deviation 8.03	—

SECONDARY outcome

Timeframe: Weeks 12 to 24 (Extension Phase)

Population: The safety population; participants who entered the Extension Phase.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=46 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=40 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=20 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Number of Participants With Adverse Events During the Extension Phase All adverse events	30 Participants	29 Participants	16 Participants	11 Participants
Number of Participants With Adverse Events During the Extension Phase Adverse events related to study drug	12 Participants	8 Participants	4 Participants	4 Participants
Number of Participants With Adverse Events During the Extension Phase Severe adverse events	5 Participants	3 Participants	3 Participants	4 Participants
Number of Participants With Adverse Events During the Extension Phase Serious adverse events	2 Participants	3 Participants	1 Participants	1 Participants
Number of Participants With Adverse Events During the Extension Phase Serious adverse events related to study drug	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Adverse Events During the Extension Phase Discontinued study drug due to adverse event	3 Participants	2 Participants	0 Participants	3 Participants
Number of Participants With Adverse Events During the Extension Phase Discontinued due to AE related to study drug	1 Participants	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and Week 24

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=46 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=40 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=20 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24	26.1 percentage of participants	20.0 percentage of participants	55.0 percentage of participants	40.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1), Week 12 (Day 85) and Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=46 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=40 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=20 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With a Modified ACR 20 Response at Week 24 Response From Baseline	43.5 percentage of participants	42.5 percentage of participants	45.0 percentage of participants	40.0 percentage of participants
Percentage of Participants With a Modified ACR 20 Response at Week 24 Response From Week 12	16.7 percentage of participants	14.7 percentage of participants	15.4 percentage of participants	16.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1), Week 12 (Day 85) and Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=46 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=40 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=20 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With a Modified ACR 50 Response at Week 24 Response From Baseline	23.9 percentage of participants	22.5 percentage of participants	20.0 percentage of participants	15.0 percentage of participants
Percentage of Participants With a Modified ACR 50 Response at Week 24 Response From Week 12	9.7 percentage of participants	5.9 percentage of participants	15.4 percentage of participants	5.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=46 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=40 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=20 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With a Modified ACR 70 Response at Week 24	13.0 percentage of participants	17.5 percentage of participants	15.0 percentage of participants	5.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

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

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

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=46 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=40 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=20 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(4) at Week 24	67.4 percentage of participants	60.0 percentage of participants	70.0 percentage of participants	50.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

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

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

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=46 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=40 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=20 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 24	60.9 percentage of participants	67.5 percentage of participants	65.0 percentage of participants	55.0 percentage of participants

SECONDARY outcome

Timeframe: ACR was measured at Baseline and Weeks 16, 20 and 24

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=44 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=39 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=17 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Maximal ACR Response During the Extension Period	29.1 percent improvement Standard Deviation 40.86	30.4 percent improvement Standard Deviation 36.77	23.3 percent improvement Standard Deviation 32.11	34.2 percent improvement Standard Deviation 31.16

SECONDARY outcome

Timeframe: Baseline to Week 24

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=31 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=29 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=4 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=6 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Time to ACR 20 Response During the Study	43.0 days Interval 29.0 to 44.0	43.0 days Interval 29.0 to 59.0	34.0 days Interval 29.0 to 55.0	55.5 days Interval 29.0 to 57.0

SECONDARY outcome

Timeframe: Baseline to Week 24

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=18 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=16 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=2 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=3 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Time to ACR 50 Response During the Treatment and Extension Phase	71.0 days Interval 44.0 to 110.0	58.5 days Interval 56.0 to 86.0	84.5 days Interval 84.0 to 85.0	55.0 days Interval 23.0 to 57.0

SECONDARY outcome

Timeframe: Baseline to Week 24

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=9 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=7 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Time to ACR 70 Response During the Treatment and Extension Phase	138.0 days Interval 85.0 to 169.0	85.0 days Interval 57.0 to 141.0	—	—

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=46 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=39 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=18 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Change From Baseline and Week 12 in Dactylitis Severity Score at Week 24 Change from Baseline	-0.4 units on a scale Standard Deviation 3.47	-1.5 units on a scale Standard Deviation 3.13	-1.8 units on a scale Standard Deviation 4.94	0.1 units on a scale Standard Deviation 1.08
Change From Baseline and Week 12 in Dactylitis Severity Score at Week 24 Change from Week 12	0.3 units on a scale Standard Deviation 3.07	-0.2 units on a scale Standard Deviation 1.97	-0.3 units on a scale Standard Deviation 0.98	-0.8 units on a scale Standard Deviation 2.39

SECONDARY outcome

Timeframe: Week 12 and Week 24

Population: Participants enrolled in the Extension Phase

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=46 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=40 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=20 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Percentage of Participants With Enthesitis in the Extension Phase Plantar fascia into the calcaneous: Week 24	13.0 percentage of participants	7.5 percentage of participants	0.0 percentage of participants	10.0 percentage of participants
Percentage of Participants With Enthesitis in the Extension Phase Achilles tendon into the calcaneous: Week 12	17.4 percentage of participants	15.0 percentage of participants	20.0 percentage of participants	20.0 percentage of participants
Percentage of Participants With Enthesitis in the Extension Phase Achilles tendon into the calcaneous: Week 24	19.6 percentage of participants	15.0 percentage of participants	0.0 percentage of participants	15.0 percentage of participants
Percentage of Participants With Enthesitis in the Extension Phase Plantar fascia into the calcaneous:Week 12	15.2 percentage of participants	17.5 percentage of participants	25.0 percentage of participants	10.0 percentage of participants

SECONDARY outcome

Timeframe: 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).

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=20 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=17 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=2 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=3 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Time to Relapse of Psoriatic Arthritis After Extension Phase 1. From Week 12	31.0 days Interval 29.0 to Could not be estimated due to the low number of events	32.0 days Interval 29.0 to 38.0	16.0 days Could not be estimated due to the low number of events	29.0 days Interval 15.0 to Could not be estimated due to the low number of events
Time to Relapse of Psoriatic Arthritis After Extension Phase 2. From Date of Maximal ACR Response	85.0 days Interval 57.0 to Could not be estimated due to the low number of events	111 days Interval 41.0 to Could not be estimated due to the low number of events	16.0 days Could not be estimated due to the low number of events	29.0 days Interval 15.0 to Could not be estimated due to the low number of events

SECONDARY outcome

Timeframe: Week 24 to Week 28 (28-day follow-up period)

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

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=20 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=17 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=2 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=3 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Number of Participants Who Relapsed After the Extension Phase	8 participants	8 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: Baseline (Day 1), Week 12 (Day 85) and Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=43 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=36 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=18 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Change From Baseline and Week 12 in SF-36 at Week 24 Mental Component: Change from Baseline	0.2 units on a scale Standard Deviation 9.08	1.4 units on a scale Standard Deviation 8.92	-2.7 units on a scale Standard Deviation 12.20	-1.0 units on a scale Standard Deviation 14.00
Change From Baseline and Week 12 in SF-36 at Week 24 Mental Component: Change from Week 12	-1.1 units on a scale Standard Deviation 8.14	-2.4 units on a scale Standard Deviation 9.35	-2.5 units on a scale Standard Deviation 10.60	-3.4 units on a scale Standard Deviation 10.61
Change From Baseline and Week 12 in SF-36 at Week 24 Physical Component: Change from Baseline	3.2 units on a scale Standard Deviation 6.68	4.4 units on a scale Standard Deviation 7.74	1.8 units on a scale Standard Deviation 9.50	4.2 units on a scale Standard Deviation 9.99
Change From Baseline and Week 12 in SF-36 at Week 24 Physical Component: Change from Week 12	0.3 units on a scale Standard Deviation 6.10	1.0 units on a scale Standard Deviation 6.60	-0.1 units on a scale Standard Deviation 8.50	2.5 units on a scale Standard Deviation 7.81

SECONDARY outcome

Timeframe: Baseline (Day 1), Week 12 (Day 85) and Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=43 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=37 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=18 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Change From Baseline and Week 12 in Dermatology Life Quality Index (DLQI) at Week 24 Change from Baseline	-3.0 units on a scale Standard Deviation 7.36	-1.5 units on a scale Standard Deviation 4.08	-2.6 units on a scale Standard Deviation 4.78	-1.9 units on a scale Standard Deviation 5.50
Change From Baseline and Week 12 in Dermatology Life Quality Index (DLQI) at Week 24 Change from Week 12	-0.0 units on a scale Standard Deviation 5.72	-0.1 units on a scale Standard Deviation 3.54	-1.2 units on a scale Standard Deviation 2.07	-2.0 units on a scale Standard Deviation 6.25

SECONDARY outcome

Timeframe: Baseline (Day 1), Week 12 (Day 85) and Week 24

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=46 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=40 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=18 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Change From Baseline and Week 12 in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 Change from Baseline	-0.1 units on a scale Standard Deviation 0.45	-0.2 units on a scale Standard Deviation 0.37	-0.1 units on a scale Standard Deviation 0.61	-0.2 units on a scale Standard Deviation 0.59
Change From Baseline and Week 12 in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 Change from Week 12	0.0 units on a scale Standard Deviation 0.37	-0.0 units on a scale Standard Deviation 0.23	-0.0 units on a scale Standard Deviation 0.46	-0.2 units on a scale Standard Deviation 0.44

SECONDARY outcome

Timeframe: Baseline (Day 1), Week 12 (Day 85) and Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Apremilast 40 mg QD n=43 Participants Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Apremilast 20 mg BID n=37 Participants Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Placebo n=20 Participants Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Placebo/Apremilast 20 mg BID n=18 Participants Participants who received placebo during the Treatment Phase then received 20 mg apremilast orally BID for 12 weeks during the Extension Phase.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 24 Change from Baseline	4.4 units on a scale Standard Deviation 9.76	5.9 units on a scale Standard Deviation 7.76	1.3 units on a scale Standard Deviation 11.23	1.3 units on a scale Standard Deviation 12.34
Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 24 Change from Week 12	-0.3 units on a scale Standard Deviation 8.56	0.1 units on a scale Standard Deviation 6.19	-2.4 units on a scale Standard Deviation 9.05	-1.3 units on a scale Standard Deviation 13.10

Adverse Events

Week 12: Apremilast 40 mg QD

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

Week 12: Apremilast 20 mg BID

Serious events: 4 serious events

Other events: 44 other events

Deaths: 0 deaths

Week 12: Placebo

Serious events: 6 serious events

Other events: 42 other events

Deaths: 0 deaths

Week 24: Apremilast 40 mg QD

Serious events: 3 serious events

Other events: 63 other events

Deaths: 0 deaths

Week 24: Apremilast 20 mg BID

Serious events: 8 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Week 12: Apremilast 40 mg QD n=67 participants at risk Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Week 12: Apremilast 20 mg BID n=69 participants at risk Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Week 12: Placebo n=68 participants at risk Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Week 24: Apremilast 40 mg QD n=87 participants at risk Participants who received 40 mg QD apremilast, regardless of when the apremilast exposure started (at Week 0, or 12), up until Week 24.	Week 24: Apremilast 20 mg BID n=89 participants at risk Participants who received 20 mg apremilast BID, regardless of when the apremilast exposure started (at Week 0, 12), up until Week 24.
Hepatobiliary disorders Biliary colic	0.00% 0/67 • 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.	1.4% 1/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	1.1% 1/89 • 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.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/67 • 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.	1.4% 1/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	1.1% 1/89 • 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.
Gastrointestinal disorders Nausea	0.00% 0/67 • 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.	0.00% 0/69 • 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.	2.9% 2/68 • 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.	0.00% 0/87 • 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.	0.00% 0/89 • 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.
Gastrointestinal disorders Vomiting	0.00% 0/67 • 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.	0.00% 0/69 • 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.	1.5% 1/68 • 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.	0.00% 0/87 • 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.	0.00% 0/89 • 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.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/67 • 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.	0.00% 0/69 • 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.	1.5% 1/68 • 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.	0.00% 0/87 • 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.	0.00% 0/89 • 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.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.00% 0/67 • 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.	1.4% 1/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	1.1% 1/89 • 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.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/67 • 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.	0.00% 0/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	1.1% 1/89 • 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.
Musculoskeletal and connective tissue disorders Psoriatic arthropathy	0.00% 0/67 • 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.	0.00% 0/69 • 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.	1.5% 1/68 • 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.	0.00% 0/87 • 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.	0.00% 0/89 • 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.
Musculoskeletal and connective tissue disorders Synovitis	0.00% 0/67 • 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.	0.00% 0/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	1.1% 1/89 • 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.
Cardiac disorders Sinus tachycardia	0.00% 0/67 • 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.	1.4% 1/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	1.1% 1/89 • 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.
Cardiac disorders Hypertensive heart disease	0.00% 0/67 • 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.	0.00% 0/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	1.1% 1/89 • 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.
Injury, poisoning and procedural complications Fall	0.00% 0/67 • 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.	0.00% 0/69 • 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.	1.5% 1/68 • 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.	0.00% 0/87 • 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.	0.00% 0/89 • 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.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/67 • 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.	0.00% 0/69 • 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.	0.00% 0/68 • 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.	1.1% 1/87 • 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.	0.00% 0/89 • 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.
Nervous system disorders Balance disorder	0.00% 0/67 • 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.	0.00% 0/69 • 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.	1.5% 1/68 • 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.	0.00% 0/87 • 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.	0.00% 0/89 • 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.
Nervous system disorders Parkinson's disease	0.00% 0/67 • 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.	0.00% 0/69 • 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.	0.00% 0/68 • 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.	1.1% 1/87 • 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.	0.00% 0/89 • 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.
Social circumstances Pregnancy of partner	0.00% 0/67 • 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.	1.4% 1/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	1.1% 1/89 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oral neoplasm	0.00% 0/67 • 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.	0.00% 0/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	1.1% 1/89 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/67 • 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.	0.00% 0/69 • 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.	0.00% 0/68 • 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.	1.1% 1/87 • 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.	0.00% 0/89 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/67 • 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.	0.00% 0/69 • 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.	1.5% 1/68 • 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.	0.00% 0/87 • 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.	0.00% 0/89 • 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.
Infections and infestations Abdominal abscess	0.00% 0/67 • 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.	0.00% 0/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	1.1% 1/89 • 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.
Infections and infestations Wound infection	0.00% 0/67 • 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.	0.00% 0/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	1.1% 1/89 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm prostate	0.00% 0/67 • 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.	0.00% 0/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	1.1% 1/89 • 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.

Other adverse events

Other adverse events
Measure	Week 12: Apremilast 40 mg QD n=67 participants at risk Participants received 40 mg apremilast once daily (QD) for 12 weeks during the Treatment Phase.	Week 12: Apremilast 20 mg BID n=69 participants at risk Participants received 20 mg apremilast twice a day (BID) for 12 weeks during the Treatment Phase.	Week 12: Placebo n=68 participants at risk Participants received matching placebo to apremilast for 12 weeks during the Treatment Phase.	Week 24: Apremilast 40 mg QD n=87 participants at risk Participants who received 40 mg QD apremilast, regardless of when the apremilast exposure started (at Week 0, or 12), up until Week 24.	Week 24: Apremilast 20 mg BID n=89 participants at risk Participants who received 20 mg apremilast BID, regardless of when the apremilast exposure started (at Week 0, 12), up until Week 24.
Infections and infestations Nasopharyngitis	11.9% 8/67 • 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.	11.6% 8/69 • 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.	20.6% 14/68 • 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.	26.4% 23/87 • 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.	20.2% 18/89 • 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.
Infections and infestations Upper respiratory tract infection	6.0% 4/67 • 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.	2.9% 2/69 • 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.	0.00% 0/68 • 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.	4.6% 4/87 • 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.	3.4% 3/89 • 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.
Infections and infestations Influenza	4.5% 3/67 • 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.	0.00% 0/69 • 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.	1.5% 1/68 • 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.	5.7% 5/87 • 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.	2.2% 2/89 • 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.
Infections and infestations Rhinitis	0.00% 0/67 • 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.	2.9% 2/69 • 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.	0.00% 0/68 • 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.	0.00% 0/87 • 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.	5.6% 5/89 • 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.
Nervous system disorders Headache	22.4% 15/67 • 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.	18.8% 13/69 • 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.	16.2% 11/68 • 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.	19.5% 17/87 • 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.	19.1% 17/89 • 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.
Nervous system disorders Dizziness	10.4% 7/67 • 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.	4.3% 3/69 • 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.	4.4% 3/68 • 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.	8.0% 7/87 • 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.	3.4% 3/89 • 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.
Nervous system disorders Migraine	3.0% 2/67 • 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.	8.7% 6/69 • 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.	0.00% 0/68 • 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.	3.4% 3/87 • 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.	6.7% 6/89 • 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.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.5% 1/67 • 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.	1.4% 1/69 • 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.	5.9% 4/68 • 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.	2.3% 2/87 • 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.	1.1% 1/89 • 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.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/67 • 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.	1.4% 1/69 • 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.	5.9% 4/68 • 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.	0.00% 0/87 • 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.	3.4% 3/89 • 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.
Gastrointestinal disorders Diarrhoea	26.9% 18/67 • 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.	20.3% 14/69 • 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.	10.3% 7/68 • 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.	26.4% 23/87 • 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.	15.7% 14/89 • 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.
Gastrointestinal disorders Nausea	22.4% 15/67 • 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.	17.4% 12/69 • 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.	14.7% 10/68 • 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.	26.4% 23/87 • 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.	15.7% 14/89 • 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.
Gastrointestinal disorders Abdominal pain upper	6.0% 4/67 • 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.	10.1% 7/69 • 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.	4.4% 3/68 • 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.	5.7% 5/87 • 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.	9.0% 8/89 • 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.
Gastrointestinal disorders Vomiting	6.0% 4/67 • 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.	5.8% 4/69 • 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.	4.4% 3/68 • 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.	5.7% 5/87 • 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.	6.7% 6/89 • 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.
Gastrointestinal disorders Abdominal pain	3.0% 2/67 • 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.	5.8% 4/69 • 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.	1.5% 1/68 • 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.	2.3% 2/87 • 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.	4.5% 4/89 • 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.
Skin and subcutaneous tissue disorders Pruritus	7.5% 5/67 • 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.	2.9% 2/69 • 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.	1.5% 1/68 • 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.	5.7% 5/87 • 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.	4.5% 4/89 • 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.
Skin and subcutaneous tissue disorders Psoriasis	1.5% 1/67 • 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.	4.3% 3/69 • 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.	4.4% 3/68 • 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.	4.6% 4/87 • 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.	6.7% 6/89 • 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.
Musculoskeletal and connective tissue disorders Psoriatic arthropathy	7.5% 5/67 • 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.	10.1% 7/69 • 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.	11.8% 8/68 • 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.	11.5% 10/87 • 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.	14.6% 13/89 • 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.
Musculoskeletal and connective tissue disorders Back pain	3.0% 2/67 • 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.	1.4% 1/69 • 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.	5.9% 4/68 • 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.	4.6% 4/87 • 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.	1.1% 1/89 • 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.
General disorders Fatigue	16.4% 11/67 • 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.	8.7% 6/69 • 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.	8.8% 6/68 • 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.	12.6% 11/87 • 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.	7.9% 7/89 • 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.

Additional Information

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