Certolizumab Pegol in Subjects With Adult Onset Active and Progressive Psoriatic Arthritis

• ClinicalTrials.gov Identifier: NCT01087788
• Recruitment Status: Completed
• First Posted: March 16, 2010
• Results First Posted: February 25, 2014
• Last Update Posted: August 1, 2018
• Sponsor: UCB BIOSCIENCES GmbH
• Information provided by (Responsible Party): UCB Pharma ( UCB BIOSCIENCES GmbH )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Arthritis, Psoriatic
• Interventions: Biological: CZP 200 mg Q2W; Biological: CZP 400 mg Q4W; Other: Placebo
• Enrollment: 409

Participant Flow

Recruitment Details	This study started to enroll patients in March 2010 and concluded in August 2015.
Pre-assignment Details	The study included a 24-week Double-Blind, a 24-week Dose-Blind, and an Open-Label Treatment Period. 409 subjects are included in Randomized Set (RS) shown in the Participant Flow, which is an Intention- to- Treat (ITT) dataset.

Arm/Group Title	Placebo	CZP 200 mg Q2W	CZP 400 mg Q4W
Arm/Group Description	Matching Placebo (PBO) to Certolizumab Pegol (CZP) injections from Week 0 to Week 24. Placebo subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group and were re-randomized to either CZP 200 mg Q2W or CZP 400 mg Q4W arm on Week 16. After 24 weeks, all subjects were re-randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W).	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards. Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind.
Period Title: 24-weeks Double-blind Period
Started	136	138	135
Received CZP 200 mg Q2W at 16 Weeks	30 [1]	0 [2]	0 [2]
Received CZP 400 mg Q4W at 16 Weeks	29 [3]	0 [2]	0 [2]
Completed	120	128	120
Not Completed	16	10	15
Reason Not Completed
Lack of Efficacy	2	0	1
Protocol Violation	0	1	0
Lost to Follow-up	4	1	1
Withdrawal by Subject	7	2	5
AE, serious fatal	0	1	1
AE, serious non-fatal	0	2	3
AE, non-serious non-fatal	2	1	2
AE, unknown type	0	0	1
Patient (P) does not want to attend	1	0	0
Protocol violation (decision of monitor)	0	1	0
Exclusion criteria were not met	0	1	0
P cannot comply with scheduled visits	0	0	1
[1] 30 subjects left the Placebo group and were re-randomized to CZP 200 mg Q2W on Week 16.; [2] not applicable for this arm; [3] 29 subjects left the Placebo group and were re-randomized to CZP 400 mg Q4W on Week 16.
Period Title: 24-weeks Dose-blind Period
Started	120	128	120
Received CZP 200 mg Q2W at 24 Weeks	60 [1]	0 [2]	0 [2]
Received CZP 400 mg Q2W at 24 Weeks	60 [3]	0 [2]	0 [2]
Completed	113	123	114
Not Completed	7	5	6
Reason Not Completed
Lack of Efficacy	0	2	1
Lost to Follow-up	1	0	1
Withdrawal by Subject	1	0	0
AE, serious fatal	0	1	0
AE, serious non-fatal	2	1	2
AE, non-serious non-fatal	2	1	1
Sponsor decision following missed visits	1	0	0
Patient moved	0	0	1
[1] Sum of subjects re-randomized to CZP 200mg Q2W at week 16 (30 subjects) and at week 24 (30 subjects); [2] not applicable for this arm; [3] Sum of subjects re-randomized to CZP 400mg Q2W at week 16 (29 subjects) and at week 24 (31 subjects)
Period Title: Open-Label Period (OL-P)
Started	111 [1]	121 [1]	114
Completed	81	97	86
Not Completed	30	24	28
Reason Not Completed
Lack of Efficacy	4	2	3
Protocol Violation	2	1	0
Lost to Follow-up	0	4	2
Withdrawal by Subject	13	8	10
AE, serious fatal	2	0	1
AE, serious non-fatal	1	3	4
AE, non-serious non-fatal	6	4	4
SAE, non-fatal+AE, non-serious non-fatal	0	1	0
AE, non-serious unknown	1	0	0
Sponsor request	1	0	0
Principal investigator decision	0	1	2
No participation in study extension	0	0	1
Personal reasons	0	0	1
[1] 2 subj. completed the Dose-Blind Period, then withdrew from the study rather than entering the OL-P.

Baseline Characteristics

Arm/Group Title		Placebo	CZP 200 mg Q2W	CZP 400 mg Q4W	Total Title
Arm/Group Description		Matching Placebo to Certolizumab Pegol (CZP) injections from Week 0 to Week 24. Placebo subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group and were re-randomized to either CZP 200 mg Q2W or CZP 400 mg Q4W arm on Week 16. After 24 weeks, all subjects were re-randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W).	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards. Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind.	[Not Specified]
Overall Number of Baseline Participants		136	138	135	409
Baseline Analysis Population Description		409 subjects are included in Randomized Set (RS) shown in Baseline Characteristics, which is an Intention-to-Treat (ITT) dataset.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	138 participants	135 participants	409 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	129 94.9%	126 91.3%	128 94.8%	383 93.6%
	>=65 years	7 5.1%	12 8.7%	7 5.2%	26 6.4%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	136 participants	138 participants	135 participants	409 participants
		47.3 (11.1)	48.2 (12.3)	47.1 (10.8)	47.6 (11.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	138 participants	135 participants	409 participants
	Female	79 58.1%	74 53.6%	73 54.1%	226 55.3%
	Male	57 41.9%	64 46.4%	62 45.9%	183 44.7%

Outcome Measures

1. Primary Outcome

Title	American College of Rheumatology 20 (ACR20) Response at Week 12
Description	ACR20 responders are those subjects with at least 20 % improvement from Baseline (BL) for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intention-to-treat dataset was the Randomized Set (RS). RS with non-responder imputation: subjects who withdrew for any reason or placebo subjects who used escape medication are considered as nonresponders from drop out timepoint or when escape therapy was initiated. Subjects with missing data at a visit are non-responders for that visit, too.

Arm/Group Title	Placebo (Randomized Set)	CZP 200 mg Q2W (Randomized Set)	CZP 400 mg Q4W (Randomized Set)
Arm/Group Description:	Matching Placebo to Certolizumab Pegol (CZP) injections from Week 0 to Week 24. Placebo subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group and were re-randomized to either CZP 200 mg Q2W or CZP 400 mg Q4W arm on Week 16. After 24 weeks, all subjects were re-randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W).	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards. Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind.
Overall Number of Participants Analyzed	136	138	135
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	24.3; (17.1 to 31.5)	58.0; (49.7 to 66.2)	51.9; (43.4 to 60.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Randomized Set), CZP 200 mg Q2W (Randomized Set)
	Comments	A hierarchical test procedure was applied to protect the overall significance level for the multiplicity of dose groups and endpoints. Conditional on the first test being significant, the second hypothesis was tested with the same alpha level of 5 %. Statistical testing for the following hypotheses was performed only if the previous null hypothesis in the hierarchy was rejected.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Difference of Certolizumab Pegol 200 mg versus Placebo (and corresponding 95 % Confidence Interval and p-value) were estimated using a standard two-sided Wald asymptotic test with a 5 % alpha level.
	Method	Wald-test, 2-sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	33.7
	Confidence Interval	(2-Sided) 95%; 22.8 to 44.6
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (Randomized Set), CZP 400 mg Q4W (Randomized Set)
	Comments	A hierarchical test procedure was applied to protect the overall significance level for the multiplicity of dose groups and endpoints. Conditional on the first test being significant, the second hypothesis was tested with the same alpha level of 5 %. Statistical testing for the following hypotheses was performed only if the previous null hypothesis in the hierarchy was rejected.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Difference of Certolizumab Pegol 400 mg versus Placebo (and corresponding 95 % Confidence Interval and p-value) were estimated using a standard two-sided Wald asymptotic test with a 5 % alpha level.
	Method	Wald-test, 2-sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	27.6
	Confidence Interval	(2-Sided) 95%; 16.5 to 38.7
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Change From Baseline in Modified Total Sharp Score (mTSS) in Modification for Psoriatic Arthritis at Week 24
Description	Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 64 and 52 joints, respectively, with higher scores representing greater damage. mTSS (bone erosions) ranges from 0 (best possible outcome) to 320 (worst possible outcome); mTSS (joint space narrowing) ranges from 0 (best possible outcome) to 208 (worst possible outcome); and total score ranges from 0 (best possible outcome) to 528 (worst possible outcome). For the pre-defined analysis of this outcome measure, 0 was used for Baseline and the maximum observed mTSS value was used for Week 24 for those subjects which had less than 2 radiographs. The re-analysis is restricted to those subjects in the Randomized Set who have at least 2 x-ray values at scheduled visits, which are at least 8 weeks apart.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Intention-to-treat dataset was the Randomized Set (RS). RS with imputation: for subjects who withdrew for any reason, or subjects with missing Week 24 measurements, or placebo subjects who used escape medication, scores are linearly extrapolated from the last two radiographs prior to early withdrawal or Week 24 or before receiving CZP.

Arm/Group Title	Placebo (Randomized Set)	CZP 200 mg Q2W (Randomized Set)	CZP 400 mg Q4W (Randomized Set)	CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set)
Arm/Group Description:	Matching Placebo to Certolizumab Pegol (CZP) injections from Week 0 to Week 24. Placebo subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group and were re-randomized to either CZP 200 mg Q2W or CZP 400 mg Q4W arm on Week 16. After 24 weeks, all subjects were re-randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W).	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards. Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind.	This combined group includes subjects of the two treatment arms CZP 200 mg Q2W and CZP 400 mg Q4W used in some analyses. Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W)/ 400 mg CZP sc every 4 weeks (Q4W) from Week 6/ Week 8 onwards. Subjects in both CZP arms received additional placebo injections to maintain the study blind.
Overall Number of Participants Analyzed	136	138	135	273
Least Squares Mean (95% Confidence Interval); Unit of Measure: units on a scale
Pre-defined results	28.92; (13.73 to 44.11)	11.52; (-3.40 to 26.45)	25.05; (9.48 to 40.61)	18.28; (6.34 to 30.23)
Re-analysis results ( n = 123, 130, 123, 253)	0.18; (0.04 to 0.33)	-0.02; (-0.16 to 0.11)	0.09; (-0.05 to 0.23)	0.03; (-0.08 to 0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Randomized Set), CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set)
	Comments	A hierarchical test procedure was applied to protect the overall significance level for the multiplicity of dose groups and endpoints. Conditional on the first test being significant, the second hypothesis was tested with the same alpha level of 5 %. Statistical testing for the following hypotheses was performed only if the previous null hypothesis in the hierarchy was rejected. This is the pre-defined primary analysis.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.203
	Comments	Diff. of CZP 200mg+400mg versus PBO (and corresponding 95% Confidence Interval and p-value) were estimated using an ANCOVA model with treatment, region and prior Tumor Necrosis Factor(TNF)-antagonist exposure as factors & BL mTSS score as a covariate
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference (Net)
	Estimated Value	-10.64
	Confidence Interval	(2-Sided) 95%; -27.05 to 5.77
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.35
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (Randomized Set), CZP 200 mg Q2W (Randomized Set)
	Comments	A hierarchical test procedure was applied to protect the overall significance level for the multiplicity of dose groups and endpoints.Conditional on the 1st test being significant, the 2nd hypothesis was tested with the same alpha level of 5%. Stat. testing for the following hypotheses was performed only if the previous null hypothesis in the hierarchy was rejected Re-analysis approach, restricted to subjects in the RS who have at least 2 x-ray values at scheduled visits (at least 8 wks apart)
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.017
	Comments	Difference of CZP 200 mg versus Placebo (and corresponding 95 % Confidence Interval and p-value) were estimated using an ANCOVA model with treatment, region and prior TNF-antagonist exposure as factors and Baseline mTSS score as a covariate.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference (Net)
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.38 to -0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Randomized Set), CZP 400 mg Q4W (Randomized Set)
	Comments	A hierarchical test procedure was applied to protect the overall significance level for the multiplicity of dose groups and endpoints.Conditional on the 1st test being significant, the 2nd hypothesis was tested with the same alpha level of 5%. Stat. testing for the following hypotheses was performed only if the previous null hypothesis in the hierarchy was rejected Re-analysis approach, restricted to subjects in the RS who have at least 2 x-ray values at scheduled visits (at least 8 wks apart)
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.261
	Comments	Difference of CZP 400 mg versus Placebo (and corresponding 95 % Confidence Interval and p-value) were estimated using an ANCOVA model with treatment, region and prior TNF-antagonist exposure as factors and Baseline mTSS score as a covariate.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference (Net)
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -0.27 to 0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	American College of Rheumatology 20 (ACR20) Response at Week 24
Description	ACR20 responders are those subjects with at least 20 % improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Intention-to-treat dataset was the Randomized Set (RS). RS with non-responder imputation: subjects who withdrew for any reason or placebo subjects who used escape medication are considered as nonresponders from drop out timepoint or when escape therapy was initiated. Subjects with missing data at a visit are non-responders for that visit, too.

Arm/Group Title	Placebo (Randomized Set)	CZP 200 mg Q2W (Randomized Set)	CZP 400 mg Q4W (Randomized Set)
Arm/Group Description:	Matching Placebo to Certolizumab Pegol (CZP) injections from Week 0 to Week 24. Placebo subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group and were re-randomized to either CZP 200 mg Q2W or CZP 400 mg Q4W arm on Week 16. After 24 weeks, all subjects were re-randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W).	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards. Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind.
Overall Number of Participants Analyzed	136	138	135
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	23.5; (16.4 to 30.7)	63.8; (55.7 to 71.8)	56.3; (47.9 to 64.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Randomized Set), CZP 200 mg Q2W (Randomized Set)
	Comments	A hierarchical test procedure was applied to protect the overall significance level for the multiplicity of dose groups and endpoints. Conditional on the first test being significant, the second hypothesis was tested with the same alpha level of 5 %. Statistical testing for the following hypotheses was performed only if the previous null hypothesis in the hierarchy was rejected.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Difference of Certolizumab Pegol 200 mg versus Placebo (and corresponding 95 % Confidence Interval and p-value) were estimated using a standard two-sided Wald asymptotic test with a 5 % alpha level.
	Method	Wald-test, 2-sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	40.2
	Confidence Interval	(2-Sided) 95%; 29.5 to 51.0
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (Randomized Set), CZP 400 mg Q4W (Randomized Set)
	Comments	A hierarchical test procedure was applied to protect the overall significance level for the multiplicity of dose groups and endpoints. Conditional on the first test being significant, the second hypothesis was tested with the same alpha level of 5 %. Statistical testing for the following hypotheses was performed only if the previous null hypothesis in the hierarchy was rejected.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Difference of Certolizumab Pegol 400 mg versus Placebo (and corresponding 95 % Confidence Interval and p-value) were estimated using a standard two-sided Wald asymptotic test with a 5 % alpha level.
	Method	Wald-test, 2-sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	32.8
	Confidence Interval	(2-Sided) 95%; 21.8 to 43.8
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24
Description	The HAQ-DI is a measure of function in Arthritis. There are 20 items in eight categories that represent a comprehensive set of functional activities on a scale from 0 (without difficulty) to 3 (unable to perform without assistance). The category scores are averaged into an overall HAQ-DI from 0 to 3. Scores of 0 to 1 generally represent mild to moderate difficulty, 1 to 2 represent moderate to severe disability, and 2 to 3 indicate severe to very severe disability. A negative value in HAQ-DI change from Baseline indicates an improvement from Baseline. The higher the negative value, the higher the improvement.
Time Frame	From Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Intention-to-treat dataset was the Randomized Set (RS). RS with Last Observation Carried Forward (LOCF): for subjects who withdrew for any reason, or subjects with missing Week 24 measurements, or placebo subjects who used escape medication, last observation prior to early withdrawal or Week 24 or before receiving CZP is carried forward to Week 24.

Arm/Group Title	Placebo (Randomized Set)	CZP 200 mg Q2W (Randomized Set)	CZP 400 mg Q4W (Randomized Set)	CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set)
Arm/Group Description:	Matching Placebo to Certolizumab Pegol (CZP) injections from Week 0 to Week 24. Placebo subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group and were re-randomized to either CZP 200 mg Q2W or CZP 400 mg Q4W arm on Week 16. After 24 weeks, all subjects were re-randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W).	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards. Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind.	This combined group includes subjects of the two treatment arms CZP 200 mg Q2W and CZP 400 mg Q4W used in some analyses. Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W)/ 400 mg CZP sc every 4 weeks (Q4W) from Week 6/ Week 8 onwards. Subjects in both CZP arms received additional placebo injections to maintain the study blind.
Overall Number of Participants Analyzed	136	138	135	273
Least Squares Mean (95% Confidence Interval); Unit of Measure: units on a scale
	-0.19; (-0.29 to -0.09)	-0.54; (-0.64 to -0.44)	-0.46; (-0.56 to -0.36)	-0.50; (-0.58 to -0.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Randomized Set), CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set)
	Comments	A hierarchical test procedure was applied to protect the overall significance level for the multiplicity of dose groups and endpoints. Conditional on the first test being significant, the second hypothesis was tested with the same alpha level of 5 %. Statistical testing for the following hypotheses was performed only if the previous null hypothesis in the hierarchy was rejected.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Difference of CZP 200 mg + 400 mg vs. Placebo (and corresponding 95 % Confidence Interval and p-value) were estimated using an ANCOVA model with treatment, region and prior TNF-antagonist exposure as factors and Baseline HAQ-DI score as a covariate.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference (Net)
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -0.42 to -0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.06
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Psoriasis Area Severity Index (PASI75) Response at Week 24 in the Subgroup of Subjects With Psoriasis (PSO) Involving at Least 3 % Body Surface Area (BSA) at Baseline
Description	The PASI75 response assessments are based on at least 75 % improvement in the PASI score from Baseline. The PASI score is a measure of the average redness, thickness, and scaliness of the psoriatic skin lesions (each graded on a 0 to 4 scale), weighted by the area of involvement.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Intention-to-treat dataset was the Randomized Set (RS). RS with non-responder imputation: subjects who withdrew for any reason or placebo subjects who used escape medication are considered as nonresponders from drop out timepoint or when escape therapy was initiated. Subjects with missing data at a visit are non-responders for that visit, too.

Arm/Group Title	Placebo (Randomized Set)	CZP 200 mg Q2W (Randomized Set)	CZP 400 mg Q4W (Randomized Set)	CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set)
Arm/Group Description:	Matching Placebo to Certolizumab Pegol (CZP) injections from Week 0 to Week 24. Placebo subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group and were re-randomized to either CZP 200 mg Q2W or CZP 400 mg Q4W arm on Week 16. After 24 weeks, all subjects were re-randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W).	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards. Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind.	This combined group includes subjects of the two treatment arms CZP 200 mg Q2W and CZP 400 mg Q4W used in some analyses. Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W)/ 400 mg CZP sc every 4 weeks (Q4W) from Week 6/ Week 8 onwards. Subjects in both CZP arms received additional placebo injections to maintain the study blind.
Overall Number of Participants Analyzed	86	90	76	166
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	15.1; (7.5 to 22.7)	62.2; (52.2 to 72.2)	60.5; (49.5 to 71.5)	61.4; (54.0 to 68.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Randomized Set), CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set)
	Comments	A hierarchical test procedure was applied to protect the overall significance level for the multiplicity of dose groups and endpoints. Conditional on the first test being significant, the second hypothesis was tested with the same alpha level of 5 %. Statistical testing for the following hypotheses was performed only if the previous null hypothesis in the hierarchy was rejected.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Difference of Certolizumab Pegol 200 mg + 400 mg versus Placebo (and corresponding 95 % Confidence Interval and p-value) were estimated using a standard two-sided Wald asymptotic test with a 5 % alpha level.
	Method	Wald-test, 2-sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	46.3
	Confidence Interval	(2-Sided) 95%; 35.7 to 56.9
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Change From Baseline in Modified Total Sharp Score (mTSS) at Week 48
Description	Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 64 and 52 joints, respectively, with higher scores representing greater damage. mTSS (bone erosions) ranges from 0 (best possible outcome) to 320 (worst possible outcome); mTSS (joint space narrowing) ranges from 0 (best possible outcome) to 208 (worst possible outcome); and total score ranges from 0 (best possible outcome) to 528 (worst possible outcome). For the analysis of this outcome measure, the change from Baseline to Week 48 was imputed using the median change from Baseline among all subjects for those subjects, which had less than 2 radiographs. The post-hoc analysis presented here is based on the subgroup of subjects which had a Baseline mTSS value greater than 6.
Time Frame	From Baseline to Week 48

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) with imputation: for subjects who withdrew for any reason, or subjects with missing Week 48 measurements, and for all placebo subjects after the switch to CZP, Week 48 scores are linearly extrapolated from the last two available radiographs prior to early withdrawal or Week 24 or before receiving CZP.

Arm/Group Title	Placebo (Randomized Set)	CZP 200 mg Q2W (Randomized Set)	CZP 400 mg Q4W (Randomized Set)	CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set)
Arm/Group Description:	Matching Placebo to Certolizumab Pegol (CZP) injections from Week 0 to Week 24. Placebo subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group and were re-randomized to either CZP 200 mg Q2W or CZP 400 mg Q4W arm on Week 16. After 24 weeks, all subjects were re-randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W).	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.	Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards. Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind.	This combined group includes subjects of the two treatment arms CZP 200 mg Q2W and CZP 400 mg Q4W used in some analyses. Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W)/ 400 mg CZP sc every 4 weeks (Q4W) from Week 6/ Week 8 onwards. Subjects in both CZP arms received additional placebo injections to maintain the study blind.
Overall Number of Participants Analyzed	136	138	135	273
Least Squares Mean (95% Confidence Interval); Unit of Measure: units on a scale
Predefined results: Overall	0.32; (0.10 to 0.55)	0.15; (-0.07 to 0.37)	0.11; (-0.12 to 0.34)	0.13; (-0.05 to 0.31)
Post-hoc results: Basel. mTSS > 6 (n=61,65,65,130)	0.78; (0.31 to 1.25)	0.31; (-0.15 to 0.77)	0.22; (-0.24 to 0.67)	0.26; (-0.09 to 0.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Randomized Set), CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set)
	Comments	A hierarchical test procedure was applied to protect the overall significance level for the multiplicity of dose groups and endpoints. Conditional on the first test being significant, the second hypothesis was tested with the same alpha level of 5 %. Statistical testing for the following hypotheses was performed only if the previous null hypothesis in the hierarchy was rejected. This is the predefined analysis.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.127
	Comments	Difference of CZP 200 mg + 400 mg versus Placebo (and corresponding 95 % Confidence Interval and p-value) were estimated using an ANCOVA model with treatment, region and prior TNF-antagonist exposure as factors and Baseline mTSS score as a covariate.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference (Net)
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.43 to 0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (Randomized Set), CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set)
	Comments	A hierarchical test procedure was applied to protect the overall significance level for the multiplicity of dose groups and endpoints. Conditional on the first test being significant, the second hypothesis was tested with the same alpha level of 5 %. Statistical testing for the following hypotheses was performed only if the previous null hypothesis in the hierarchy was rejected. This is the post-hoc analysis for the subgroup 'Baseline mTSS > 6'.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.048
	Comments	Difference of CZP 200 mg + 400 mg versus Placebo (and corresponding 95 % Confidence Interval and p-value) were estimated using an ANCOVA model with treatment, region and prior TNF-antagonist exposure as factors and Baseline mTSS score as a covariate.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference (Net)
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -1.04 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216.
Adverse Event Reporting Description	As per study design, placebo (PBO) arm subjects shifted either at Week (Wk) 16 or 24 to CZP treatment. Thus, PBO arm had lower exposure compared to the CZP arms. The exposure imbalance across treatment arms could lead to misinterpretation & questionable conclusions comparing simple counts & percentages of AEs. Thus, AEs reported while the patient was on PBO-treatment are not included.
Arm/Group Title	All CZP 200 mg Q2W		All CZP 400 mg Q4W		All CZP 200 mg + 400 mg
Arm/Group Description	This arm includes all subjects who were randomized to CZP 200 mg Q2W at Baseline and those subjects who escaped or were re-randomized from Placebo to CZP 200 mg Q2W. Subjects received one injection of 200 mg CZP and one injection of Placebo every two weeks to maintain the study blind.		This arm includes all subjects who were randomized to CZP 400 mg Q4W at Baseline and those subjects who escaped or were re-randomized from Placebo to CZP 400 mg Q4W. Subjects received two injections of Placebo every four weeks in between the two injections of 200 mg CZP to maintain the study blind.		This arm shows all patients treated with Certolizumab Pegol (CZP) at least once. Hence, this arm is a combination of arm All CZP 200 mg Q2W and arm All CZP 400 mg Q4W.
All-Cause Mortality
	All CZP 200 mg Q2W		All CZP 400 mg Q4W		All CZP 200 mg + 400 mg
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	All CZP 200 mg Q2W		All CZP 400 mg Q4W		All CZP 200 mg + 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/198 (24.75%)		51/195 (26.15%)		100/393 (25.45%)
Blood and lymphatic system disorders
Splenomegaly * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Thrombocytopenia * 1	0/198 (0.00%)	0	1/195 (0.51%)	2	1/393 (0.25%)	2
Cardiac disorders
Coronary artery thrombosis * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Angina unstable * 1	1/198 (0.51%)	1	1/195 (0.51%)	1	2/393 (0.51%)	2
Myocardial infarction * 1	2/198 (1.01%)	2	0/195 (0.00%)	0	2/393 (0.51%)	2
Acute myocardial infarction * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Myocarditis * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Atrial fibrillation * 1	1/198 (0.51%)	1	1/195 (0.51%)	1	2/393 (0.51%)	2
Cardiac arrest * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Ear and labyrinth disorders
Tinnitus * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Eye disorders
Cataract * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Diplopia * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Gastrointestinal disorders
Abdominal hernia * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Pancreatitis acute * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Abdominal pain * 1	1/198 (0.51%)	2	0/195 (0.00%)	0	1/393 (0.25%)	2
Crohn's disease * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Hypoaesthesia oral * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
General disorders
Sudden death * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Pyrexia * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Chest pain * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Hepatobiliary disorders
Biliary colic * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Cholelithiasis * 1	1/198 (0.51%)	1	2/195 (1.03%)	2	3/393 (0.76%)	3
Cholecystitis * 1	0/198 (0.00%)	0	2/195 (1.03%)	2	2/393 (0.51%)	2
Biliary dyskinesia * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Bile duct obstruction * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Infections and infestations
Diverticulitis * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Cellulitis * 1	2/198 (1.01%)	2	0/195 (0.00%)	0	2/393 (0.51%)	2
Arthritis bacterial * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Herpes zoster * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Device related infection * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Postoperative wound infection * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Pneumonia * 1	1/198 (0.51%)	1	3/195 (1.54%)	4	4/393 (1.02%)	5
Bronchitis * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Bronchopneumonia * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
HIV infection * 1	1/198 (0.51%)	1	1/195 (0.51%)	1	2/393 (0.51%)	2
Sepsis * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Staphylococcal abscess * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Erysipelas * 1	2/198 (1.01%)	2	0/195 (0.00%)	0	2/393 (0.51%)	2
Pyoderma streptococcal * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Latent tuberculosis * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Upper respiratory tract infection * 1	1/198 (0.51%)	1	1/195 (0.51%)	1	2/393 (0.51%)	2
Chronic tonsillitis * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Urinary tract infection * 1	1/198 (0.51%)	1	2/195 (1.03%)	2	3/393 (0.76%)	3
Pyelonephritis * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Pyelonephritis acute * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Injury, poisoning and procedural complications
Concussion * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Joint injury * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Synovial rupture * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Foot fracture * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Lower limb fracture * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Tendon rupture * 1	0/198 (0.00%)	0	2/195 (1.03%)	2	2/393 (0.51%)	2
Animal bite * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Wound * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Anastomotic complication * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Hand fracture * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Investigations
Hepatic enzyme increased * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Metabolism and nutrition disorders
Diabetes mellitus * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Obesity * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Hyperglycaemia * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Dehydration * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Musculoskeletal and connective tissue disorders
Arthritis * 1	2/198 (1.01%)	2	1/195 (0.51%)	1	3/393 (0.76%)	3
Foot deformity * 1	0/198 (0.00%)	0	2/195 (1.03%)	2	2/393 (0.51%)	2
Lupus-like syndrome * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Osteoarthritis * 1	1/198 (0.51%)	1	3/195 (1.54%)	3	4/393 (1.02%)	4
Psoriatic arthropathy * 1	5/198 (2.53%)	5	3/195 (1.54%)	7	8/393 (2.04%)	12
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer * 1	1/198 (0.51%)	1	2/195 (1.03%)	2	3/393 (0.76%)	3
Gastrointestinal cancer metastatic * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Lymphoma * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Ovarian cancer * 1	1/198 (0.51%)	2	0/195 (0.00%)	0	1/393 (0.25%)	2
Benign neoplasm of thyroid gland * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Nervous system disorders
Cerebrovascular accident * 1	1/198 (0.51%)	1	1/195 (0.51%)	1	2/393 (0.51%)	2
Dysgraphia * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Syncope * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Formication * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Paralysis * 1	1/198 (0.51%)	2	0/195 (0.00%)	0	1/393 (0.25%)	2
Epilepsy * 1	0/198 (0.00%)	0	1/195 (0.51%)	2	1/393 (0.25%)	2
Hypoaesthesia * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Speech disorder * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Transient ischaemic attack * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Pregnancy, puerperium and perinatal conditions
Pregnancy * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Pregnancy on contraceptive * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Psychiatric disorders
Bipolar I disorder * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Acute stress disorder * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Post-traumatic stress disorder * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Renal and urinary disorders
Urinary incontinence * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Renal cyst * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Calculus ureteric * 1	0/198 (0.00%)	0	2/195 (1.03%)	2	2/393 (0.51%)	2
Renal colic * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Reproductive system and breast disorders
Metrorrhagia * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Genital prolapse * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Uterine haemorrhage * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Uterine polyp * 1	0/198 (0.00%)	0	2/195 (1.03%)	2	2/393 (0.51%)	2
Vulvar dysplasia * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Haemoptysis * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Lung infiltration * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Pleurisy * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Pulmonary embolism * 1	3/198 (1.52%)	3	0/195 (0.00%)	0	3/393 (0.76%)	3
Skin and subcutaneous tissue disorders
Cutaneous lupus erythematosus * 1	1/198 (0.51%)	2	0/195 (0.00%)	0	1/393 (0.25%)	2
Skin ulcer * 1	3/198 (1.52%)	4	1/195 (0.51%)	1	4/393 (1.02%)	5
Social circumstances
Pregnancy of partner * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Surgical and medical procedures
Hip arthroplasty * 1	0/198 (0.00%)	0	1/195 (0.51%)	1	1/393 (0.25%)	1
Vascular disorders
Haematoma * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
Thrombophlebitis * 1	1/198 (0.51%)	1	1/195 (0.51%)	1	2/393 (0.51%)	2
Deep vein thrombosis * 1	1/198 (0.51%)	1	0/195 (0.00%)	0	1/393 (0.25%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA14.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	All CZP 200 mg Q2W		All CZP 400 mg Q4W		All CZP 200 mg + 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	158/198 (79.80%)		153/195 (78.46%)		311/393 (79.13%)
Gastrointestinal disorders
Diarrhoea * 1	15/198 (7.58%)	20	11/195 (5.64%)	15	26/393 (6.62%)	35
Abdominal pain * 1	12/198 (6.06%)	13	9/195 (4.62%)	10	21/393 (5.34%)	23
Abdominal pain upper * 1	14/198 (7.07%)	16	5/195 (2.56%)	9	19/393 (4.83%)	25
Nausea * 1	10/198 (5.05%)	11	8/195 (4.10%)	9	18/393 (4.58%)	20
Infections and infestations
Upper respiratory tract infection * 1	44/198 (22.22%)	81	49/195 (25.13%)	73	93/393 (23.66%)	154
Nasopharyngitis * 1	45/198 (22.73%)	87	42/195 (21.54%)	91	87/393 (22.14%)	178
Pharyngitis * 1	24/198 (12.12%)	44	27/195 (13.85%)	37	51/393 (12.98%)	81
Bronchitis * 1	28/198 (14.14%)	36	22/195 (11.28%)	29	50/393 (12.72%)	65
Urinary tract infection * 1	13/198 (6.57%)	18	26/195 (13.33%)	35	39/393 (9.92%)	53
Sinusitis * 1	19/198 (9.60%)	32	13/195 (6.67%)	33	32/393 (8.14%)	65
Gastroenteritis * 1	14/198 (7.07%)	18	8/195 (4.10%)	8	22/393 (5.60%)	26
Oral herpes * 1	10/198 (5.05%)	25	11/195 (5.64%)	18	21/393 (5.34%)	43
Influenza * 1	13/198 (6.57%)	15	8/195 (4.10%)	9	21/393 (5.34%)	24
Tonsillitis * 1	11/198 (5.56%)	11	8/195 (4.10%)	12	19/393 (4.83%)	23
Rhinitis * 1	10/198 (5.05%)	11	9/195 (4.62%)	9	19/393 (4.83%)	20
Latent tuberculosis * 1	6/198 (3.03%)	6	12/195 (6.15%)	12	18/393 (4.58%)	18
Viral infection * 1	9/198 (4.55%)	12	7/195 (3.59%)	7	16/393 (4.07%)	19
Injury, poisoning and procedural complications
Contusion * 1	15/198 (7.58%)	21	9/195 (4.62%)	10	24/393 (6.11%)	31
Investigations
Alanine aminotransferase increased * 1	17/198 (8.59%)	23	15/195 (7.69%)	25	32/393 (8.14%)	48
Blood creatine phosphokinase increased * 1	15/198 (7.58%)	28	13/195 (6.67%)	25	28/393 (7.12%)	53
Aspartate aminotransferase increased * 1	9/198 (4.55%)	13	11/195 (5.64%)	17	20/393 (5.09%)	30
Gamma-glutamyltransferase increased * 1	8/198 (4.04%)	11	12/195 (6.15%)	15	20/393 (5.09%)	26
Musculoskeletal and connective tissue disorders
Back pain * 1	24/198 (12.12%)	28	22/195 (11.28%)	26	46/393 (11.70%)	54
Psoriatic arthropathy * 1	24/198 (12.12%)	41	15/195 (7.69%)	23	39/393 (9.92%)	64
Arthralgia * 1	20/198 (10.10%)	28	18/195 (9.23%)	28	38/393 (9.67%)	56
Nervous system disorders
Headache * 1	18/198 (9.09%)	19	17/195 (8.72%)	20	35/393 (8.91%)	39
Dizziness * 1	5/198 (2.53%)	5	10/195 (5.13%)	10	15/393 (3.82%)	15
Psychiatric disorders
Depression * 1	11/198 (5.56%)	12	9/195 (4.62%)	12	20/393 (5.09%)	24
Respiratory, thoracic and mediastinal disorders
Cough * 1	8/198 (4.04%)	9	14/195 (7.18%)	14	22/393 (5.60%)	23
Oropharyngeal pain * 1	6/198 (3.03%)	6	10/195 (5.13%)	13	16/393 (4.07%)	19
Skin and subcutaneous tissue disorders
Psoriasis * 1	22/198 (11.11%)	31	19/195 (9.74%)	21	41/393 (10.43%)	52
Rash * 1	10/198 (5.05%)	16	9/195 (4.62%)	9	19/393 (4.83%)	25
Vascular disorders
Hypertension * 1	30/198 (15.15%)	33	16/195 (8.21%)	20	46/393 (11.70%)	53
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA14.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

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

Results Point of Contact

• Name/Title: UCB
• Organization: Cares
• Phone: +1877 822 ext 9493

Publications of Results:

Mease PJ, Fleischmann R, Deodhar AA, Wollenhaupt J, Khraishi M, Kielar D, Woltering F, Stach C, Hoepken B, Arledge T, van der Heijde D. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis. 2014 Jan;73(1):48-55. doi: 10.1136/annrheumdis-2013-203696. Epub 2013 Aug 13.

van der Heijde D, Fleischmann R, Wollenhaupt J, Deodhar A, Kielar D, Woltering F, Stach C, Hoepken B, Arledge T, Mease PJ. Effect of different imputation approaches on the evaluation of radiographic progression in patients with psoriatic arthritis: results of the RAPID-PsA 24-week phase III double-blind randomised placebo-controlled study of certolizumab pegol. Ann Rheum Dis. 2014 Jan;73(1):233-7. doi: 10.1136/annrheumdis-2013-203697. Epub 2013 Aug 13.

van der Heijde D, Deodhar A, FitzGerald O, Fleischmann R, Gladman D, Gottlieb AB, Hoepken B, Bauer L, Irvin-Sellers O, Khraishi M, Peterson L, Turkiewicz A, Wollenhaupt J, Mease PJ. 4-year results from the RAPID-PsA phase 3 randomised placebo-controlled trial of certolizumab pegol in psoriatic arthritis. RMD Open. 2018 Mar 14;4(1):e000582. doi: 10.1136/rmdopen-2017-000582. eCollection 2018. Erratum In: RMD Open. 2018 Mar 26;4(1):

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Walsh JA, Gottlieb AB, Hoepken B, Nurminen T, Mease PJ. Efficacy of certolizumab pegol with and without concomitant use of disease-modifying anti-rheumatic drugs over 4 years in psoriatic arthritis patients: results from the RAPID-PsA randomized controlled trial. Clin Rheumatol. 2018 Dec;37(12):3285-3296. doi: 10.1007/s10067-018-4227-7. Epub 2018 Sep 6. Erratum In: Clin Rheumatol. 2018 Oct 11;:

van der Heijde D, Deodhar A, Fleischmann R, Mease PJ, Rudwaleit M, Nurminen T, Davies O. Early Disease Activity or Clinical Response as Predictors of Long-Term Outcomes With Certolizumab Pegol in Axial Spondyloarthritis or Psoriatic Arthritis. Arthritis Care Res (Hoboken). 2017 Jul;69(7):1030-1039. doi: 10.1002/acr.23092. Epub 2017 Jun 2.

Osterhaus JT, Purcaru O. Discriminant validity, responsiveness and reliability of the arthritis-specific Work Productivity Survey assessing workplace and household productivity in patients with psoriatic arthritis. Arthritis Res Ther. 2014 Jul 4;16(4):R140. doi: 10.1186/ar4602.

Kavanaugh A, Gladman D, van der Heijde D, Purcaru O, Mease P. Improvements in productivity at paid work and within the household, and increased participation in daily activities after 24 weeks of certolizumab pegol treatment of patients with psoriatic arthritis: results of a phase 3 double-blind randomised placebo-controlled study. Ann Rheum Dis. 2015 Jan;74(1):44-51. doi: 10.1136/annrheumdis-2014-205198. Epub 2014 Jun 18.

Gladman D, Fleischmann R, Coteur G, Woltering F, Mease PJ. Effect of certolizumab pegol on multiple facets of psoriatic arthritis as reported by patients: 24-week patient-reported outcome results of a phase III, multicenter study. Arthritis Care Res (Hoboken). 2014 Jul;66(7):1085-92. doi: 10.1002/acr.22256.

• Responsible Party: UCB Pharma ( UCB BIOSCIENCES GmbH )
• ClinicalTrials.gov Identifier: NCT01087788
• Other Study ID Numbers: PsA001; 2009-011720-59 ( EudraCT Number )
• First Submitted: March 15, 2010
• First Posted: March 16, 2010
• Results First Submitted: October 25, 2013
• Results First Posted: February 25, 2014
• Last Update Posted: August 1, 2018