Trial record 1 of 1 for: NCT01087762

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Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis

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ClinicalTrials.gov Identifier: NCT01087762

Recruitment Status : Completed

First Posted : March 16, 2010

Results First Posted : December 25, 2013

Last Update Posted : August 1, 2018

View this study on Beta.ClinicalTrials.gov

Sponsor:

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	Spondyloarthropathies
Interventions	Biological: CZP 200 mg Q2W Biological: CZP 400 mg Q4W Other: Placebo
Enrollment	325

Participant Flow

Recruitment Details	This is a multicenter study with 128 sites in North America, Latin America, Western Europe, and Central/Eastern Europe. 325 subjects are included in Randomized Set (RS) shown in Participant Flow for the interim period, and 315 for the final analysis (10 subjects dropped out before receiving a CZP dose), which is an Intention-to-Treat (ITT) dataset.
Pre-assignment Details	Patients with positive Tuberculosis (TB) tests within Screening Period, but no signs and symptoms of active TB had to be treated with prophylactic TB treatment for at least 4 weeks prior to first study drug administration.


Arm/Group Title	Placebo	CZP 200 mg Q2W	CZP 400 mg Q4W	All CZP 200 mg	All CZP 400 mg
Arm/Group Description	Matching Placebo to Certolizumab Pe...	Subjects received Certolizumab Pego...	Subjects received Certolizumab Pego...	All subjects who received CZP at th...	All subjects who received CZP at th...
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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.	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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	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. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).	All subjects who received CZP at the specified dose (200 mg) at some point during the study, including subjects who were originally randomized to receive placebo and were switched to CZP at Week 16 or Week 24. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	All subjects who received CZP at the specified dose (400 mg) at some point during the study, including subjects who were originally randomized to receive placebo and were switched to CZP at Week 16 or Week 24. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).
Period Title: Double Blind Period (Weeks 0-24)
Started	107 ^[1]	111 ^[1]	107 ^[1]	0	0
Completed	95	105	98	0	0
Not Completed	12	6	9	0	0
Reason Not Completed
Lack of Efficacy	2	0	3	0	0
Protocol Violation	6	0	1	0	0
Lost to Follow-up	1	2	1	0	0
Withdrawal by Subject	1	2	1	0	0
SAE, non-fatal	2	2	3	0	0
[1] Completed 24-weeks Double-blind Period
Period Title: Open-Label Period (Weeks 48-204)
Started	0	0	0	158	157
Completed	0	0	0	99	100
Not Completed	0	0	0	59	57
Reason Not Completed
Lack of Efficacy	0	0	0	4	14
Protocol Violation	0	0	0	1	1
Lost to Follow-up	0	0	0	5	2
Withdrawal by Subject	0	0	0	22	15
Other	0	0	0	2	4
SAE, non-fatal	0	0	0	7	4
AE, non-serious non-fatal	0	0	0	16	13
SAE, non-fatal + AE, non-serious/fatal	0	0	0	2	4

Baseline Characteristics

Arm/Group Title		Placebo	CZP 200 mg Q2W	CZP 400 mg Q4W	Total Title
Arm/Group Description		Matching Placebo to Certolizumab Pe...	Subjects received Certolizumab Pego...	Subjects received Certolizumab Pego...	[Not Specified]
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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.	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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	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. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).	[Not Specified]
Overall Number of Baseline Participants		107	111	107	325
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Baseline Characteristics refer to the Randomized Set (RS), which is an Intention-to-Treat (ITT) dataset.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	107 participants	111 participants	107 participants	325 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	102 95.3%	110 99.1%	105 98.1%	317 97.5%
	>=65 years	5 4.7%	1 0.9%	2 1.9%	8 2.5%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
Mean age	Number Analyzed	107 participants	111 participants	107 participants	325 participants
Mean age		39.9 (12.4)	39.1 (11.9)	39.8 (39.9)	39.6 (11.9)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	107 participants	111 participants	107 participants	325 participants
	Female	42 39.3%	44 39.6%	39 36.4%	125 38.5%
	Male	65 60.7%	67 60.4%	68 63.6%	200 61.5%
Weight Mean (Standard Deviation) Unit of measure: Kilogram (kg)
	Number Analyzed	107 participants	111 participants	107 participants	325 participants
		82.142 (18.147)	79.305 (18.599)	83.893 (18.855)	81.757 (18.576)
Height Mean (Standard Deviation) Unit of measure: Centimeter (cm)
	Number Analyzed	107 participants	111 participants	107 participants	325 participants
		170.704 (9.692)	171.769 (10.171)	172.753 (9.607)	171.739 (9.834)

Outcome Measures

1.Primary Outcome


Title	Assessment in Axial Spondyloarthritis International Society 20 % (ASAS20) Response Criteria at Week 12
Description	The ASAS20 is defined as an improvement of at least 20 % and absolute ...
Description	The ASAS20 is defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 following domains: Patient's Global Assessment of Disease Activity Pain assessment (total spinal pain) Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain (deterioration is defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit).
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 non-responders 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 (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q4W (FAS)	CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
Arm/Group Description:	Matching Placebo to Certolizumab Pe...	Subjects received Certolizumab Pego...	Subjects received Certolizumab Pego...	This arm shows a combination of arm...
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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.	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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	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. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).	This arm shows a combination of arm CZP 200 mg Q2W and arm CZP 400 mg 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)/ 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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).
Overall Number of Participants Analyzed	107	111	107	218
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	38.3 (29.1 to 47.5)	57.7 (48.5 to 66.8)	63.6 (54.4 to 72.7)	60.6 (54.1 to 67.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	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	=0.004
	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	Wald test and Confidence Interval (CI) calculation were performed without continuity correction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	19.3
	Confidence Interval	(2-Sided) 95% 6.3 to 32.4
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 400 mg Q4W (FAS)
	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	Wald test and Confidence Interval (CI) calculation were performed without continuity correction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	25.2
	Confidence Interval	(2-Sided) 95% 12.3 to 38.2
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Assessment in Axial Spondyloarthritis International Society 20 % (ASAS20) Response Criteria at Week 24
Description	The ASAS20 is defined as an improvement of at least 20 % and absolute ...
Description	The ASAS20 is defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 following domains: Patient's Global Assessment of Disease Activity Pain assessment (total spinal pain) Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain (deterioration is defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q4W (FAS)	CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
Arm/Group Description:	Matching Placebo to Certolizumab Pe...	Subjects received Certolizumab Pego...	Subjects received Certolizumab Pego...	This arm shows a combination of arm...
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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.	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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	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. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).	This arm shows a combination of arm CZP 200 mg Q2W and arm CZP 400 mg 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)/ 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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).
Overall Number of Participants Analyzed	107	111	107	218
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	29.0 (20.4 to 37.6)	66.7 (57.9 to 75.4)	70.1 (61.4 to 78.8)	68.3 (62.2 to 74.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W (FAS)
	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	Wald test and Confidence Interval (CI) calculation were performed without continuity correction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	37.7
	Confidence Interval	(2-Sided) 95% 25.4 to 50.0
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 400 mg Q4W (FAS)
	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	Wald test and Confidence Interval (CI) calculation were performed without continuity correction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	41.1
	Confidence Interval	(2-Sided) 95% 28.9 to 53.3
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Change From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 12
Description	The BASFI assesses physical function in comprising 10 items relating t...
Description	The BASFI assesses physical function in comprising 10 items relating to activities during the past week. Each item ranges from 0 ("Easy") to 10 ("Impossible"). The BASFI is the mean of the 10 scores such that the total score ranges from 0 to 10, with lower scores indicating better physical function. A negative value in BASFI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time Frame	From Baseline to Week 12

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 12 measurements, last observation prior to the early withdrawal or Week 12 is carried forward to Week 12.


Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q4W (FAS)	CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
Arm/Group Description:	Matching Placebo to Certolizumab Pe...	Subjects received Certolizumab Pego...	Subjects received Certolizumab Pego...	This arm shows a combination of arm...
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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.	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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	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. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).	This arm shows a combination of arm CZP 200 mg Q2W and arm CZP 400 mg 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)/ 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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).
Overall Number of Participants Analyzed	107	111	107	218
Least Squares Mean (95% Confidence Interval) Unit of Measure: units on a scale
	-0.53 (-0.96 to -0.10)	-2.01 (-2.48 to -1.55)	-2.02 (-2.50 to -1.55)	-2.02 (-2.40 to -1.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
	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 was estimated using an ANCOVA model with treatment, region, modified New York criteria and prior TNF-antagonist exposure as factors and Baseline BASFI score as a covariate.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.49
	Confidence Interval	(2-Sided) 95% -1.96 to -1.01
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.24
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Change From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24
Description	The BASFI assesses physical function in comprising 10 items relating t...
Description	The BASFI assesses physical function in comprising 10 items relating to activities during the past week. Each item ranges from 0 ("Easy") to 10 ("Impossible"). The BASFI is the mean of the 10 scores such that the total score ranges from 0 to 10, with lower scores indicating better physical function. A negative value in BASFI change from Baseline indicates an improvement from Baseline. The higher the negative value the better 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 (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q4W (FAS)	CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
Arm/Group Description:	Matching Placebo to Certolizumab Pe...	Subjects received Certolizumab Pego...	Subjects received Certolizumab Pego...	This arm shows a combination of arm...
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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.	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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	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. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).	This arm shows a combination of arm CZP 200 mg Q2W and arm CZP 400 mg 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)/ 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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).
Overall Number of Participants Analyzed	107	111	107	218
Least Squares Mean (95% Confidence Interval) Unit of Measure: units on a scale
	-0.40 (-0.85 to 0.06)	-2.36 (-2.85 to -1.87)	-2.20 (-2.70 to -1.70)	-2.28 (-2.68 to -1.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
	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 was estimated using an ANCOVA model with treatment, region, modified New York criteria and prior TNF-antagonist exposure as factors and Baseline BASFI score as a covariate.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.88
	Confidence Interval	(2-Sided) 95% -2.38 to -1.38
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.25
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 12
Description	The BASDAI is a validated self-reported instrument which consists of s...
Description	The BASDAI is a validated self-reported instrument which consists of six 10 unit horizontal Numerical Rating Scales (NRSs) to measure severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration, respectively) over the last week. The final BASDAI score ranges from 0 to 10, with lower scores indicating lower disease activity. A negative value in BASDAI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q4W (FAS)	CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
Arm/Group Description:	Matching Placebo to Certolizumab Pe...	Subjects received Certolizumab Pego...	Subjects received Certolizumab Pego...	This arm shows a combination of arm...
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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.	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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	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. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).	This arm shows a combination of arm CZP 200 mg Q2W and arm CZP 400 mg 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)/ 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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).
Overall Number of Participants Analyzed	107	111	107	218
Least Squares Mean (95% Confidence Interval) Unit of Measure: units on a scale
	-1.22 (-1.65 to -0.78)	-2.82 (-3.29 to -2.35)	-2.80 (-3.28 to -2.33)	-2.81 (-3.20 to -2.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
	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 was estimated using an ANCOVA model with treatment, region, modified New York criteria and prior TNF-antagonist exposure as factors and Baseline BASDAI score as a covariate.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.60
	Confidence Interval	(2-Sided) 95% -2.07 to -1.12
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.24
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24
Description	The BASDAI is a validated self-reported instrument which consists of s...
Description	The BASDAI is a validated self-reported instrument which consists of six 10 unit horizontal Numerical Rating Scales (NRSs) to measure severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration, respectively) over the last week. The final BASDAI score ranges from 0 to 10, with lower scores indicating lower disease activity. A negative value in BASDAI change from Baseline indicates an improvement from Baseline. The higher the negative value the better 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 (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q4W (FAS)	CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
Arm/Group Description:	Matching Placebo to Certolizumab Pe...	Subjects received Certolizumab Pego...	Subjects received Certolizumab Pego...	This arm shows a combination of arm...
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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.	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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	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. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).	This arm shows a combination of arm CZP 200 mg Q2W and arm CZP 400 mg 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)/ 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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).
Overall Number of Participants Analyzed	107	111	107	218
Least Squares Mean (95% Confidence Interval) Unit of Measure: units on a scale
	-1.05 (-1.50 to -0.60)	-3.08 (-3.57 to -2.60)	-3.01 (-3.50 to -2.52)	-3.05 (-3.45 to -2.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
	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 was estimated using an ANCOVA model with treatment, region, modified New York criteria and prior TNF-antagonist exposure as factors and Baseline BASDAI score as a covariate.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.99
	Confidence Interval	(2-Sided) 95% -2.49 to -1.50
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.25
	Estimation Comments	[Not Specified]

7.Secondary Outcome


Title	Change From Baseline in the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 12
Description	The BASMI characterizes the spinal mobility of subjects with axial Spo...
Description	The BASMI characterizes the spinal mobility of subjects with axial Spondyloarthritis (SpA) and Ankylosing Spondylitis (AS). It is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 is calculated for each item based on the measurement. The mean of the sum of the 5 scores provides the BASMI score. The higher the BASMI score the more severe the patient's limitation of movement due to their axial SpA. A negative value in BASMI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q4W (FAS)	CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
Arm/Group Description:	Matching Placebo to Certolizumab Pe...	Subjects received Certolizumab Pego...	Subjects received Certolizumab Pego...	This arm shows a combination of arm...
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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.	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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	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. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).	This arm shows a combination of arm CZP 200 mg Q2W and arm CZP 400 mg 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)/ 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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).
Overall Number of Participants Analyzed	107	111	107	218
Least Squares Mean (95% Confidence Interval) Unit of Measure: units on a scale
	-0.13 (-0.31 to 0.05)	-0.60 (-0.79 to -0.40)	-0.46 (-0.66 to -0.26)	-0.53 (-0.69 to -0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
	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 was estimated using an ANCOVA model with treatment, region, modified New York criteria and prior TNF-antagonist exposure as factors and Baseline BASMI score as a covariate.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95% -0.60 to -0.20
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.10
	Estimation Comments	[Not Specified]

8.Secondary Outcome


Title	Change From Baseline in the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 24
Description	The BASMI characterizes the spinal mobility of subjects with axial SpA...
Description	The BASMI characterizes the spinal mobility of subjects with axial SpA and AS. It is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 is calculated for each item based on the measurement. The mean of the sum of the 5 scores provides the BASMI score. The higher the BASMI score the more severe the patient's limitation of movement due to their axial SpA. A negative value in BASMI change from Baseline indicates an improvement from Baseline. The higher the negative value the better 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 (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q4W (FAS)	CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
Arm/Group Description:	Matching Placebo to Certolizumab Pe...	Subjects received Certolizumab Pego...	Subjects received Certolizumab Pego...	This arm shows a combination of arm...
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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.	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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	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. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).	This arm shows a combination of arm CZP 200 mg Q2W and arm CZP 400 mg 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)/ 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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).
Overall Number of Participants Analyzed	107	111	107	218
Least Squares Mean (95% Confidence Interval) Unit of Measure: units on a scale
	-0.07 (-0.27 to 0.12)	-0.54 (-0.75 to -0.34)	-0.49 (-0.70 to -0.28)	-0.52 (-0.69 to -0.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
	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 was estimated using an ANCOVA model with treatment, region, modified New York criteria and prior TNF-antagonist exposure as factors and Baseline BASMI score as a covariate.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 95% -0.66 to -0.23
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.11
	Estimation Comments	[Not Specified]

9.Secondary Outcome


Title	Change From Baseline in the Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging (MRI) Scoring System for Disease Activity (ASspiMRI-a) in the Berlin Modification at Week 12
Description	The Berlin modification of the ASspiMRI-a is a scoring system with a c...
Description	The Berlin modification of the ASspiMRI-a is a scoring system with a concentration on Short-Tau-Inversion Recovery (STIR) sequences without other fat saturation techniques. It quantifies changes in 23 Vertebral Units (VU) of the spine. A VU is defined as the region between 2 virtual lines through the middle of each vertebra. Active inflammation is scored by grading the degree of bone marrow edema from 0 to 3 in 1 dimension on 1 or more consecutive slices that represent the highest level of inflammation in a particular VU. Total spine ASspiMRI-a score in the Berlin modification can range from 0 to 69 with higher scores indicating higher disease activity. A negative value in total spine ASspiMRI-a score change from Baseline indicates an improvement from Baseline. The higher the negative value the higher the reduction of inflammation.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed in the Magnetic Resonance Imaging (MRI) Set, a subgroup of subjects participating in an imaging substudy, where MRI measurements at Baseline and Week 12 were performed. Of the 325 patients randomized, 153 participated in the imaging substudy. Of these 153 subjects in the MRI Set, 148 are included in this analysis.


Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q4W (FAS)	CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
Arm/Group Description:	Matching Placebo to Certolizumab Pe...	Subjects received Certolizumab Pego...	Subjects received Certolizumab Pego...	This arm shows a combination of arm...
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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.	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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	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. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).	This arm shows a combination of arm CZP 200 mg Q2W and arm CZP 400 mg 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)/ 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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).
Overall Number of Participants Analyzed	49	47	52	99
Mean (Standard Deviation) Unit of Measure: units on a scale
	0.39 (4.04)	-3.39 (5.59)	-2.16 (3.61)	-2.74 (4.67)

10.Secondary Outcome


Title	Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 12
Description	The SPARCC scoring method for lesions found on the Magnetic Resonance ...
Description	The SPARCC scoring method for lesions found on the Magnetic Resonance Imaging (MRI) is based on an abnormal increased signal on the Short-Tau-Inversion Recovery (STIR) sequence, representing bone marrow edema. Total Sacroiliac (SI) joint SPARCC score can range from 0 to 72 with higher scores indicating higher joint inflammation. A negative value in SPARCC change from Baseline indicates an improvement from Baseline. The higher the negative value the higher the reduction of inflammation.
Time Frame	From Baseline to Week 12

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo (FAS)	CZP 200 mg Q2W (FAS)	CZP 400 mg Q4W (FAS)	CZP 200 mg Q2W and CZP 400 mg Q4W (FAS)
Arm/Group Description:	Matching Placebo to Certolizumab Pe...	Subjects received Certolizumab Pego...	Subjects received Certolizumab Pego...	This arm shows a combination of arm...
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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.	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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).	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. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).	This arm shows a combination of arm CZP 200 mg Q2W and arm CZP 400 mg 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)/ 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. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).
Overall Number of Participants Analyzed	45	45	50	95
Mean (Standard Deviation) Unit of Measure: units on a scale
	-1.33 (8.33)	-3.61 (6.94)	-4.98 (8.47)	-4.33 (7.77)

Adverse Events

Time Frame	Adverse Events (AEs) were collected from Baseline (Week 0) until study end (Week 204). AEs refer to the Safety Set including all randomized subjects who took at least 1 dose of CZP.
Adverse Event Reporting Description	As per study design, placebo arm subjects shifted either at Week 16 or 24 to CZP treatment. For the Placebo (PBO) group, CZP data from PBO subjects are not utilized. The All CZP 200 mg + 400 mg group shows CZP 200 mg, CZP 400 mg and the escaped PBO subjects with their CZP data.

Arm/Group Title	All CZP 200 mg (Safety Analysis)		All CZP 400 mg (Safety Analysis)		All CZP 200 mg + 400 mg		Placebo
Arm/Group Description	All subjects who received CZP at th...		All subjects who received CZP at th...		This arm shows all patients treated...		Matching Placebo to Certolizumab Pe...
Arm/Group Description	All subjects who received CZP at the specified dose (200 mg) at some point during the study, including subjects who were originally randomized to receive placebo and were switched to CZP at Week 16 or Week 24. Placebo : Matching Placebo to CZP injection. CZP 200 mg Q2W : 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).		All subjects who received CZP at the specified dose (400 mg) at some point during the study, including subjects who were originally randomized to receive placebo and were switched to CZP at Week 16 or Week 24. Placebo : Matching Placebo to CZP injection. CZP 400 mg Q4W : 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).		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 and arm All CZP 400 mg.		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 on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg every two weeks (Q2W) or CZP 400 mg every four weeks (Q4W). Placebo : Matching Placebo to CZP injection.
All-Cause Mortality
	All CZP 200 mg (Safety Analysis)		All CZP 400 mg (Safety Analysis)		All CZP 200 mg + 400 mg		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events Serious Adverse Events
	All CZP 200 mg (Safety Analysis)		All CZP 400 mg (Safety Analysis)		All CZP 200 mg + 400 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/158 (22.15%)		34/157 (21.66%)		69/315 (21.90%)		5/107 (4.67%)
Blood and lymphatic system disorders
Hilar lymphadenopathy ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Lymphadenopathy ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Paratracheal lymphadenopathy ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Cardiac disorders
Coronary artery disease ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Acute myocardial infarction ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Atrial fibrillation ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Supraventricular tachycardia ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Eye disorders
Retinal vein occlusion ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Gastrointestinal disorders
Colitis ^* 1	0/158 (0.00%)	0	3/157 (1.91%)	3	3/315 (0.95%)	3	0/107 (0.00%)	0
Colitis ulcerative ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Sigmoiditis ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Diarrhoea ^* 1	0/158 (0.00%)	0	2/157 (1.27%)	2	2/315 (0.63%)	2	0/107 (0.00%)	0
Gastritis ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Abdominal pain ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Crohn's disease ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Inguinal hernia ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Lower gastrointestinal haemorrhage ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Inflammatory bowel disease ^* 1	0/158 (0.00%)	0	0/157 (0.00%)	0	0/315 (0.00%)	0	1/107 (0.93%)	1
General disorders
Chest pain ^* 1	1/158 (0.63%)	1	1/157 (0.64%)	1	2/315 (0.63%)	2	0/107 (0.00%)	0
Non-cardiac chest pain ^* 1	2/158 (1.27%)	2	0/157 (0.00%)	0	2/315 (0.63%)	2	2/107 (1.87%)	2
Hepatobiliary disorders
Cholelithiasis ^* 1	0/158 (0.00%)	0	2/157 (1.27%)	2	2/315 (0.63%)	2	0/107 (0.00%)	0
Cholelithiasis migration ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Hepatitis ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Immune system disorders
Hypersensitivity ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	1/107 (0.93%)	1
Infections and infestations
Anal abscess ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Appendicitis ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Diverticulitis ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Mycobacterial infection ^* 1	1/158 (0.63%)	1	1/157 (0.64%)	1	2/315 (0.63%)	2	0/107 (0.00%)	0
Cellulitis ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Oesophageal candidiasis ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Haemophilus infection ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Herpes zoster disseminated ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Pneumonia legionella ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Pneumonia ^* 1	3/158 (1.90%)	5	0/157 (0.00%)	0	3/315 (0.95%)	5	0/107 (0.00%)	0
Infected dermal cyst ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Subcutaneous abscess ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Latent tuberculosis ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Pulmonary tuberculosis ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Acute sinusitis ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Laryngitis ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Upper respiratory tract infection ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Pyelonephritis ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Injury, poisoning and procedural complications
Joint dislocation ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Multiple fractures ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Meniscus lesion ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Ligament rupture ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Radius fracture ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Investigations
Gamma-glutamyltransferase increased ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Weight decreased ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Metabolism and nutrition disorders
Hypoglycaemia ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthritis ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Rotator cuff syndrome ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Back pain ^* 1	1/158 (0.63%)	1	1/157 (0.64%)	1	2/315 (0.63%)	2	0/107 (0.00%)	0
Osteoarthritis ^* 1	3/158 (1.90%)	3	0/157 (0.00%)	0	3/315 (0.95%)	3	0/107 (0.00%)	0
Ankylosing spondylitis ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Spondylitis ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholesterol granuloma ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Breast cancer ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Squamous cell carcinoma of the ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Astrocytoma ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Morton's neuroma ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Renal cell carcinoma ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Nervous system disorders
Intracranial aneurysm ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Cerebrovascular insufficiency ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Transient ischaemic attack ^* 1	2/158 (1.27%)	2	0/157 (0.00%)	0	2/315 (0.63%)	2	0/107 (0.00%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Pregnancy on contraceptive ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Psychiatric disorders
Major depression ^* 1	1/158 (0.63%)	2	1/157 (0.64%)	1	2/315 (0.63%)	3	0/107 (0.00%)	0
Hallucination ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Psychotic disorder ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Conversion disorder ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Renal and urinary disorders
Ureteric obstruction ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Renal colic ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Calculus ureteric ^* 1	0/158 (0.00%)	0	0/157 (0.00%)	0	0/315 (0.00%)	0	1/107 (0.93%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary ^* 1	1/158 (0.63%)	2	0/157 (0.00%)	0	1/315 (0.32%)	2	0/107 (0.00%)	0
Hypoxia ^* 1	1/158 (0.63%)	2	0/157 (0.00%)	0	1/315 (0.32%)	2	0/107 (0.00%)	0
Diffuse alveolar damage ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Nasal congestion ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Nasal polyps ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Skin and subcutaneous tissue disorders
Psoriasis ^* 1	0/158 (0.00%)	0	1/157 (0.64%)	1	1/315 (0.32%)	1	0/107 (0.00%)	0
Dermal cyst ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Surgical and medical procedures
Bone graft ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
Abortion induced ^* 1	1/158 (0.63%)	1	0/157 (0.00%)	0	1/315 (0.32%)	1	0/107 (0.00%)	0
* 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 (Safety Analysis)		All CZP 400 mg (Safety Analysis)		All CZP 200 mg + 400 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	142/158 (89.87%)		127/157 (80.89%)		269/315 (85.40%)		28/107 (26.17%)
Eye disorders
Uveitis ^* 1	11/158 (6.96%)	15	8/157 (5.10%)	12	19/315 (6.03%)	27	0/107 (0.00%)	0
Conjunctivitis ^* 1	5/158 (3.16%)	6	8/157 (5.10%)	9	13/315 (4.13%)	15	0/107 (0.00%)	0
Gastrointestinal disorders
Diarrhoea ^* 1	10/158 (6.33%)	13	20/157 (12.74%)	26	30/315 (9.52%)	39	0/107 (0.00%)	0
Gastritis ^* 1	8/158 (5.06%)	8	5/157 (3.18%)	5	13/315 (4.13%)	13	0/107 (0.00%)	0
Immune system disorders
Seasonal allergy ^* 1	7/158 (4.43%)	8	8/157 (5.10%)	11	15/315 (4.76%)	19	0/107 (0.00%)	0
Infections and infestations
Nasopharyngitis ^* 1	47/158 (29.75%)	80	43/157 (27.39%)	83	90/315 (28.57%)	163	7/107 (6.54%)	8
Upper respiratory tract infection ^* 1	35/158 (22.15%)	53	28/157 (17.83%)	58	63/315 (20.00%)	111	3/107 (2.80%)	3
Bronchitis ^* 1	24/158 (15.19%)	28	17/157 (10.83%)	18	41/315 (13.02%)	46	0/107 (0.00%)	0
Pharyngitis ^* 1	24/158 (15.19%)	36	11/157 (7.01%)	17	35/315 (11.11%)	53	0/107 (0.00%)	0
Sinusitis ^* 1	17/158 (10.76%)	21	8/157 (5.10%)	10	25/315 (7.94%)	31	0/107 (0.00%)	0
Urinary tract infection ^* 1	10/158 (6.33%)	17	11/157 (7.01%)	15	21/315 (6.67%)	32	4/107 (3.74%)	4
Rhinitis ^* 1	15/158 (9.49%)	22	6/157 (3.82%)	8	21/315 (6.67%)	30	0/107 (0.00%)	0
Influenza ^* 1	9/158 (5.70%)	10	11/157 (7.01%)	14	20/315 (6.35%)	24	0/107 (0.00%)	0
Tonsillitis ^* 1	8/158 (5.06%)	10	9/157 (5.73%)	11	17/315 (5.40%)	21	0/107 (0.00%)	0
Oral herpes ^* 1	9/158 (5.70%)	23	6/157 (3.82%)	7	15/315 (4.76%)	30	0/107 (0.00%)	0
Cystitis ^* 1	8/158 (5.06%)	13	6/157 (3.82%)	10	14/315 (4.44%)	21	0/107 (0.00%)	0
Gastroenteritis ^* 1	5/158 (3.16%)	5	9/157 (5.73%)	9	14/315 (4.44%)	14	0/107 (0.00%)	0
Viral infection ^* 1	9/158 (5.70%)	10	4/157 (2.55%)	4	13/315 (4.13%)	14	0/107 (0.00%)	0
Injury, poisoning and procedural complications
Contusion ^* 1	10/158 (6.33%)	18	9/157 (5.73%)	11	19/315 (6.03%)	29	0/107 (0.00%)	0
Investigations
Blood creatine phosphokinase increased ^* 1	14/158 (8.86%)	16	17/157 (10.83%)	23	31/315 (9.84%)	39	2/107 (1.87%)	3
Alanine aminotransferase increased ^* 1	11/158 (6.96%)	14	8/157 (5.10%)	10	19/315 (6.03%)	24	0/107 (0.00%)	0
Tuberculin test positive ^* 1	8/158 (5.06%)	8	7/157 (4.46%)	7	15/315 (4.76%)	15	0/107 (0.00%)	0
Aspartate aminotransferase increased ^* 1	6/158 (3.80%)	6	8/157 (5.10%)	9	14/315 (4.44%)	15	0/107 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	22/158 (13.92%)	42	11/157 (7.01%)	20	33/315 (10.48%)	62	0/107 (0.00%)	0
Back pain ^* 1	14/158 (8.86%)	18	11/157 (7.01%)	19	25/315 (7.94%)	37	0/107 (0.00%)	0
Spondylitis ^* 1	12/158 (7.59%)	22	13/157 (8.28%)	14	25/315 (7.94%)	36	0/107 (0.00%)	0
Ankylosing spondylitis ^* 1	11/158 (6.96%)	17	5/157 (3.18%)	8	16/315 (5.08%)	25	0/107 (0.00%)	0
Pain in extremity ^* 1	10/158 (6.33%)	11	3/157 (1.91%)	4	13/315 (4.13%)	15	0/107 (0.00%)	0
Nervous system disorders
Headache ^* 1	17/158 (10.76%)	25	18/157 (11.46%)	31	35/315 (11.11%)	56	7/107 (6.54%)	11
Psychiatric disorders
Depression ^* 1	9/158 (5.70%)	10	4/157 (2.55%)	5	13/315 (4.13%)	15	0/107 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough ^* 1	13/158 (8.23%)	16	11/157 (7.01%)	13	24/315 (7.62%)	29	0/107 (0.00%)	0
Oropharyngeal pain ^* 1	12/158 (7.59%)	15	6/157 (3.82%)	6	18/315 (5.71%)	21	0/107 (0.00%)	0
Skin and subcutaneous tissue disorders
Rash ^* 1	11/158 (6.96%)	15	14/157 (8.92%)	18	25/315 (7.94%)	33	2/107 (1.87%)	2
Psoriasis ^* 1	8/158 (5.06%)	14	6/157 (3.82%)	9	14/315 (4.44%)	23	0/107 (0.00%)	0
Eczema ^* 1	4/158 (2.53%)	6	8/157 (5.10%)	13	12/315 (3.81%)	19	0/107 (0.00%)	0
Vascular disorders
Hypertension ^* 1	20/158 (12.66%)	26	11/157 (7.01%)	11	31/315 (9.84%)	37	4/107 (3.74%)	4
* 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

Layout table for Results Point of Contact information

Name/Title:	UCB
Organization:	Cares
Phone:	+1887822 ext 9493

Publications of Results:

Landewe R, Braun J, Deodhar A, Dougados M, Maksymowych WP, Mease PJ, Reveille JD, Rudwaleit M, van der Heijde D, Stach C, Hoepken B, Fichtner A, Coteur G, de Longueville M, Sieper J. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study. Ann Rheum Dis. 2014 Jan;73(1):39-47. doi: 10.1136/annrheumdis-2013-204231. Epub 2013 Sep 6.

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

Baraliakos X, Kruse S, Auteri SE, de Peyrecave N, Nurminen T, Kumke T, Hoepken B, Braun J. Certolizumab pegol treatment in axial spondyloarthritis mitigates fat lesion development: 4-year post-hoc MRI results from a phase 3 study. Rheumatology (Oxford). 2022 Jul 6;61(7):2875-2885. doi: 10.1093/rheumatology/keab841.

Landewe R, Nurminen T, Davies O, Baeten D. A single determination of C-reactive protein does not suffice to declare a patient with a diagnosis of axial spondyloarthritis 'CRP-negative'. Arthritis Res Ther. 2018 Sep 14;20(1):209. doi: 10.1186/s13075-018-1707-8.

van der Heijde D, Braun J, Rudwaleit M, Purcaru O, Kavanaugh AF. Improvements in workplace and household productivity with certolizumab pegol treatment in axial spondyloarthritis: results to week 96 of a phase III study. RMD Open. 2018 Apr 9;4(1):e000659. doi: 10.1136/rmdopen-2018-000659. eCollection 2018.

van der Heijde D, Dougados M, Landewe R, Sieper J, Maksymowych WP, Rudwaleit M, Van den Bosch F, Braun J, Mease PJ, Kivitz AJ, Walsh J, Davies O, Bauer L, Hoepken B, Peterson L, Deodhar A. Sustained efficacy, safety and patient-reported outcomes of certolizumab pegol in axial spondyloarthritis: 4-year outcomes from RAPID-axSpA. Rheumatology (Oxford). 2017 Sep 1;56(9):1498-1509. doi: 10.1093/rheumatology/kex174.

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.

Rudwaleit M, Rosenbaum JT, Landewe R, Marzo-Ortega H, Sieper J, van der Heijde D, Davies O, Bartz H, Hoepken B, Nurminen T, Deodhar A. Observed Incidence of Uveitis Following Certolizumab Pegol Treatment in Patients With Axial Spondyloarthritis. Arthritis Care Res (Hoboken). 2016 Jun;68(6):838-44. doi: 10.1002/acr.22848.

Sieper J, Kivitz A, van Tubergen A, Deodhar A, Coteur G, Woltering F, Landewe R. Impact of Certolizumab Pegol on Patient-Reported Outcomes in Patients With Axial Spondyloarthritis. Arthritis Care Res (Hoboken). 2015 Oct;67(10):1475-80. doi: 10.1002/acr.22594.

Layout table for additonal information

Responsible Party:	UCB Pharma ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier:	NCT01087762
Other Study ID Numbers:	AS001 2009-011719-19 ( EudraCT Number )
First Submitted:	March 15, 2010
First Posted:	March 16, 2010
Results First Submitted:	November 6, 2013
Results First Posted:	December 25, 2013
Last Update Posted:	August 1, 2018

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