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PALACE 2: Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis (PALACE2)

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: NCT01212757
Recruitment Status : Completed
First Posted : October 1, 2010
Results First Posted : May 19, 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 + 20 mg Apremilast
Drug: Placebo + 30 mg Apremilast
Enrollment 488
Recruitment Details This study was a multicenter study with 84 sites from the United States, Canada, Europe, Russia, Australia, South Africa and Taiwan.
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) Placebo/Apremilast 30 mg (Long-Term Safety Phase)
Hide Arm/Group Description Participants initially randomized to 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose). Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase. Participants initially randomized to placebo twice daily in the 24-week placebo-controlled phase were re-randomized due to early escape (EE) at Week 16 and began receiving 20 mg apremilast tablets twice a day in the active treatment phase. Participants initially randomized to receive placebo twice daily in the 24-week placebo-controlled phase were re-randomized at Week 24 (XO) to 20 mg apremilast tablets twice daily in the active treatment phase. Participants initially randomized to placebo twice daily in the 24-week placebo controlled phase were re-randomized due to early escape (EE) at Week 16 to 30 mg apremilast tablets twice daily in the active-treatment phase. Participants initially randomized to placebo twice daily in the 24-week placebo-controlled phase were re-randomized at Week 24 to 30 mg apremilast tablets twice daily in the active treatment phase. Participants initially randomized to placebo tablets twice daily during the placebo controlled phase were re-randomized to 20 mg apremilast twice daily at Week 16 or Week 24 and continued receiving apremilast 20 mg twice daily in the active treatment / long-term safety phase. (After 30 mg apremilast twice daily was identified as the optimal dose, all participants receiving 20 mg apremilast twice daily were switched to the 30 mg apremilast twice daily dose). Participants initially randomized to placebo tablets twice daily during the 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 twice daily in the active treatment / long-term safety phase.
Period Title: Placebo-controlled Phase (Week 0 - 24)
Started 162 163 163 0 0 0 0 0 0
Received Treatment 159 163 162 0 0 0 0 0 0
Completed Week 16 148 151 149 0 0 0 0 0 0
Early Escape at Week 16 88 [1] 59 [2] 64 0 0 0 0 0 0
Completed 143 [3] 143 142 0 0 0 0 0 0
Not Completed 19 20 21 0 0 0 0 0 0
Reason Not Completed
Adverse Event             4             5             12             0             0             0             0             0             0
Lack of Efficacy             3             2             2             0             0             0             0             0             0
Withdrawal by Subject             7             9             3             0             0             0             0             0             0
Randomization Error             3             0             1             0             0             0             0             0             0
Lost to Follow-up             1             1             2             0             0             0             0             0             0
Protocol Violation             0             1             1             0             0             0             0             0             0
Other             1             2             0             0             0             0             0             0             0
[1]
Two participants who escaped early did not complete Week 24
[2]
Three participants who escaped early did not complete Week 24
[3]
Two participants who completed Week 24 did not enter the active treatment phase
Period Title: Active Treatment Phase (Weeks 24 - 52)
Started 0 137 [1] 134 [2] 43 27 41 [3] 28 0 0
Completed 0 125 114 35 25 34 28 0 0
Not Completed 0 12 20 8 2 7 0 0 0
Reason Not Completed
Adverse Event             0             2             3             1             0             2             0             0             0
Lack of Efficacy             0             5             7             4             0             2             0             0             0
Non-compliance with Study Drug             0             0             2             0             0             0             0             0             0
Withdrawal by Subject             0             3             7             3             1             3             0             0             0
Lost to Follow-up             0             1             0             0             1             0             0             0             0
Other             0             1             1             0             0             0             0             0             0
[1]
6 participants who completed Week 24 did not enter the Week 24-52 active treatment phase
[2]
8 participants who completed Week 24 did not enter the Week 24-52 active treatment phase
[3]
2 participants who EE and completed Week 24 did not enter the Week 24-52 active treatment phase
Period Title: Long-Term Safety Phase (Year 2)
Started 0 119 [1] 109 [2] 0 0 0 0 58 [3] 60 [4]
Completed 0 107 95 0 0 0 0 48 51
Not Completed 0 12 14 0 0 0 0 10 9
Reason Not Completed
Miscellaneous             0             0             0             0             0             0             0             0             1
Adverse Event             0             1             1             0             0             0             0             2             2
Lack of Efficacy             0             4             2             0             0             0             0             4             0
Withdrawal by Subject             0             7             9             0             0             0             0             4             6
Lost to Follow-up             0             0             2             0             0             0             0             0             0
[1]
6 participants who completed Week 52 did not enter the long-term safety phase
[2]
5 participants who completed Week 52 did not enter the long-term safety phase
[3]
Combined PBO-APR 20EE+XO;2 participants who completed Week 52 did not enter long-term safety phase
[4]
Combined PBO-APR 30EE+XO;2 participants who completed Week 52 did not enter long-term safety phase
Period Title: Long-Term Safety Phase (Year 3)
Started 0 107 95 0 0 0 0 48 51
Completed 0 89 84 0 0 0 0 42 46
Not Completed 0 18 11 0 0 0 0 6 5
Reason Not Completed
Adverse Event             0             4             1             0             0             0             0             2             0
Lack of Efficacy             0             8             5             0             0             0             0             3             1
Non-compliance with study drug             0             0             1             0             0             0             0             0             0
Withdrawal by Subject             0             5             1             0             0             0             0             1             1
Lost to Follow-up             0             0             0             0             0             0             0             0             1
Protocol Violation             0             1             0             0             0             0             0             0             0
Miscellaneous             0             0             3             0             0             0             0             0             2
Period Title: Long-Term Safety Phase (Year 4)
Started 0 89 84 0 0 0 0 41 [1] 46
Completed 0 80 77 0 0 0 0 37 39
Not Completed 0 9 7 0 0 0 0 4 7
Reason Not Completed
Miscellaneous             0             2             0             0             0             0             0             0             1
Adverse Event             0             1             2             0             0             0             0             1             1
Lack of Efficacy             0             2             2             0             0             0             0             1             1
Withdrawal by Subject             0             4             2             0             0             0             0             1             3
Death             0             0             1             0             0             0             0             0             1
Lost to Follow-up             0             0             0             0             0             0             0             1             0
[1]
1 participant who completed Year 3 did not continue treatment in Year 4
Period Title: Long-Term Safety Phase (Year 5)
Started 0 80 77 0 0 0 0 38 [1] 39
Completed 0 72 69 0 0 0 0 33 37
Not Completed 0 8 8 0 0 0 0 5 2
Reason Not Completed
Withdrawal by Subject             0             3             3             0             0             0             0             1             1
Adverse Event             0             2             2             0             0             0             0             2             0
Lack of Efficacy             0             1             2             0             0             0             0             2             1
Non-compliance with study drug             0             1             0             0             0             0             0             0             0
Miscellaneous             0             1             1             0             0             0             0             0             0
[1]
1 participant was only counted in year 5 but not in 4 year due to late APR dispensing
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg Total
Hide Arm/Group Description Participants initially randomized to 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose). Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase. Total of all reporting groups
Overall Number of Baseline Participants 159 163 162 484
Hide Baseline Analysis Population Description
Full analysis set consisting of all participants who were randomized as specified in the protocol. Four participants who were randomized in error and did not receive any dose of investigational product are excluded.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 159 participants 163 participants 162 participants 484 participants
51.2  (10.97) 50.9  (11.82) 50.5  (11.20) 50.9  (11.32)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 159 participants 163 participants 162 participants 484 participants
Female
85
  53.5%
95
  58.3%
95
  58.6%
275
  56.8%
Male
74
  46.5%
68
  41.7%
67
  41.4%
209
  43.2%
Duration of Psoriatic Arthritis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 159 participants 163 participants 162 participants 484 participants
7.76  (8.254) 7.83  (8.621) 6.82  (7.592) 7.47  (8.163)
1.Primary Outcome
Title Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16
Hide Description Percentage of participants with an 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 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set consisting of all participants randomized as specified in the protocol; participants who were randomized in error and did not receive any dose of study drug were excluded. Participants who withdrew 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 159 163 162
Measure Type: Number
Unit of Measure: percentage of participants
18.9 37.4 32.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
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 0.0060
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments 2-sided p-value is based on the Cochran-Mantel-Haenszel (CMH) test adjusting for baseline disease modifying antirheumatic drug (DMARD) use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 13.4
Confidence Interval (2-Sided) 95%
4.0 to 22.7
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% confidence interval (CI) is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
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 0.0002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 18.7
Confidence Interval (2-Sided) 95%
9.1 to 28.2
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
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 mean 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 30 mg
Hide Arm/Group Description:
Participants initially randomized to 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 153 159 154
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.053  (0.0358) -0.157  (0.0351) -0.193  (0.0354)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 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 0.0042
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.140
Confidence Interval (2-Sided) 95%
-0.236 to -0.045
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
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 0.0320
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.104
Confidence Interval (2-Sided) 95%
-0.199 to -0.009
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 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 159 163 162
Measure Type: Number
Unit of Measure: percentage of participants
15.7 31.3 24.7
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]
Statistical Test of Hypothesis P-Value 0.0394
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 Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 9.2
Confidence Interval (2-Sided) 95%
0.5 to 17.8
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the Cochran-Mantel-Haenszel (CMH) weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
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 0.0009
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 Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 15.7
Confidence Interval (2-Sided) 95%
6.7 to 24.7
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the Cochran-Mantel-Haenszel (CMH) weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
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 mean 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 153 159 154
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.085  (0.0377) -0.165  (0.0370) -0.206  (0.0372)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
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.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0191
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.121
Confidence Interval (2-Sided) 95%
-0.222 to -0.020
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1179
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.080
Confidence Interval (2-Sided) 95%
-0.180 to 0.020
Estimation Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
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). 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 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 153 159 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.81  (0.678) 2.17  (0.664) 2.91  (0.671)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
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
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0237
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.10
Confidence Interval (2-Sided) 95%
0.28 to 3.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
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
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1388
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.36
Confidence Interval (2-Sided) 95%
-0.44 to 3.15
Estimation Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
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 mm = lowest disease activity and 100 mm = highest; - Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 159 163 162
Measure Type: Number
Unit of Measure: percentage of participants
33.3 47.9 48.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
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.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0065
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 14.9
Confidence Interval (2-Sided) 95%
4.3 to 25.5
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the Cochran-Mantel-Haenszel (CMH) weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0071
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 14.7
Confidence Interval (2-Sided) 95%
4.1 to 25.2
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the Cochran-Mantel-Haenszel (CMH) weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 151 157 152
Least Squares Mean (Standard Error)
Unit of Measure: mm
-7.0  (1.93) -12.5  (1.89) -11.9  (1.90)
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]
Statistical Test of Hypothesis P-Value 0.0648
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.9
Confidence Interval (2-Sided) 95%
-10.0 to 0.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
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 0.0347
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.5
Confidence Interval (2-Sided) 95%
-10.6 to -0.4
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 Archilles 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 100 105 97
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.0  (0.29) -0.9  (0.28) -1.4  (0.29)
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]
Statistical Test of Hypothesis P-Value 0.3496
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.2 to 0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8874
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.7 to 0.8
Estimation Comments [Not Specified]
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 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) 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 63 75 70
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.1  (0.28) -0.8  (0.26) -1.3  (0.26)
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]
Statistical Test of Hypothesis P-Value 0.5438
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.0 to 0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
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 0.3759
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.0
Estimation Comments [Not Specified]
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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 149 155 146
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.30  (0.871) -7.75  (0.851) -6.81  (0.869)
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]
Statistical Test of Hypothesis P-Value 0.0035
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.51
Confidence Interval (2-Sided) 95%
-5.86 to -1.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
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 [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.45
Confidence Interval (2-Sided) 95%
-6.76 to -2.14
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in the Disease Activity Score (DAS28) at Week 16
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 distal interphalangeal (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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 150 156 151
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.27  (0.082) -0.74  (0.080) -0.67  (0.080)
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]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.61 to -0.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
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 Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-0.68 to -0.25
Estimation Comments [Not Specified]
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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 153 157 154
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.63  (0.724) 0.91  (0.712) 2.75  (0.715)
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]
Statistical Test of Hypothesis P-Value 0.0318
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.12
Confidence Interval (2-Sided) 95%
0.19 to 4.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
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 0.7803
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.27
Confidence Interval (2-Sided) 95%
-1.65 to 2.20
Estimation Comments [Not Specified]
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). 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 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 153 159 154
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
1.44  (0.688) 2.97  (0.673) 3.30  (0.679)
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]
Statistical Test of Hypothesis P-Value 0.0473
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.86
Confidence Interval (2-Sided) 95%
0.02 to 3.70
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
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 0.0997
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.53
Confidence Interval (2-Sided) 95%
-0.29 to 3.35
Estimation Comments [Not Specified]
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 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = 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 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 159 163 162
Measure Type: Number
Unit of Measure: percentage of participants
24.5 39.9 32.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1195
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 7.8
Confidence Interval (2-Sided) 95%
-1.9 to 17.5
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0026
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 15.5
Confidence Interval (2-Sided) 95%
5.6 to 25.5
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
15.Secondary Outcome
Title Change From Baseline in Patient's 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 152 158 153
Least Squares Mean (Standard Error)
Unit of Measure: mm
-8.0  (1.90) -11.5  (1.86) -9.7  (1.88)
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]
Statistical Test of Hypothesis P-Value 0.5067
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-6.8 to 3.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
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 0.1762
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS mean Difference
Estimated Value -3.5
Confidence Interval (2-Sided) 95%
-8.5 to 1.6
Estimation Comments [Not Specified]
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 Archilles 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 100 105 98
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.9  (0.29) -0.9  (0.28) -1.3  (0.29)
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]
Statistical Test of Hypothesis P-Value 0.2719
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.2 to 0.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9727
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-0.8 to 0.7
Estimation Comments [Not Specified]
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 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 63 75 71
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.1  (0.27) -0.9  (0.25) -1.4  (0.26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3705
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-1.0 to 0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6777
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.6 to 0.8
Estimation Comments [Not Specified]
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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 149 155 148
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.21  (0.884) -7.71  (0.864) -6.35  (0.878)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0097
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.14
Confidence Interval (2-Sided) 95%
-5.52 to -0.76
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.50
Confidence Interval (2-Sided) 95%
-6.85 to -2.16
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline in the Disease Activity Score (DAS28) 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 150 157 152
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.27  (0.084) -0.73  (0.082) -0.65  (0.083)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.60 to -0.15
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-0.68 to -0.23
Estimation Comments [Not Specified]
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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 153 157 154
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.52  (0.721) 0.68  (0.710) 2.65  (0.713)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0303
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.14
Confidence Interval (2-Sided) 95%
0.20 to 4.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8704
Comments [Not Specified]
Method ANCOVA
Comments Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS mean Difference
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-1.76 to 2.08
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Percentage of Participants With MASES Improvement ≥ 20% 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 Archilles 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 104 107 101
Measure Type: Number
Unit of Measure: percentage of participants
52.9 54.2 56.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6022
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 3.6
Confidence Interval (2-Sided) 95%
-9.9 to 17.2
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8462
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-12.1 to 14.7
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights.
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 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 66 77 73
Measure Type: Number
Unit of Measure: percentage of participants
59.1 62.3 61.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7337
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-13.3 to 18.9
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the Cochran-Mantel-Haenszel (CMH) weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6881
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 3.3
Confidence Interval (2-Sided) 95%
-12.7 to 19.3
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the Cochran-Mantel-Haenszel (CMH) weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
23.Secondary Outcome
Title Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16
Hide Description A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. 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 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 159 163 162
Measure Type: Number
Unit of Measure: percentage of participants
31.4 53.4 48.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 17.5
Confidence Interval (2-Sided) 95%
7.0 to 27.9
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 22.1
Confidence Interval (2-Sided) 95%
11.7 to 32.5
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
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 Archilles 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 104 107 101
Measure Type: Number
Unit of Measure: percentage of participants
51.0 57.0 57.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3376
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 6.6
Confidence Interval (2-Sided) 95%
-6.8 to 20.0
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3756
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 6.1
Confidence Interval (2-Sided) 95%
-7.2 to 19.4
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
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 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 66 77 73
Measure Type: Number
Unit of Measure: percentage of participants
62.1 68.8 68.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3959
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 6.8
Confidence Interval (2-Sided) 95%
-8.7 to 22.2
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3941
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 6.8
Confidence Interval (2-Sided) 95%
-8.7 to 22.4
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the Cochran-Mantel-Haenszel (CMH) weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
26.Secondary Outcome
Title Percentage of Participants With Good or Moderate EULAR Response at Week 24
Hide Description EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 159 163 162
Measure Type: Number
Unit of Measure: percentage of participants
21.4 41.7 33.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0142
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 12.1
Confidence Interval (2-Sided) 95%
2.6 to 21.7
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 20.5
Confidence Interval (2-Sided) 95%
10.8 to 30.3
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
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: o Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 159 163 162
Measure Type: Number
Unit of Measure: percentage of participants
5.0 14.7 10.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0589
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 5.6
Confidence Interval (2-Sided) 95%
-0.2 to 11.3
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 9.8
Confidence Interval (2-Sided) 95%
3.4 to 16.1
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
28.Secondary Outcome
Title Percentage of Participants With an 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: o Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 159 163 162
Measure Type: Number
Unit of Measure: percentage of participants
0.6 3.7 1.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5620
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-1.5 to 2.7
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0570
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 3.1
Confidence Interval (2-Sided) 95%
-0.0 to 6.2
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
29.Secondary Outcome
Title Percentage of Participants With an 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: o Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 159 163 162
Measure Type: Number
Unit of Measure: percentage of participants
8.8 14.1 11.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3629
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 3.1
Confidence Interval (2-Sided) 95%
-3.5 to 9.6
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1323
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 5.4
Confidence Interval (2-Sided) 95%
-1.5 to 12.3
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
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 30 mg
Hide Arm/Group Description:
Participants initially randomized to 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 159 163 162
Measure Type: Number
Unit of Measure: percentage of participants
3.1 5.5 2.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7273
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-4.3 to 3.0
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2929
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 2.4
Confidence Interval (2-Sided) 95%
-2.0 to 6.8
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
31.Secondary Outcome
Title Percentage of Participants Achieving a MASES Score of Zero 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 Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time Frame 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 104 107 101
Measure Type: Number
Unit of Measure: percentage of participants
23.1 29.0 20.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7023
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-13.5 to 9.1
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3305
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 5.9
Confidence Interval (2-Sided) 95%
-5.9 to 17.7
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
32.Secondary Outcome
Title Percentage of Participants Achieving a Dactylitis Score of Zero 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 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 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 66 77 73
Measure Type: Number
Unit of Measure: percentage of participants
40.9 42.9 41.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9698
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-16.0 to 16.6
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8205
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
-14.3 to 18.1
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
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 Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.
Time Frame 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 104 107 101
Measure Type: Number
Unit of Measure: percentage of participants
24.0 29.9 22.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8424
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-12.7 to 10.3
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3395
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 5.9
Confidence Interval (2-Sided) 95%
-6.0 to 17.8
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
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 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 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 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 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued receiving 20 mg apremilast tablets twice daily in the 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 30 mg apremilast BID dose).
Participants initially randomized to 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase, continued receiving 30 mg apremilast tablets twice daily in the active treatment / long-term safety phase.
Overall Number of Participants Analyzed 68 59 68
Measure Type: Number
Unit of Measure: percentage of participants
40.9 44.2 46.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4811
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 5.9
Confidence Interval (2-Sided) 95%
-10.3 to 22.1
Estimation Comments Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.