MedPath

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

Phase 2
Completed
Conditions
Psoriatic Arthritis
Interventions
Drug: Placebo
Drug: Apremilast
Registration Number
NCT00456092
Lead Sponsor
Amgen
Brief Summary

This study is to look at the preliminary efficacy and safety of 2 dose regimens of apremilast (20 mg twice a day and 40 mg once a day) versus placebo in patients with active psoriatic arthritis.

Detailed Description

Prior to the implementation of Amendment 1/UK3 the study consisted of 3 phases - pre-randomization up to 35 days, up to 84 days placebo-controlled treatment and a 28-day observational follow up. After the implementation of Amendment 1/UK3, the study consisted of 4 phases - pre-randomization up to 35 days, up to 84 days treatment in the placebo controlled treatment phase, up to 84 days treatment in the active treatment extension phase and a 28 day follow up. Participants who completed the treatment phase prior to implementation of amendment 1/UK3 did not have the option of entering the extension phase.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
204
Inclusion Criteria

  • Diagnosis of psoriatic arthritis (Moll and Wright Criteria), including symmetrical or asymmetrical peripheral joint involvement for at least 6 months

  • Active psoriatic arthritis at the time of screening and baseline as defined by: 3 or more swollen joints AND 3 or more tender joints

  • Negative rheumatoid factor (RF)

  • If using methotrexate, be on methotrexate for at least 168 days (24 weeks) and be on a stable dose for at least 56 days prior to screening and throughout the study

  • If using oral corticosteroids, be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to screening and throughout the study

  • If using nonsteroidal anti-inflammatory drug (NSAID) therapy, be on a stable dose for at least 14 days prior to screening and throughout the study

  • Must meet the following laboratory criteria:

    • Hemoglobin ≥ 9 g/dL
    • Hematocrit ≥ 27%
    • White blood cell (WBC) count ≥ 3000/μL (≥ 3.0 X 10^9/L) and < 20,000/μL (< 20 X 10^9/L)
    • Neutrophils ≥ 1500 /μL (≥ 1.5 X 10^9/L)
    • Platelets ≥ 100,000 /μL (≥ 100 X 10^9/L)
    • Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
    • Total bilirubin ≤ 2.0 mg/dL
    • Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) ≤ 1.5x upper limit of normal (ULN)

  • Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active FCBP must agree to use TWO adequate forms of contraception while on study medication. A FCBP must agree to have pregnancy tests every 28 days while on study medication

  • Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP while on study medication and for at least 84 days after taking the last dose of study medication

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Exclusion Criteria

History of any clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major diseases

  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Pregnant or lactating female
  • History of active Mycobacterium tuberculosis infection (any subspecies) within 3 years prior to the screening visit. Infections that occurred > 3 years prior to entry must have been effectively treated.
  • History of incompletely treated latent Mycobacterium tuberculosis infection (as indicated by a positive Purified Protein Derivative [PPD] skin test or in vitro test [T SPOT®.TB, QuantiFERON Gold®])
  • Clinically significant abnormality on the chest x-ray (CXR) at screening
  • Current erythrodermic, guttate, or pustular forms of psoriasis
  • History of infected joint prosthesis within the past 5 years
  • Systemic therapy for psoriasis and/or psoriatic arthritis (except for methotrexate, ≤ 10 mg/day prednisone or equivalent, and NSAIDs) including, but not limited to, sulfasalazine, leflunomide, chloroquine, hydroxychloroquine, gold compounds, parenteral corticosteroids (including intra-articular), penicillamine, cyclosporine, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, tacrolimus, azathioprine, and fumaric acid esters within 28 days of randomization and throughout the study
  • Topical therapy for the treatment of psoriasis including, but not limited to topical steroids, topical vitamin A or D analog preparations, tacrolimus, pimecrolimus, or anthralin within 14 days of randomization (Note: Topical background therapy for treatment of psoriasis is allowed, except within 24 hours of a study visit, as follows: mild or moderate potency corticosteroids for treatment of the palms, face, scalp, axillae, plantar surfaces, and groin in accordance with the manufacturer's suggested usage. Nonmedicated emollients [eg, Eucerin®] and tar shampoo are also allowed.)
  • Phototherapy (ultraviolet light A [UVA], narrow-band ultraviolet light B [NB-UVB], psoralens and long-wave ultraviolet radiation [PUVA]) within 28 days prior to randomization
  • Etanercept use within 56 days prior to randomization
  • Adalimumab, efalizumab, or infliximab use within 84 days prior to randomization
  • Alefacept use within 168 days (24 weeks) prior to randomization
  • Use of intra-articular corticosteroids within 28 days prior to randomization
  • Use of any investigational medication within 28 days prior to randomization or 5 half-lives if known (whichever is longer)
  • Any clinically significant abnormality on 12-lead electrocardiogram (ECG) at screening
  • High-risk factor(s) for, or a history of, human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus infection
  • History of malignancy within previous 5 years (except for treated basal-cell skin carcinoma(s) and/or fewer than 3 treated squamous-cell skin carcinomas)
  • Evidence of skin conditions at the time of screening visit that would interfere with evaluations of the effect of study medication on psoriasis
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants 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.
Apremilast 40 mg QDApremilastParticipants 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 BIDApremilastParticipants 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.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With a Modified American College of Rheumatology 20% (ACR 20) Response at Week 12Baseline and Week 12

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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With a Modified ACR 50 Response at Week 12Baseline and Week 12

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.

Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 12Baseline and Week 12

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.

Percentage of Participants With DAS28-CRP(3) Score of Mild Disease Activity or In Remission at Week 12Week 12

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.

Number of Participants With Adverse Events Leading to a Dose ReductionBaseline to Week 12

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

Time to ACR 70 Response During the Treatment PhaseBaseline to Week 12

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.

Number of Participants With Adverse Events During the Treatment Phase12 weeks

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.

Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response Based on Disease Activity Score (DAS28)-CRP(4) at Week 12Baseline and Week 12

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

Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 12Baseline and Week 12

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

Percentage of Participants With DAS28-CRP(4) Score of Mild Disease Activity or In Remission at Week 12Week 12

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.

Maximal ACR Response During the Treatment PhaseACR was measured at Baseline and Weeks 2, 4, 6, 8, 10, and 12

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.

Change From Baseline in Dactylitis Severity Score at Week 12Baseline and Week 12

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.

Percentage of Participants With EnthesitisBaseline and Week 12

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.

Percentage of Participants With a Modified ACR 70 Response at Week 12Baseline and Week 12

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.

Number of Participants Who Withdrew Prematurely Due to Lack of EfficacyBaseline to Week 12

The number of participants who withdrew prematurely from the treatment phase due to lack of efficacy, including flare of psoriasis, flare of psoriatic arthritis or worsening or not responding to study treatment.

Time to ACR 50 Response During the Treatment PhaseBaseline to Week 12

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.

Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12Baseline and Week 12

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).

Number of Participants With Adverse Events During the Extension PhaseWeeks 12 to 24 (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.

Time to ACR 20 Response During the Treatment PhaseBaseline to Week 12

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.

Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(4) at Week 24Baseline and Week 24

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

Time to ACR 50 Response During the Treatment and Extension PhaseBaseline to Week 24

Time to ACR 50 response was measured from the first dose of apremilast to the first time a participant achieved an ACR 50 response in the treatment or extension phase. The Kaplan-Meier estimates of time to ACR 50 response were calculated for participants who had an ACR 50 response at any time during the study.

Time to ACR 70 Response During the Treatment and Extension PhaseBaseline to Week 24

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.

Change From Baseline and Week 12 in SF-36 at Week 24Baseline (Day 1), Week 12 (Day 85) and Week 24

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

Time to Relapse of Psoriatic Arthritis During the Observational Follow-up PhaseFrom 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).

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.

Number of Participants Who Relapsed During the Observational Follow-up Phase28-day observational follow-up period following Week 12

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.

Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 12Baseline and Week 12

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.

Change From Baseline and Week 12 in Dermatology Life Quality Index (DLQI) at Week 24Baseline (Day 1), Week 12 (Day 85) and Week 24

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.

Change From Baseline in Short Form 36 (SF-36) Summary Physical and Mental Component Scores at Week 12Baseline and Week 12

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.

Percentage of Participants With a Modified ACR 70 Response at Week 24Baseline (Day 1) and Week 24

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.

Maximal ACR Response During the Extension PeriodACR was measured at Baseline and Weeks 16, 20 and 24

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.

Percentage of Participants With Enthesitis in the Extension PhaseWeek 12 and Week 24

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.

Change From Baseline and Week 12 in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24Baseline (Day 1), Week 12 (Day 85) and Week 24

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).

Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 12Baseline and Week 12

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.

Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24Baseline and Week 24

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.

Percentage of Participants With a Modified ACR 20 Response at Week 24Baseline (Day 1), Week 12 (Day 85) and Week 24

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.

Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 24Baseline and Week 24

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

Time to ACR 20 Response During the StudyBaseline to Week 24

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

Time to Relapse of Psoriatic Arthritis After Extension PhaseFrom 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).

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.

Percentage of Participants With a Modified ACR 50 Response at Week 24Baseline (Day 1), Week 12 (Day 85) and Week 24

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.

Change From Baseline and Week 12 in Dactylitis Severity Score at Week 24Baseline, Week 12 and Week 24

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).

Number of Participants Who Relapsed After the Extension PhaseWeek 24 to Week 28 (28-day follow-up period)

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.

Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 24Baseline (Day 1), Week 12 (Day 85) and Week 24

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.

Trial Locations

Locations (37)

Chapel Allerton Hospital

🇬🇧

Leeds, United Kingdom

Freeman Hospital

🇬🇧

Newcastle-upon-Tyne, United Kingdom

Credit Valley Rheumatology

🇨🇦

Mississauga, Ontario, Canada

Capio Franz von Prümmer Klinik

🇩🇪

Bad Brückenau, Germany

Hope Hospital

🇬🇧

Salford, Manchester, United Kingdom

Haywood Hospital

🇬🇧

Stoke on Trent, Staffs, United Kingdom

Nexus Clinical Research

🇨🇦

St Johns, Newfoundland and Labrador, Canada

Jan Palfijn Ziekenhuis

🇧🇪

Merksem, Belgium

Universiteit Hasselt

🇧🇪

Diepenbeek, Belgium

Universitaetsklinikum Frankfurt

🇩🇪

Frankfurt, Germany

Universitaet Heidelberg

🇩🇪

Heidelberg, Germany

University of Munich

🇩🇪

Munich, Germany

Friedrich-Alexander University, Erlangen

🇩🇪

Nuremberg, Germany

West Island Rheumatology Research Associates

🇨🇦

Pointe-Claire, Quebec, Canada

Universitaetsklinikum Leipzig

🇩🇪

Leipzig, Germany

Klinikum der Universität Munster

🇩🇪

Munster, Germany

MAC Research Inc.

🇨🇦

Hamilton, Ontario, Canada

Center for Prognosis Studies in the Rheumatic Diseases University Health Network, Toronto Western Hospital

🇨🇦

Toronto, Ontario, Canada

Probity Medical

🇨🇦

Waterloo, Ontario, Canada

CHU Brugmann

🇧🇪

Brussels, Belgium

Clinical Research and Arthritis Centre

🇨🇦

Windsor, Ontario, Canada

The Arthritis Research Centre of Canada

🇨🇦

Vancouver, British Columbia, Canada

Mount Sinai Hospital

🇨🇦

Toronto, Ontario, Canada

Free University of Berlin

🇩🇪

Berlin, Germany

University Hospital

🇧🇪

Leuven, Belgium

K-W Musculoskeletal Research Inc.

🇨🇦

Kitchener, Ontario, Canada

Universitaetsklinik Koeln

🇩🇪

Koeln, Germany

Universitaet Leipzig

🇩🇪

Leipzig, Germany

Arthritis Program Research Group Inc

🇨🇦

Newmarket, Ontario, Canada

Klinikum Eilbek

🇩🇪

Hamburg, Germany

Rheumazentrum Ruhrgebiet

🇩🇪

Herne, Germany

Radboud University

🇳🇱

Nijmegen, Netherlands

Hagaziekenhuis

🇳🇱

Den Haag, Netherlands

Leiden University Medical Centre

🇳🇱

Leiden, Netherlands

Burlington Rheumatology and Osteoporosis Clinic

🇨🇦

Burlington, Ontario, Canada

Rheumatology Research Associates

🇨🇦

Ottawa, Ontario, Canada

Saskatoon Osteoporosis Center

🇨🇦

Saskatoon, Saskatchewan, Canada

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