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Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis (PsA) (PALACE4)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01307423
Recruitment Status : Completed
First Posted : March 2, 2011
Results First Posted : August 15, 2014
Last Update Posted : May 6, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Psoriatic Arthritis
Interventions Drug: Apremilast 20mg
Drug: Apremilast 30mg
Drug: Placebo
Enrollment 529
Recruitment Details The study was conducted in 16 countries including the United States, Canada, Europe, New Zealand, Australia and Russia.
Pre-assignment Details This study consisted of a 24-week randomized, double-blind, placebo-controlled phase, a 28-week randomized, double-blind active treatment phase and a 4-year open-label safety phase, for an overall study duration of 5 years.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg Placebo/ Apremilast 20 mg EE Placebo / Apremilast 20 mg XO Placebo / Apremilast 30 mg EE Placebo / Apremilast 30 mg XO Placebo/Apremilast 20 mg [Long-Term Safety Phase (LTSP)] Placebo/Apremilast 30 mg (Long-Term Safety Phase)
Hide Arm/Group Description Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape). Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase and continued to receive 20 mg apremilast tablets twice daily for up to 4.5 years in the active treatment / long-term safety phase. Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase and continued to receive 30 mg apremilast tablets twice daily for up to 4.5 years in the active treatment / long-term safety phase. Participants initially randomized to receive placebo twice daily who were re-randomized due to early escape (EE) at Week 16 to receive 20 mg apremilast twice daily in the active treatment phase. Participants initially randomized to receive placebo twice daily who were re-randomized at Week 24 (XO) to receive 20 mg apremilast twice daily in the active treatment phase. Participants initially randomized to receive placebo twice daily who were re-randomized due to early escape (EE) at Week 16 to receive 30 mg apremilast twice daily in the active treatment phase. Participants initially randomized to receive placebo twice daily who were re-randomized at Week 24 to receive 30 mg apremilast twice daily in the active treatment phase. Participants initially randomized to placebo tablets twice daily during the 24-week placebo-controlled phase were re-randomized to 20 mg apremilast tablets twice daily at Week 16 or Week 24 and continued receiving apremilast 20 mg tablets twice daily in active treatment / long-term safety phase. (After 30 mg apremilast BID was identified as the optimal dose, all participants receiving 20 mg apremilast BID were switched to the 30 mg apremilast BID dose). Participants initially randomized to placebo tablets BID during the 24-week placebo-controlled phase were re-randomized to apremilast 30 mg tablets twice daily at Week 16 or Week 24 and continued receiving apremilast 30 mg tablets twice daily in the active treatment / long-term safety phase.
Period Title: Placebo-controlled Phase (Week 0 - 24)
Started 176 175 177 0 0 0 0 0 0
Received Treatment 176 175 175 0 0 0 0 0 0
Completed Week 16 166 168 166 0 0 0 0 0 0
Early Escape at Week 16 103 [1] 73 79 0 0 0 0 0 0
Completed 156 [2] 160 155 0 0 0 0 0 0
Not Completed 20 15 22 0 0 0 0 0 0
Reason Not Completed
Adverse Event             4             4             6             0             0             0             0             0             0
Lack of Efficacy             1             3             2             0             0             0             0             0             0
Withdrawal by Subject             8             4             10             0             0             0             0             0             0
Randomization Error             0             0             1             0             0             0             0             0             0
Lost to Follow-up             5             1             2             0             0             0             0             0             0
Protocol Violation             1             0             0             0             0             0             0             0             0
Other             1             2             0             0             0             0             0             0             0
Non-compliance with Study Drug             0             1             1             0             0             0             0             0             0
[1]
One participant who escaped early did not complete Week 24
[2]
Two participants did not escape early and finished Week 24 did not enter the active treatment phase
Period Title: Active Treatment Phase (Week 25-52)
Started 0 151 [1] 150 [2] 46 [3] 26 46 [4] 26 0 0
Completed 0 132 141 38 23 43 25 0 0
Not Completed 0 19 9 8 3 3 1 0 0
Reason Not Completed
Adverse Event             0             3             2             2             2             0             0             0             0
Lack of Efficacy             0             5             5             3             1             0             0             0             0
Non-compliance with Study Drug             0             0             0             0             0             1             0             0             0
Withdrawal by Subject             0             11             2             0             0             1             1             0             0
Lost to Follow-up             0             0             0             2             0             0             0             0             0
Other             0             0             0             1             0             0             0             0             0
Protocol Violation             0             0             0             0             0             1             0             0             0
[1]
Nine participants who completed Week 24 did not enter active treatment phase
[2]
Five participants who completed Week 24 did not enter active treatment phase
[3]
Four participants who escaped early and completed Week 24 did not enter the active treatment phase.
[4]
Six participants who escaped early and completed Week 24 did not enter the active treatment phase
Period Title: Long-term Safety Phase (Year 2)
Started 0 122 [1] 134 [2] 0 0 0 0 57 [3] 67 [4]
Completed 0 99 109 0 0 0 0 48 60
Not Completed 0 23 25 0 0 0 0 9 7
Reason Not Completed
Adverse Event             0             2             7             0             0             0             0             1             1
Lack of Efficacy             0             7             5             0             0             0             0             4             3
Noncompliance with study drug             0             0             1             0             0             0             0             0             0
Withdrawal by Subject             0             13             12             0             0             0             0             3             2
Miscellaneous             0             1             0             0             0             0             0             1             1
[1]
10 participants who completed Week 52 did not enter the long-term safety phase
[2]
7 participants who completed Week 52 did not enter the long-term safety phase
[3]
Patients from the PBO/APR 20 mg EE and XO are combined;15 patients finished Wk 52;no entry into LTSP
[4]
Patients from the PBO/APR 30 mg EE and XO are combined;5 patients finished Wk 52;no entry into LTSP
Period Title: Long-term Safety Phase (Year 3)
Started [1] 0 99 109 0 0 0 0 48 60
Completed 0 90 91 0 0 0 0 40 49
Not Completed 0 9 18 0 0 0 0 8 11
Reason Not Completed
Adverse Event             0             1             2             0             0             0             0             3             4
Lack of Efficacy             0             2             4             0             0             0             0             1             2
Noncompliance with Study Drug             0             1             1             0             0             0             0             0             0
Withdrawal by Subject             0             2             8             0             0             0             0             2             4
Lost to Follow-up             0             2             3             0             0             0             0             1             1
Miscellaneous             0             1             0             0             0             0             0             1             0
[1]
The PBO/APR 20 mg and 30 mg EE and XO patients from week 24-52 are combined within the LTSP
Period Title: Long-term Safety Phase (Year 4)
Started [1] 0 89 [2] 91 0 0 0 0 40 49
Completed 0 81 86 0 0 0 0 38 44
Not Completed 0 8 5 0 0 0 0 2 5
Reason Not Completed
Adverse Event             0             2             0             0             0             0             0             0             0
Lack of Efficacy             0             1             0             0             0             0             0             0             1
Withdrawal by Subject             0             5             4             0             0             0             0             1             4
Lost to Follow-up             0             0             1             0             0             0             0             0             0
Miscellaneous             0             0             0             0             0             0             0             1             0
[1]
The PBO/APR 20 mg and 30 mg EE and XO patients from week 24-52 are combined within the LTSP
[2]
1 participant who completed Year 3 did not continue treatment in Year 4
Period Title: Long-term Safety Phase (Year 5)
Started [1] 0 81 86 0 0 0 0 38 44
Completed 0 71 80 0 0 0 0 37 41
Not Completed 0 10 6 0 0 0 0 1 3
Reason Not Completed
Adverse Event             0             1             1             0             0             0             0             0             1
Lack of Efficacy             0             2             1             0             0             0             0             0             0
Withdrawal by Subject             0             6             2             0             0             0             0             0             1
Lost to Follow-up             0             1             0             0             0             0             0             0             0
Miscellaneous             0             0             2             0             0             0             0             1             1
[1]
The PBO/APR 20 mg and 30 mg EE and XO patients from week 24-52 are combined within the LTSP
Arm/Group Title Placebo Apremilast 20mg Apremilast 30mg Total
Hide Arm/Group Description Participants initially randomized to receive placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape). Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase. Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase. Total of all reporting groups
Overall Number of Baseline Participants 176 175 176 527
Hide Baseline Analysis Population Description
Full Analysis Set was defined as participants who were randomized as specified in the protocol; one participant who was randomized in error and did not receive any dose of investigational product was excluded.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 176 participants 175 participants 176 participants 527 participants
50.5  (11.58) 49.2  (12.00) 48.4  (12.52) 49.4  (12.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 176 participants 175 participants 176 participants 527 participants
Female
86
  48.9%
95
  54.3%
96
  54.5%
277
  52.6%
Male
90
  51.1%
80
  45.7%
80
  45.5%
250
  47.4%
Duration of Psoriatic Arthritis   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 176 participants 175 participants 176 participants 527 participants
3.42  (5.103) 3.19  (4.706) 3.62  (5.041) 3.41  (4.947)
[1]
Measure Description: Psoriatic arthritis (PsA) is a chronic and progressive inflammatory arthritis that, depending on the method of ascertainment, occurs in 6% to 39% of patients with psoriasis. Disease onset typically occurs between the ages of 30 and 55 years and affects both sexes equally. In the majority of patients, psoriasis precedes PsA by several years. The diagnosis of PsA is made on clinical grounds in patients with psoriasis having skin, scalp or nail changes.
1.Primary Outcome
Title Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16
Hide Description A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set consisting of all participants randomized as specified in the protocol; one participant randomized in error and not receiving any dose of investigational product was excluded. Participants who withdrew early or did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20mg Apremilast 30mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Measure Type: Number
Unit of Measure: percentage of participants
15.9 28.0 30.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20mg
Comments In order to maintain the Type 1 error at the 0.05 significance level, the Hochberg procedure was to be used. The results of the endpoint were to be considered statistically significant if both the 30 mg apremilast dose versus placebo comparison and the 20 mg versus placebo comparison were statistically significant at the 0.05 significance level, or one of the comparisons was statistically significant at the 0.025 level.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0062
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 12.1
Confidence Interval (2-Sided) 95%
3.5 to 20.7
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30mg
Comments In order to maintain the Type 1 error at the 0.05 significance level, the Hochberg procedure was to be used. The results of the endpoint were to be considered statistically significant if both the 30 mg apremilast dose versus placebo comparison and the 20 mg versus placebo comparison were statistically significant at the 0.05 significance level, or one of the comparisons was statistically significant at the 0.025 level.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 14.8
Confidence Interval (2-Sided) 95%
6.1 to 23.5
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
2.Secondary Outcome
Title Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 16
Hide Description The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from baseline in the overall score indicate improvement in functional ability.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included; Last observation carried forward (LOCF) imputation was used.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.012  (0.0350) -0.156  (0.0349) -0.205  (0.0350)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments Pairwise comparisons (30 mg vs placebo and 20 mg vs placebo) were conducted conditional on the primary endpoint results. If the primary endpoint was statistically significant for both apremilast dose groups, pairwise comparisons for the HAQ-DI were to be evaluated at the 0.05 level using the Hochberg procedure. If only one apremilast dose was statistically significant, then only the comparison between that apremilast dose and placebo was conducted for the HAQ-DI score, at the 0.025 level.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group as a factor, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.168
Confidence Interval (2-Sided) 95%
-0.265 to -0.071
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30mg
Comments Pairwise comparisons (30 mg vs placebo and 20 mg vs placebo) were conducted conditional on the primary endpoint results. If the primary endpoint was statistically significant for both apremilast dose groups, pairwise comparisons for the HAQ-DI were to be evaluated at the 0.05 level using the Hochberg procedure. If only one apremilast dose was statistically significant, then only the comparison between that apremilast dose and placebo was conducted for the HAQ-DI score, at the 0.025 level.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group as a factor, and the baseline value as a covariate
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.217
Confidence Interval (2-Sided) 95%
-0.314 to -0.120
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With an ACR 20 Response at Week 24
Hide Description Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 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.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; Participants who discontinued early, escaped at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Measure Type: Number
Unit of Measure: percentage of participants
13.1 29.1 24.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 16.1
Confidence Interval (2-Sided) 95%
7.7 to 24.4
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0063
Comments Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 11.4
Confidence Interval (2-Sided) 95%
3.3 to 19.4
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
4.Secondary Outcome
Title Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 24
Hide Description The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive Apremilast 20 mg tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.012  (0.0370) -0.156  (0.0368) -0.207  (0.0369)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
Method ANCOVA
Comments Based on an analysis of covariance model for the change from baseline at Week 24, with treatment group as a factor and baseline value as a covariate
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.168
Confidence Interval (2-Sided) 95%
-0.271 to -0.065
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
Method ANCOVA
Comments Based on an analysis of covariance model for the change from baseline at Week 24, with treatment group as a factor and baseline value as a covariate
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.219
Confidence Interval (2-Sided) 95%
-0.322 to -0.117
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16
Hide Description The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) 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). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included; LOCF was used.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive Apremilast 20 mg tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.01  (0.588) 2.39  (0.586) 3.19  (0.590)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0043
Comments Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.
Method ANCOVA
Comments Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and baseline value as a covariate
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.38
Confidence Interval (2-Sided) 95%
0.75 to 4.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
Method ANCOVA
Comments Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and baseline value as a covariate
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.18
Confidence Interval (2-Sided) 95%
1.55 to 4.82
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16
Hide Description Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Measure Type: Number
Unit of Measure: percentage of participants
24.4 38.9 45.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0037
Comments Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 14.4
Confidence Interval (2-Sided) 95%
4.8 to 24.0
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 21.0
Confidence Interval (2-Sided) 95%
11.3 to 30.7
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
7.Secondary Outcome
Title Change From Baseline in Patient's Assessment of Pain at Week 16
Hide Description The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included; LOCF was used.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Least Squares Mean (Standard Error)
Unit of Measure: mm
-2.6  (1.81) -7.7  (1.79) -10.5  (1.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0485
Comments Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group as a factor, and the baseline value as a covariate
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.0
Confidence Interval (2-Sided) 95%
-10.0 to -0.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0022
Comments Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group as a factor, and the baseline value as a covariate
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -7.8
Confidence Interval (2-Sided) 95%
-12.8 to -2.8
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16
Hide Description The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline MASES > 0 (i.e., pre-existing enthesopathy) and at least 1 postbaseline value at or prior to Week 16 are included; LOCF was used.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 115 117 111
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.5  (0.24) -0.5  (0.24) -1.5  (0.25)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7696
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.8 to 0.6
Estimation Comments Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0038
Comments Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-1.7 to -0.3
Estimation Comments Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate
9.Secondary Outcome
Title Change From Baseline in Dactylitis Severity Score at Week 16
Hide Description Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants with a baseline dactylitis severity score > 0 (i.e., pre-existing dactylitis) and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 90 89 84
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.0  (0.25) -1.9  (0.25) -1.7  (0.26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-1.6 to -0.2
Estimation Comments Based on analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.4 to -0.0
Estimation Comments Based on analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate
10.Secondary Outcome
Title Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16
Hide Description The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 163 166 164
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.98  (0.770) -6.89  (0.763) -7.63  (0.768)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.91
Confidence Interval (2-Sided) 95%
-7.04 to -2.78
Estimation Comments Based on analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.65
Confidence Interval (2-Sided) 95%
-7.78 to -3.51
Estimation Comments Based on analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate
11.Secondary Outcome
Title Change From Baseline in the Disease Activity Score (DAS28) After 16 Weeks of Treatment
Hide Description The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 164 164 167
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.15  (0.076) -0.61  (0.076) -0.68  (0.075)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-0.67 to -0.25
Estimation Comments Based on analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.53
Confidence Interval (2-Sided) 95%
-0.74 to -0.32
Estimation Comments Based on analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate
12.Secondary Outcome
Title Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16
Hide Description The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 167 168 166
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.07  (0.631) 1.19  (0.629) 2.62  (.0633)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
-0.63 to 2.87
Estimation Comments Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 2.55
Confidence Interval (2-Sided) 95%
0.80 to 4.31
Estimation Comments Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor and the baseline value as a covariate
13.Secondary Outcome
Title Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24
Hide Description The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) 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). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.16  (0.609) 2.13  (0.605) 3.88  (0.611)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means Difference
Estimated Value 1.97
Confidence Interval (2-Sided) 95%
0.28 to 3.65
Estimation Comments Based on an analysis of covariance model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.72
Confidence Interval (2-Sided) 95%
2.02 to 5.41
Estimation Comments Based on an analysis of covariance model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate
14.Secondary Outcome
Title Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24
Hide Description Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; Participants who discontinued early, escaped early at Week 16, or who did not have sufficient data for a determination of response status at Week 24 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive Apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Measure Type: Number
Unit of Measure: percentage of participants
17.0 36.6 35.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 19.5
Confidence Interval (2-Sided) 95%
10.5 to 28.6
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 18.2
Confidence Interval (2-Sided) 95%
9.2 to 27.2
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution
15.Secondary Outcome
Title Change From Baseline in Participants Assessment of Pain at Week 24
Hide Description The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Least Squares Mean (Standard Error)
Unit of Measure: mm
-3.8  (1.83) -9.4  (1.82) -9.6  (1.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.6
Confidence Interval (2-Sided) 95%
-10.6 to -0.5
Estimation Comments Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.7
Confidence Interval (2-Sided) 95%
-10.8 to -0.7
Estimation Comments Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate
16.Secondary Outcome
Title Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24
Hide Description The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline MASES > 0 (i.e., pre-existing enthesopathy) and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase..
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 111 113 106
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.6  (0.25) -0.9  (0.25) -1.5  (0.26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-1.0 to 0.4
Estimation Comments Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-1.6 to -0.2
Estimation Comments Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.
17.Secondary Outcome
Title Change From Baseline in Dactylitis Severity Score at Week 24
Hide Description Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants with a baseline dactylitis severity score > 0 (i.e., pre-existing dactylitis) and at least 1 postbaseline value at or prior to Week 24 are included. LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive Apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 87 85 79
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.0  (0.26) -2.0  (0.26) -1.7  (0.27)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-1.7 to -0.3
Estimation Comments Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.4 to 0.1
Estimation Comments Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.
18.Secondary Outcome
Title Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
Hide Description The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.23  (0.807) -7.30  (0.803) -7.36  (0.810)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.07
Confidence Interval (2-Sided) 95%
-7.31 to -2.84
Estimation Comments Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.14
Confidence Interval (2-Sided) 95%
-7.38 to -2.89
Estimation Comments Based on an analysis of covariance model (Ancova) for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.
19.Secondary Outcome
Title Change From Baseline in Disease Activity Score (DAS 28) at Week 24
Hide Description The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.22  (0.084) -0.69  (0.084) -0.68  (0.084)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-0.70 to -0.23
Estimation Comments Based on an analysis of covariance (Ancova) model for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-0.69 to -0.22
Estimation Comments Based on an analysis of covariance model (Ancova) for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.
20.Secondary Outcome
Title Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24
Hide Description The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive Apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.25  (0.652) 1.37  (0.648) 2.58  (0.655)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
-0.68 to 2.93
Estimation Comments Based on an analysis of covariance model (Ancova) for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 2.33
Confidence Interval (2-Sided) 95%
0.52 to 4.15
Estimation Comments Based on an analysis of covariance model (Ancova) for the change from baseline at Week 24, with treatment group as a factor and the baseline value as a covariate.
21.Secondary Outcome
Title Percentage of Participants With ≥ 20% Improvement in Maastricht Ankylosing Spondylitis Entheses Score at Week 16
Hide Description Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline MASES > 0 (i.e., pre-existing enthesopathy) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive Apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 115 117 111
Measure Type: Number
Unit of Measure: percentage of participants
46.1 48.7 63.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.6
Confidence Interval (2-Sided) 95%
-10.2 to 15.5
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 17.0
Confidence Interval (2-Sided) 95%
4.2 to 29.8
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution
22.Secondary Outcome
Title Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16
Hide Description Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline dactylitis severity score > 0 (i.e., pre-existing dactylitis) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive Apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 90 89 84
Measure Type: Number
Unit of Measure: percentage of participants
60.0 66.3 61.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.3
Confidence Interval (2-Sided) 95%
-7.8 to 20.4
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
-12.6 to 16.4
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
23.Secondary Outcome
Title Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16
Hide Description The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Measure Type: Number
Unit of Measure: percentage of participants
25.0 41.1 44.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 16.1
Confidence Interval (2-Sided) 95%
6.4 to 25.8
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 19.3
Confidence Interval (2-Sided) 95%
9.6 to 29.1
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
24.Secondary Outcome
Title Percentage of Participants With MASES Improvement ≥ 20% at Week 24
Hide Description Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline MASES > 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 115 117 111
Measure Type: Number
Unit of Measure: percentage of participants
48.7 54.7 66.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.0
Confidence Interval (2-Sided) 95%
-6.8 to 18.8
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 18.0
Confidence Interval (2-Sided) 95%
5.3 to 30.6
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution
25.Secondary Outcome
Title Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24
Hide Description Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline dactylitis severity score > 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 90 89 84
Measure Type: Number
Unit of Measure: percentage of participants
57.8 69.7 63.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 11.9
Confidence Interval (2-Sided) 95%
-2.1 to 25.9
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 5.3
Confidence Interval (2-Sided) 95%
-9.2 to 19.8
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
26.Secondary Outcome
Title Percentage of Participants With Good or Moderate EULAR Response at Week 24
Hide Description The EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on th DAS-28. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2 A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Measure Type: Number
Unit of Measure: percentage of participants
17.0 34.9 28.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 17.8
Confidence Interval (2-Sided) 95%
8.8 to 26.8
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 11.4
Confidence Interval (2-Sided) 95%
2.7 to 20.0
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
27.Secondary Outcome
Title Percentage of Participants With a ACR 50 Response at Week 16
Hide Description Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive Apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Overall Number of Participants Analyzed 176 175 176
Measure Type: Number
Unit of Measure: Percentage of participants
4.5 11.4 11.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.9
Confidence Interval (2-Sided) 95%
1.3 to 12.5
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.8
Confidence Interval (2-Sided) 95%
1.2 to 12.4
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
28.Secondary Outcome
Title Percentage of Participants With a ACR 70 Response at Week 16
Hide Description Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 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.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Measure Type: Number
Unit of Measure: percentage of participants
1.1 4.0 4.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
-0.4 to 6.2
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-0.4 to 6.1
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution
29.Secondary Outcome
Title Percentage of Participants With a ACR 50 Response at Week 24
Hide Description Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 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.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Measure Type: Number
Unit of Measure: percentage of participants
6.3 16.0 12.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 9.8
Confidence Interval (2-Sided) 95%
3.2 to 16.3
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.3
Confidence Interval (2-Sided) 95%
0.2 to 12.3
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution
30.Secondary Outcome
Title Percentage of Participants With a ACR 70 Response at Week 24
Hide Description Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 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.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 176 175 176
Measure Type: Number
Unit of Measure: percentage of participants
4.0 4.0 4.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-4.1 to 4.1
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-3.7 to 4.8
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
31.Secondary Outcome
Title Percentage of Participants With Pre-existing Enthesopathy Whose Maastricht Ankylosing Spondylitis Entheses Score Improves to 0 at Week 16
Hide Description Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline MASES > 0 (i.e., pre-existing enthesopathy) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 115 117 111
Measure Type: Number
Unit of Measure: percentage of participants
19.1 21.4 36.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
-8.1 to 12.6
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 17.8
Confidence Interval (2-Sided) 95%
6.3 to 29.3
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
32.Secondary Outcome
Title Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves to 0 at Week 16
Hide Description Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline dactylitis severity score > 0 (i.e., pre-existing dactylitis) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 90 89 84
Measure Type: Number
Unit of Measure: percentage of participants
33.3 42.7 40.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 9.4
Confidence Interval (2-Sided) 95%
-4.8 to 23.5
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 7.1
Confidence Interval (2-Sided) 95%
-7.2 to 21.5
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
33.Secondary Outcome
Title Percentage of Participants Achieving a MASES Score of Zero at Week 24
Hide Description Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline MASES > 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 115 117 111
Measure Type: Number
Unit of Measure: percentage of participants
22.6 29.1 37.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.5
Confidence Interval (2-Sided) 95%
-4.8 to 17.7
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 15.2
Confidence Interval (2-Sided) 95%
3.4 to 27.1
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
34.Secondary Outcome
Title Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24
Hide Description Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants with a baseline dactylitis severity score > 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily (BID) in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).
Participants initially randomized to receive apremilast 20 mg tablets twice daily in the 24-week placebo-controlled phase.
Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed 90 89 84
Measure Type: Number
Unit of Measure: percentage of participants
35.6 46.1 40.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 10.5
Confidence Interval (2-Sided) 95%
-3.8 to 24.8
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 4.9
Confidence Interval (2-Sided) 95%
-9.5 to 19.3
Estimation Comments Two-sided 95% CI of the proportion difference is based on the normal approximation to the binomial distribution.
35.Secondary Outcome
Title Percentage of Participants With a ACR 20 Response at Week 52
Hide Description Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in 78 tender joint count; ≥ 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. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The Apremilast Subjects as Randomized/Re-randomized (AAR) Population consists of all participants who were randomized or re-randomized to apremilast at any time during the study. Only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.
Arm/Group Title Placebo / Apremilast 20 mg Placebo / Apremilast 30 mg Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.
Participants initially randomized to receive 20 mg apremilast tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Overall Number of Participants Analyzed 62 67 131 138
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
59.7
(46.4 to 71.9)
56.7
(44.0 to 68.8)
53.4
(44.5 to 62.2)
58.7
(50.0 to 67.0)
36.Secondary Outcome
Title Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52
Hide Description The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.
Arm/Group Title Placebo / Apremilast 20 mg Placebo / Apremilast 30 mg Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.
Participants initially randomized to receive 20 mg apremilast tablets twice daily
Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Overall Number of Participants Analyzed 62 68 132 139
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.21  (0.450) -0.25  (0.533) -0.32  (0.559) -0.39  (0.567)
37.Secondary Outcome
Title Change From Baseline in the SF-36v2 Physical Functioning Scale Score at Week 52
Hide Description The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) 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). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.
Arm/Group Title Placebo / Apremilast 20 mg Placebo / Apremilast 30 mg Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.
Participants initially randomized to receive 20 mg apremilast tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Overall Number of Participants Analyzed 62 68 132 139
Mean (Standard Deviation)
Unit of Measure: units on a scale
7.76  (8.236) 6.87  (7.241) 5.68  (8.467) 5.87  (8.008)
38.Secondary Outcome
Title Percentage of Participants With a Modified PsARC Response at Week 52
Hide Description Measure Description: Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. Two-sided 95% confidence interval is based on the Clopper-Pearson method.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.
Arm/Group Title Placebo / Apremilast 20 mg Placebo / Apremilast 30 mg Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.
Participants initially randomized to receive 20 mg apremilast tablets twice daily
Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Overall Number of Participants Analyzed 61 67 131 139
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
73.8
(60.9 to 84.2)
79.1
(67.4 to 88.1)
75.6
(67.3 to 82.7)
75.9
(67.9 to 82.8)
39.Secondary Outcome
Title Change From Baseline in the Participants Assessment of Pain Using the Visual Analog Scale at Week 52
Hide Description The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.
Arm/Group Title Placebo/Apremilast 20 mg Placebo / Apremilast 30 mg Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.
Participants initially randomized to receive 20 mg apremilast tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Overall Number of Participants Analyzed 62 68 132 139
Mean (Standard Deviation)
Unit of Measure: mm
-13.1  (25.57) -18.9  (24.28) -15.6  (27.29) -14.2  (28.14)
40.Secondary Outcome
Title Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52
Hide Description The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a baseline value > 0 (i.e., pre-existing enthesopathy) and a Week 52 value are included.
Arm/Group Title Placebo / Apremilast 20 mg Placebo/Apremilast 30 mg Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.
Participants initially randomized to receive 20 mg apremilast tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily.
Overall Number of Participants Analyzed 41 42 91 176
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.7  (2.38) -1.8  (2.34) -1.5  (2.62) -1.8  (3.03)
41.Secondary Outcome
Title Change From Baseline in the Dactylitis Severity Score at Week 52
Hide Description Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present
Time Frame Baseline and Week 52
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Hide Analysis Population Description
The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a baseline value > 0 (i.e., pre-existing dactylitis) and a Week 52 value are included.
Arm/Group Title Placebo / Apremilast 20 mg Placebo / Apremilast 30 mg Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.
Participants initially randomized to receive 20 mg apremilast tablets twice daily.
Participants initially randomized to receive 30 mg apremilast tablets twice daily
Overall Number of Participants Analyzed 32 38 70 64
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.2  (1.89) -2.9  (2.47) -2.2  (4.09) -2.9  (3.55)
42.Secondary Outcome
Title Change From Baseline in the CDAI Score at Week 52
Hide Description The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: 28 tender joint count (TJC), 28 swollen joint count (SJC), Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.
Arm/Group Title Placebo / Apremilast 20 mg Placebo / Apremilast 30 mg Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily
Participants who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twic