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

• Sponsor: UCB BIOSCIENCES GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01087788
• Collaborator: (none)
• Enrollment: 409
• Locations: 92
• Arms: 7
• Duration (Months): 65
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of Certolizumab Pegol (CZP) in subjects with adult onset active and progressive Psoriatic Arthritis (PsA).

Condition or Disease	Intervention/Treatment	Phase
Arthritis, Psoriatic	Biological: CZP 200 mg Q2W; Biological: CZP 400 mg Q4W; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 409 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase 3, Multicenter, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Subjects With Adult-Onset Active and Progressive Psoriatic Arthritis (PsA)
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CZP 200 mg Q2W 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.	Biological: CZP 200 mg Q2W; 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).; Other Names: Cimzia Certolizumab Pegol ; Other: Placebo; Matching Placebo to CZP injection.
Experimental: CZP 400 mg Q4W 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.	Biological: CZP 400 mg Q4W; 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).; Other Names: Cimzia Certolizumab Pegol ; Other: Placebo; Matching Placebo to CZP injection.
Placebo Comparator: Placebo 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).	Other: Placebo; Matching Placebo to CZP injection.
Other: Placebo to CZP 200 mg escape on Week 16 Matching Placebo to CZP injections from Week 0 to Week 16. Subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16 and were treated with three loading doses of CZP 400 mg sc on Weeks 16, 18 and 20, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 22 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.	Biological: CZP 200 mg Q2W; 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).; Other Names: Cimzia Certolizumab Pegol ; Other: Placebo; Matching Placebo to CZP injection.
Other: Placebo to CZP 400 mg escape on Week 16 Matching Placebo to CZP injections from Week 0 to Week 16. Subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16 and were treated with three loading doses of CZP 400 mg sc on Weeks 16, 18 and 20, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 24 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.	Biological: CZP 400 mg Q4W; 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).; Other Names: Cimzia Certolizumab Pegol ; Other: Placebo; Matching Placebo to CZP injection.
Other: Placebo to CZP 200 mg on Week 24 Matching Placebo to CZP injections from Week 0 to Week 24. Three loading doses of CZP 400 mg sc were given on Weeks 24, 26 and 28, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 30 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.	Biological: CZP 200 mg Q2W; 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).; Other Names: Cimzia Certolizumab Pegol ; Other: Placebo; Matching Placebo to CZP injection.
Other: Placebo to CZP 400 mg on Week 24 Matching Placebo to CZP injections from Week 0 to Week 24. Three loading doses of CZP 400 mg sc were given on Weeks 24, 26 and 28, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 32 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.	Biological: CZP 400 mg Q4W; 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).; Other Names: Cimzia Certolizumab Pegol ; Other: Placebo; Matching Placebo to CZP injection.

Outcome Measures

Primary Outcome Measures

1. American College of Rheumatology 20 (ACR20) Response at Week 12 [Week 12]

   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).

2. Change From Baseline in Modified Total Sharp Score (mTSS) in Modification for Psoriatic Arthritis at Week 24 [From Baseline to Week 24]

   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.

Secondary Outcome Measures

1. American College of Rheumatology 20 (ACR20) Response at Week 24 [Week 24]

   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).

2. Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24 [From Baseline to Week 24]

   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.

3. 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 [Week 24]

   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.

4. Change From Baseline in Modified Total Sharp Score (mTSS) at Week 48 [From Baseline to Week 48]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of adult-onset Psoriatic Arthritis (PsA) of at least 6 months' duration as defined by the Classification Criteria for Psoriatic Arthritis (CASPAR criteria)

• Active Psoriatic Skin Lesions or a documented history of Psoriasis

• Active Arthritis with ≥ 3 tender joints at Screening and Baseline, ≥ 3 swollen joints at Screening and Baseline and fulfilling at least 1 of the following 2 criteria during the Screening Period:

1. Erythrocyte Sedimentation Rate (ESR) (Westergren) ≥ 28 mm/hour

2. C-reactive protein (CRP) > Upper Limit Normal (ULN)

• Failure to 1 or more treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

Exclusion Criteria:

• Diagnosis of any other inflammatory Arthritis or known diagnosis of Fibromyalgia

• Exposure to more than 1 Tumor Necrosis Factor α (TNFα) antagonist or to more than 2 previous biological response modifiers for PsA or Psoriasis

• Any non-biological systemic treatment of Psoriasis; phototherapy; topical agents

• History of chronic or recurrent infections

• High risk of infection

• Live vaccination within the 8 weeks prior to Baseline

• Concurrent malignancy or a history of malignancy

• Class III or IV congestive Heart Failure - New York Heart Association (NYHA)

• Demyelinating disease of the central nervous system

• Clinically significant laboratory abnormalities

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	961	Birmingham	Alabama	United States
2	953	Tuscaloosa	Alabama	United States
3	954	Peoria	Arizona	United States
4	971	Scottsdale	Arizona	United States
5	966	Palm Desert	California	United States
6	952	San Diego	California	United States
7	957	Aventura	Florida	United States
8	962	Fort Lauderdale	Florida	United States
9	959	Orange Park	Florida	United States
10	958	Vero Beach	Florida	United States
11	964	Hagerstown	Maryland	United States
12	960	Kalamazoo	Michigan	United States
13	969	Eagan	Minnesota	United States
14	984	Flowood	Mississippi	United States
15	965	Florissant	Missouri	United States
16	950	Saint Louis	Missouri	United States
17	985	Brooklyn	New York	United States
18	963	Asheville	North Carolina	United States
19	976	Cleveland	Ohio	United States
20	951	Middleburg Heights	Ohio	United States
21	970	Oklahoma City	Oklahoma	United States
22	982	Portland	Oregon	United States
23	972	Duncansville	Pennsylvania	United States
24	975	Dallas	Texas	United States
25	978	Houston	Texas	United States
26	967	San Antonio	Texas	United States
27	968	Seattle	Washington	United States
28	700	Buenos Aires		Argentina
29	704	Buenos Aires		Argentina
30	707	Ciudad Autonoma de Buenos Aires		Argentina
31	705	Cordoba		Argentina
32	706	Rosario		Argentina
33	710	San Juan		Argentina
34	702	San Miguel De Tucuman		Argentina
35	708	San Miguel de Tucuman		Argentina
36	152	Gent		Belgium
37	151	Liege		Belgium
38	750	Curitiba		Brazil
39	757	Goias		Brazil
40	761	Goiâna		Brazil
41	753	Porto Alegre		Brazil
42	907	Victoria	British Columbia	Canada
43	900	St. John's	Newfoundland and Labrador	Canada
44	904	Toronto	Ontario	Canada
45	910	Windsor	Ontario	Canada
46	905	Trois-Rivires	Quebec	Canada
47	504	Brno		Czechia
48	501	Hlucin		Czechia
49	500	Pardubice		Czechia
50	502	Praha 2		Czechia
51	505	Terezin		Czechia
52	503	Zlin		Czechia
53	206	Montpellier		France
54	204	Paris		France
55	202	Tours		France
56	252	Bad Nauheim		Germany
57	257	Berlin		Germany
58	258	Berlin		Germany
59	262	Frankfurt		Germany
60	255	Freiburg		Germany
61	254	Hamburg		Germany
62	253	Leipzig		Germany
63	263	München		Germany
64	256	Ratingen		Germany
65	303	Budapest		Hungary
66	304	Budapest		Hungary
67	302	Debrecen		Hungary
68	301	Gyula		Hungary
69	306	Miskolc		Hungary
70	300	Veszprém		Hungary
71	100	Dublin 4		Ireland
72	352	Ancona		Italy
73	350	Pisa		Italy
74	802	Cuernavaca		Mexico
75	803	Mexico D.F.		Mexico
76	458	Bialystok		Poland
77	452	Dabrowka		Poland
78	455	Elblag		Poland
79	459	Gdansk		Poland
80	457	Krakow		Poland
81	450	Lublin		Poland
82	454	Poznan		Poland
83	453	Torun		Poland
84	456	Warszawa		Poland
85	462	Warszawa		Poland
86	555	Madrid		Spain
87	550	Mérida		Spain
88	552	Santiago de Compostela		Spain
89	553	Sevilla		Spain
90	605	Barnsley		United Kingdom
91	602	London		United Kingdom
92	601	Salford		United Kingdom

Sponsors and Collaborators

• UCB BIOSCIENCES GmbH

Investigators

• Study Director: UCB Clinical Trial Call Center, [phone] UCB

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Product Information
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: UCB BIOSCIENCES GmbH
• ClinicalTrials.gov Identifier: NCT01087788
• Other Study ID Numbers: PsA001; 2009-011720-59
• First Posted: Mar 16, 2010
• Last Update Posted: Aug 1, 2018
• Last Verified: Jan 1, 2017

• Keywords provided by UCB BIOSCIENCES GmbH: Certolizumab Pegol; Cimzia
• Additional relevant MeSH terms: Arthritis; Arthritis, Psoriatic; Certolizumab Pegol

Study Results

Participant Flow

Recruitment Details	This study started to enroll patients in March 2010 and concluded in August 2015.
Pre-assignment Detail	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	0	0
Received CZP 400 mg Q4W at 16 Weeks	29	0	0
COMPLETED	120	128	120
NOT COMPLETED	16	10	15
Period Title: 24-weeks Double-blind Period
STARTED	120	128	120
Received CZP 200 mg Q2W at 24 Weeks	60	0	0
Received CZP 400 mg Q2W at 24 Weeks	60	0	0
COMPLETED	113	123	114
NOT COMPLETED	7	5	6
Period Title: 24-weeks Double-blind Period
STARTED	111	121	114
COMPLETED	81	97	86
NOT COMPLETED	30	24	28

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.
Overall Participants	136	138	135	409
Age (Count of Participants)
<=18 years	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 (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (11.1)	48.2 (12.3)	47.1 (10.8)	47.6 (11.4)
Sex: Female, Male (Count of 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.
Measure Participants	136	138	135
Number (95% Confidence Interval) [percentage of participants]	24.3 17.9%	58.0 42%	51.9 38.4%

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
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
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	33.7
	Confidence Interval	(2-Sided) 95%; 22.8 to 44.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	27.6
	Confidence Interval	(2-Sided) 95%; 16.5 to 38.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.
Measure Participants	136	138	135	273
Pre-defined results	28.92	11.52	25.05	18.28
Re-analysis results ( n = 123, 130, 123, 253)	0.18	-0.02	0.09	0.03

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
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
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

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
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
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

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
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
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

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.
Measure Participants	136	138	135
Number (95% Confidence Interval) [percentage of participants]	23.5 17.3%	63.8 46.2%	56.3 41.7%

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
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
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	40.2
	Confidence Interval	(2-Sided) 95%; 29.5 to 51.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
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
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	32.8
	Confidence Interval	(2-Sided) 95%; 21.8 to 43.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.
Measure Participants	136	138	135	273
Least Squares Mean (95% Confidence Interval) [units on a scale]	-0.19	-0.54	-0.46	-0.50

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
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
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

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.
Measure Participants	86	90	76	166
Number (95% Confidence Interval) [percentage of participants]	15.1 11.1%	62.2 45.1%	60.5 44.8%	61.4 15%

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
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
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	46.3
	Confidence Interval	(2-Sided) 95%; 35.7 to 56.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.
Measure Participants	136	138	135	273
Predefined results: Overall	0.32	0.15	0.11	0.13
Post-hoc results: Basel. mTSS > 6 (n=61,65,65,130)	0.78	0.31	0.22	0.26

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
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
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

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
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
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

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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
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 (24.7%)		51/195 (26.2%)		100/393 (25.4%)
Blood and lymphatic system disorders
Splenomegaly	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Thrombocytopenia	0/198 (0%)	0	1/195 (0.5%)	2	1/393 (0.3%)	2
Cardiac disorders
Coronary artery thrombosis	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Angina unstable	1/198 (0.5%)	1	1/195 (0.5%)	1	2/393 (0.5%)	2
Myocardial infarction	2/198 (1%)	2	0/195 (0%)	0	2/393 (0.5%)	2
Acute myocardial infarction	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Myocarditis	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Atrial fibrillation	1/198 (0.5%)	1	1/195 (0.5%)	1	2/393 (0.5%)	2
Cardiac arrest	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Ear and labyrinth disorders
Tinnitus	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Eye disorders
Cataract	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Diplopia	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Gastrointestinal disorders
Abdominal hernia	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Pancreatitis acute	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Abdominal pain	1/198 (0.5%)	2	0/195 (0%)	0	1/393 (0.3%)	2
Crohn's disease	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Hypoaesthesia oral	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
General disorders
Sudden death	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Pyrexia	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Chest pain	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Hepatobiliary disorders
Biliary colic	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Cholelithiasis	1/198 (0.5%)	1	2/195 (1%)	2	3/393 (0.8%)	3
Cholecystitis	0/198 (0%)	0	2/195 (1%)	2	2/393 (0.5%)	2
Biliary dyskinesia	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Bile duct obstruction	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Infections and infestations
Diverticulitis	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Cellulitis	2/198 (1%)	2	0/195 (0%)	0	2/393 (0.5%)	2
Arthritis bacterial	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Herpes zoster	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Device related infection	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Postoperative wound infection	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Pneumonia	1/198 (0.5%)	1	3/195 (1.5%)	4	4/393 (1%)	5
Bronchitis	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Bronchopneumonia	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
HIV infection	1/198 (0.5%)	1	1/195 (0.5%)	1	2/393 (0.5%)	2
Sepsis	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Staphylococcal abscess	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Erysipelas	2/198 (1%)	2	0/195 (0%)	0	2/393 (0.5%)	2
Pyoderma streptococcal	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Latent tuberculosis	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Upper respiratory tract infection	1/198 (0.5%)	1	1/195 (0.5%)	1	2/393 (0.5%)	2
Chronic tonsillitis	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Urinary tract infection	1/198 (0.5%)	1	2/195 (1%)	2	3/393 (0.8%)	3
Pyelonephritis	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Pyelonephritis acute	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Injury, poisoning and procedural complications
Concussion	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Joint injury	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Synovial rupture	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Foot fracture	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Lower limb fracture	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Tendon rupture	0/198 (0%)	0	2/195 (1%)	2	2/393 (0.5%)	2
Animal bite	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Wound	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Anastomotic complication	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Hand fracture	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Investigations
Hepatic enzyme increased	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Metabolism and nutrition disorders
Diabetes mellitus	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Obesity	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Hyperglycaemia	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Dehydration	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Musculoskeletal and connective tissue disorders
Arthritis	2/198 (1%)	2	1/195 (0.5%)	1	3/393 (0.8%)	3
Foot deformity	0/198 (0%)	0	2/195 (1%)	2	2/393 (0.5%)	2
Lupus-like syndrome	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Osteoarthritis	1/198 (0.5%)	1	3/195 (1.5%)	3	4/393 (1%)	4
Psoriatic arthropathy	5/198 (2.5%)	5	3/195 (1.5%)	7	8/393 (2%)	12
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/198 (0.5%)	1	2/195 (1%)	2	3/393 (0.8%)	3
Gastrointestinal cancer metastatic	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Lymphoma	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Ovarian cancer	1/198 (0.5%)	2	0/195 (0%)	0	1/393 (0.3%)	2
Benign neoplasm of thyroid gland	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Nervous system disorders
Cerebrovascular accident	1/198 (0.5%)	1	1/195 (0.5%)	1	2/393 (0.5%)	2
Dysgraphia	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Syncope	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Formication	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Paralysis	1/198 (0.5%)	2	0/195 (0%)	0	1/393 (0.3%)	2
Epilepsy	0/198 (0%)	0	1/195 (0.5%)	2	1/393 (0.3%)	2
Hypoaesthesia	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Speech disorder	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Transient ischaemic attack	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Pregnancy, puerperium and perinatal conditions
Pregnancy	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Pregnancy on contraceptive	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Psychiatric disorders
Bipolar I disorder	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Acute stress disorder	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Post-traumatic stress disorder	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Renal and urinary disorders
Urinary incontinence	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Renal cyst	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Calculus ureteric	0/198 (0%)	0	2/195 (1%)	2	2/393 (0.5%)	2
Renal colic	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Reproductive system and breast disorders
Metrorrhagia	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Genital prolapse	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Uterine haemorrhage	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Uterine polyp	0/198 (0%)	0	2/195 (1%)	2	2/393 (0.5%)	2
Vulvar dysplasia	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Haemoptysis	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Lung infiltration	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Pleurisy	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Pulmonary embolism	3/198 (1.5%)	3	0/195 (0%)	0	3/393 (0.8%)	3
Skin and subcutaneous tissue disorders
Cutaneous lupus erythematosus	1/198 (0.5%)	2	0/195 (0%)	0	1/393 (0.3%)	2
Skin ulcer	3/198 (1.5%)	4	1/195 (0.5%)	1	4/393 (1%)	5
Social circumstances
Pregnancy of partner	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Surgical and medical procedures
Hip arthroplasty	0/198 (0%)	0	1/195 (0.5%)	1	1/393 (0.3%)	1
Vascular disorders
Haematoma	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Thrombophlebitis	1/198 (0.5%)	1	1/195 (0.5%)	1	2/393 (0.5%)	2
Deep vein thrombosis	1/198 (0.5%)	1	0/195 (0%)	0	1/393 (0.3%)	1
Other (Not Including 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	158/198 (79.8%)		153/195 (78.5%)		311/393 (79.1%)
Gastrointestinal disorders
Diarrhoea	15/198 (7.6%)	20	11/195 (5.6%)	15	26/393 (6.6%)	35
Abdominal pain	12/198 (6.1%)	13	9/195 (4.6%)	10	21/393 (5.3%)	23
Abdominal pain upper	14/198 (7.1%)	16	5/195 (2.6%)	9	19/393 (4.8%)	25
Nausea	10/198 (5.1%)	11	8/195 (4.1%)	9	18/393 (4.6%)	20
Infections and infestations
Upper respiratory tract infection	44/198 (22.2%)	81	49/195 (25.1%)	73	93/393 (23.7%)	154
Nasopharyngitis	45/198 (22.7%)	87	42/195 (21.5%)	91	87/393 (22.1%)	178
Pharyngitis	24/198 (12.1%)	44	27/195 (13.8%)	37	51/393 (13%)	81
Bronchitis	28/198 (14.1%)	36	22/195 (11.3%)	29	50/393 (12.7%)	65
Urinary tract infection	13/198 (6.6%)	18	26/195 (13.3%)	35	39/393 (9.9%)	53
Sinusitis	19/198 (9.6%)	32	13/195 (6.7%)	33	32/393 (8.1%)	65
Gastroenteritis	14/198 (7.1%)	18	8/195 (4.1%)	8	22/393 (5.6%)	26
Oral herpes	10/198 (5.1%)	25	11/195 (5.6%)	18	21/393 (5.3%)	43
Influenza	13/198 (6.6%)	15	8/195 (4.1%)	9	21/393 (5.3%)	24
Tonsillitis	11/198 (5.6%)	11	8/195 (4.1%)	12	19/393 (4.8%)	23
Rhinitis	10/198 (5.1%)	11	9/195 (4.6%)	9	19/393 (4.8%)	20
Latent tuberculosis	6/198 (3%)	6	12/195 (6.2%)	12	18/393 (4.6%)	18
Viral infection	9/198 (4.5%)	12	7/195 (3.6%)	7	16/393 (4.1%)	19
Injury, poisoning and procedural complications
Contusion	15/198 (7.6%)	21	9/195 (4.6%)	10	24/393 (6.1%)	31
Investigations
Alanine aminotransferase increased	17/198 (8.6%)	23	15/195 (7.7%)	25	32/393 (8.1%)	48
Blood creatine phosphokinase increased	15/198 (7.6%)	28	13/195 (6.7%)	25	28/393 (7.1%)	53
Aspartate aminotransferase increased	9/198 (4.5%)	13	11/195 (5.6%)	17	20/393 (5.1%)	30
Gamma-glutamyltransferase increased	8/198 (4%)	11	12/195 (6.2%)	15	20/393 (5.1%)	26
Musculoskeletal and connective tissue disorders
Back pain	24/198 (12.1%)	28	22/195 (11.3%)	26	46/393 (11.7%)	54
Psoriatic arthropathy	24/198 (12.1%)	41	15/195 (7.7%)	23	39/393 (9.9%)	64
Arthralgia	20/198 (10.1%)	28	18/195 (9.2%)	28	38/393 (9.7%)	56
Nervous system disorders
Headache	18/198 (9.1%)	19	17/195 (8.7%)	20	35/393 (8.9%)	39
Dizziness	5/198 (2.5%)	5	10/195 (5.1%)	10	15/393 (3.8%)	15
Psychiatric disorders
Depression	11/198 (5.6%)	12	9/195 (4.6%)	12	20/393 (5.1%)	24
Respiratory, thoracic and mediastinal disorders
Cough	8/198 (4%)	9	14/195 (7.2%)	14	22/393 (5.6%)	23
Oropharyngeal pain	6/198 (3%)	6	10/195 (5.1%)	13	16/393 (4.1%)	19
Skin and subcutaneous tissue disorders
Psoriasis	22/198 (11.1%)	31	19/195 (9.7%)	21	41/393 (10.4%)	52
Rash	10/198 (5.1%)	16	9/195 (4.6%)	9	19/393 (4.8%)	25
Vascular disorders
Hypertension	30/198 (15.2%)	33	16/195 (8.2%)	20	46/393 (11.7%)	53

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.