Trial Outcomes & Findings for Certolizumab Pegol in Subjects With Adult Onset Active and Progressive Psoriatic Arthritis (NCT NCT01087788)

Last Updated: 2018-08-01

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

409 participants

Primary outcome timeframe

Week 12

Results posted on

2018-08-01

Participant Flow

This study started to enroll patients in March 2010 and concluded in August 2015.

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.

Participant milestones

Participant milestones
Measure	Placebo 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).	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.	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.
24-weeks Double-blind Period STARTED	136	138	135
24-weeks Double-blind Period Received CZP 200 mg Q2W at 16 Weeks	30	0	0
24-weeks Double-blind Period Received CZP 400 mg Q4W at 16 Weeks	29	0	0
24-weeks Double-blind Period COMPLETED	120	128	120
24-weeks Double-blind Period NOT COMPLETED	16	10	15
24-weeks Dose-blind Period STARTED	120	128	120
24-weeks Dose-blind Period Received CZP 200 mg Q2W at 24 Weeks	60	0	0
24-weeks Dose-blind Period Received CZP 400 mg Q2W at 24 Weeks	60	0	0
24-weeks Dose-blind Period COMPLETED	113	123	114
24-weeks Dose-blind Period NOT COMPLETED	7	5	6
Open-Label Period (OL-P) STARTED	111	121	114
Open-Label Period (OL-P) COMPLETED	81	97	86
Open-Label Period (OL-P) NOT COMPLETED	30	24	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 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).	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.	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.
24-weeks Double-blind Period Lack of Efficacy	2	0	1
24-weeks Double-blind Period Protocol Violation	0	1	0
24-weeks Double-blind Period Lost to Follow-up	4	1	1
24-weeks Double-blind Period Withdrawal by Subject	7	2	5
24-weeks Double-blind Period AE, serious fatal	0	1	1
24-weeks Double-blind Period AE, serious non-fatal	0	2	3
24-weeks Double-blind Period AE, non-serious non-fatal	2	1	2
24-weeks Double-blind Period AE, unknown type	0	0	1
24-weeks Double-blind Period Patient (P) does not want to attend	1	0	0
24-weeks Double-blind Period Protocol violation (decision of monitor)	0	1	0
24-weeks Double-blind Period Exclusion criteria were not met	0	1	0
24-weeks Double-blind Period P cannot comply with scheduled visits	0	0	1
24-weeks Dose-blind Period Lack of Efficacy	0	2	1
24-weeks Dose-blind Period Lost to Follow-up	1	0	1
24-weeks Dose-blind Period Withdrawal by Subject	1	0	0
24-weeks Dose-blind Period AE, serious fatal	0	1	0
24-weeks Dose-blind Period AE, serious non-fatal	2	1	2
24-weeks Dose-blind Period AE, non-serious non-fatal	2	1	1
24-weeks Dose-blind Period Sponsor decision following missed visits	1	0	0
24-weeks Dose-blind Period Patient moved	0	0	1
Open-Label Period (OL-P) Lack of Efficacy	4	2	3
Open-Label Period (OL-P) Protocol Violation	2	1	0
Open-Label Period (OL-P) Lost to Follow-up	0	4	2
Open-Label Period (OL-P) Withdrawal by Subject	13	8	10
Open-Label Period (OL-P) AE, serious fatal	2	0	1
Open-Label Period (OL-P) AE, serious non-fatal	1	3	4
Open-Label Period (OL-P) AE, non-serious non-fatal	6	4	4
Open-Label Period (OL-P) SAE, non-fatal+AE, non-serious non-fatal	0	1	0
Open-Label Period (OL-P) AE, non-serious unknown	1	0	0
Open-Label Period (OL-P) Sponsor request	1	0	0
Open-Label Period (OL-P) Principal investigator decision	0	1	2
Open-Label Period (OL-P) No participation in study extension	0	0	1
Open-Label Period (OL-P) Personal reasons	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=136 Participants 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).	CZP 200 mg Q2W n=138 Participants 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.	CZP 400 mg Q4W n=135 Participants 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.	Total Title n=409 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	129 Participants n=5 Participants	126 Participants n=7 Participants	128 Participants n=5 Participants	383 Participants n=4 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	12 Participants n=7 Participants	7 Participants n=5 Participants	26 Participants n=4 Participants
Age, Continuous	47.3 years STANDARD_DEVIATION 11.1 • n=5 Participants	48.2 years STANDARD_DEVIATION 12.3 • n=7 Participants	47.1 years STANDARD_DEVIATION 10.8 • n=5 Participants	47.6 years STANDARD_DEVIATION 11.4 • n=4 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	74 Participants n=7 Participants	73 Participants n=5 Participants	226 Participants n=4 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	64 Participants n=7 Participants	62 Participants n=5 Participants	183 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 12

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized Set) n=136 Participants 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).	CZP 200 mg Q2W (Randomized Set) n=138 Participants 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.	CZP 400 mg Q4W (Randomized Set) n=135 Participants 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.	CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set) 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.
American College of Rheumatology 20 (ACR20) Response at Week 12	24.3 percentage of participants Interval 17.1 to 31.5	58.0 percentage of participants Interval 49.7 to 66.2	51.9 percentage of participants Interval 43.4 to 60.3	—

PRIMARY outcome

Timeframe: From Baseline to Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized Set) n=136 Participants 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).	CZP 200 mg Q2W (Randomized Set) n=138 Participants 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.	CZP 400 mg Q4W (Randomized Set) n=135 Participants 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.	CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set) n=273 Participants 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.
Change From Baseline in Modified Total Sharp Score (mTSS) in Modification for Psoriatic Arthritis at Week 24 Pre-defined results	28.92 units on a scale Interval 13.73 to 44.11	11.52 units on a scale Interval -3.4 to 26.45	25.05 units on a scale Interval 9.48 to 40.61	18.28 units on a scale Interval 6.34 to 30.23
Change From Baseline in Modified Total Sharp Score (mTSS) in Modification for Psoriatic Arthritis at Week 24 Re-analysis results ( n = 123, 130, 123, 253)	0.18 units on a scale Interval 0.04 to 0.33	-0.02 units on a scale Interval -0.16 to 0.11	0.09 units on a scale Interval -0.05 to 0.23	0.03 units on a scale Interval -0.08 to 0.14

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo (Randomized Set) n=136 Participants 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).	CZP 200 mg Q2W (Randomized Set) n=138 Participants 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.	CZP 400 mg Q4W (Randomized Set) n=135 Participants 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.	CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set) 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.
American College of Rheumatology 20 (ACR20) Response at Week 24	23.5 percentage of participants Interval 16.4 to 30.7	63.8 percentage of participants Interval 55.7 to 71.8	56.3 percentage of participants Interval 47.9 to 64.7	—

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized Set) n=136 Participants 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).	CZP 200 mg Q2W (Randomized Set) n=138 Participants 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.	CZP 400 mg Q4W (Randomized Set) n=135 Participants 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.	CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set) n=273 Participants 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.
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24	-0.19 units on a scale Interval -0.29 to -0.09	-0.54 units on a scale Interval -0.64 to -0.44	-0.46 units on a scale Interval -0.56 to -0.36	-0.50 units on a scale Interval -0.58 to -0.42

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized Set) n=86 Participants 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).	CZP 200 mg Q2W (Randomized Set) n=90 Participants 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.	CZP 400 mg Q4W (Randomized Set) n=76 Participants 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.	CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set) n=166 Participants 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.
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	15.1 percentage of participants Interval 7.5 to 22.7	62.2 percentage of participants Interval 52.2 to 72.2	60.5 percentage of participants Interval 49.5 to 71.5	61.4 percentage of participants Interval 54.0 to 68.8

SECONDARY outcome

Timeframe: From Baseline to Week 48

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized Set) n=136 Participants 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).	CZP 200 mg Q2W (Randomized Set) n=138 Participants 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.	CZP 400 mg Q4W (Randomized Set) n=135 Participants 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.	CZP 200 mg Q2W and CZP 400 mg Q4W (Randomized Set) n=273 Participants 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.
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 48 Predefined results: Overall	0.32 units on a scale Interval 0.1 to 0.55	0.15 units on a scale Interval -0.07 to 0.37	0.11 units on a scale Interval -0.12 to 0.34	0.13 units on a scale Interval -0.05 to 0.31
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 48 Post-hoc results: Basel. mTSS > 6 (n=61,65,65,130)	0.78 units on a scale Interval 0.31 to 1.25	0.31 units on a scale Interval -0.15 to 0.77	0.22 units on a scale Interval -0.24 to 0.67	0.26 units on a scale Interval -0.09 to 0.62

Adverse Events

All CZP 200 mg Q2W

Serious events: 49 serious events

Other events: 158 other events

Deaths: 0 deaths

All CZP 400 mg Q4W

Serious events: 51 serious events

Other events: 153 other events

Deaths: 0 deaths

All CZP 200 mg + 400 mg

Serious events: 100 serious events

Other events: 311 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

UCB

Cares

Phone: +1877 822

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Serious adverse events
Measure	All CZP 200 mg Q2W n=198 participants at risk 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.	All CZP 400 mg Q4W n=195 participants at risk 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.	All CZP 200 mg + 400 mg n=393 participants at risk 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.
Blood and lymphatic system disorders Splenomegaly	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Cardiac disorders Coronary artery thrombosis	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Cardiac disorders Angina unstable	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 2/393 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Cardiac disorders Myocardial infarction	1.0% 2/198 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 2/393 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Cardiac disorders Acute myocardial infarction	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Cardiac disorders Myocarditis	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Cardiac disorders Atrial fibrillation	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 2/393 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Cardiac disorders Cardiac arrest	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Ear and labyrinth disorders Tinnitus	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Eye disorders Cataract	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Eye disorders Diplopia	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Gastrointestinal disorders Abdominal hernia	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Gastrointestinal disorders Pancreatitis acute	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Gastrointestinal disorders Abdominal pain	0.51% 1/198 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Gastrointestinal disorders Crohn's disease	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Gastrointestinal disorders Hypoaesthesia oral	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
General disorders Sudden death	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
General disorders Pyrexia	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
General disorders Chest pain	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Hepatobiliary disorders Biliary colic	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Hepatobiliary disorders Cholelithiasis	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	1.0% 2/195 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.76% 3/393 • Number of events 3 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Hepatobiliary disorders Cholecystitis	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	1.0% 2/195 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 2/393 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Hepatobiliary disorders Biliary dyskinesia	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Diverticulitis	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Cellulitis	1.0% 2/198 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 2/393 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Arthritis bacterial	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Vascular disorders Haematoma	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Herpes zoster	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Device related infection	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Postoperative wound infection	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Pneumonia	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	1.5% 3/195 • Number of events 4 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	1.0% 4/393 • Number of events 5 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Bronchitis	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Bronchopneumonia	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations HIV infection	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 2/393 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Sepsis	0.00% 0/198 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 1/195 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Staphylococcal abscess	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Erysipelas	1.0% 2/198 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.51% 2/393 • Number of events 2 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Pyoderma streptococcal	0.51% 1/198 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.00% 0/195 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	0.25% 1/393 • Number of events 1 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.

Other adverse events
Measure	All CZP 200 mg Q2W n=198 participants at risk 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.	All CZP 400 mg Q4W n=195 participants at risk 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.	All CZP 200 mg + 400 mg n=393 participants at risk 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.
Gastrointestinal disorders Diarrhoea	7.6% 15/198 • Number of events 20 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.6% 11/195 • Number of events 15 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	6.6% 26/393 • Number of events 35 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Gastrointestinal disorders Abdominal pain	6.1% 12/198 • Number of events 13 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.6% 9/195 • Number of events 10 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.3% 21/393 • Number of events 23 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Gastrointestinal disorders Abdominal pain upper	7.1% 14/198 • Number of events 16 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	2.6% 5/195 • Number of events 9 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.8% 19/393 • Number of events 25 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Gastrointestinal disorders Nausea	5.1% 10/198 • Number of events 11 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.1% 8/195 • Number of events 9 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.6% 18/393 • Number of events 20 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Upper respiratory tract infection	22.2% 44/198 • Number of events 81 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	25.1% 49/195 • Number of events 73 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	23.7% 93/393 • Number of events 154 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Nasopharyngitis	22.7% 45/198 • Number of events 87 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	21.5% 42/195 • Number of events 91 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	22.1% 87/393 • Number of events 178 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Pharyngitis	12.1% 24/198 • Number of events 44 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	13.8% 27/195 • Number of events 37 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	13.0% 51/393 • Number of events 81 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Bronchitis	14.1% 28/198 • Number of events 36 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	11.3% 22/195 • Number of events 29 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	12.7% 50/393 • Number of events 65 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Urinary tract infection	6.6% 13/198 • Number of events 18 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	13.3% 26/195 • Number of events 35 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	9.9% 39/393 • Number of events 53 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Sinusitis	9.6% 19/198 • Number of events 32 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	6.7% 13/195 • Number of events 33 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	8.1% 32/393 • Number of events 65 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Gastroenteritis	7.1% 14/198 • Number of events 18 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.1% 8/195 • Number of events 8 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.6% 22/393 • Number of events 26 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Oral herpes	5.1% 10/198 • Number of events 25 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.6% 11/195 • Number of events 18 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.3% 21/393 • Number of events 43 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Influenza	6.6% 13/198 • Number of events 15 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.1% 8/195 • Number of events 9 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.3% 21/393 • Number of events 24 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Tonsillitis	5.6% 11/198 • Number of events 11 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.1% 8/195 • Number of events 12 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.8% 19/393 • Number of events 23 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Rhinitis	5.1% 10/198 • Number of events 11 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.6% 9/195 • Number of events 9 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.8% 19/393 • Number of events 20 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Latent tuberculosis	3.0% 6/198 • Number of events 6 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	6.2% 12/195 • Number of events 12 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.6% 18/393 • Number of events 18 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Infections and infestations Viral infection	4.5% 9/198 • Number of events 12 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	3.6% 7/195 • Number of events 7 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.1% 16/393 • Number of events 19 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Injury, poisoning and procedural complications Contusion	7.6% 15/198 • Number of events 21 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.6% 9/195 • Number of events 10 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	6.1% 24/393 • Number of events 31 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Investigations Alanine aminotransferase increased	8.6% 17/198 • Number of events 23 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	7.7% 15/195 • Number of events 25 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	8.1% 32/393 • Number of events 48 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Investigations Blood creatine phosphokinase increased	7.6% 15/198 • Number of events 28 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	6.7% 13/195 • Number of events 25 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	7.1% 28/393 • Number of events 53 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Investigations Aspartate aminotransferase increased	4.5% 9/198 • Number of events 13 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.6% 11/195 • Number of events 17 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.1% 20/393 • Number of events 30 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Investigations Gamma-glutamyltransferase increased	4.0% 8/198 • Number of events 11 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	6.2% 12/195 • Number of events 15 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.1% 20/393 • Number of events 26 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Musculoskeletal and connective tissue disorders Back pain	12.1% 24/198 • Number of events 28 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	11.3% 22/195 • Number of events 26 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	11.7% 46/393 • Number of events 54 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Musculoskeletal and connective tissue disorders Psoriatic arthropathy	12.1% 24/198 • Number of events 41 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	7.7% 15/195 • Number of events 23 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	9.9% 39/393 • Number of events 64 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Musculoskeletal and connective tissue disorders Arthralgia	10.1% 20/198 • Number of events 28 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	9.2% 18/195 • Number of events 28 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	9.7% 38/393 • Number of events 56 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Nervous system disorders Headache	9.1% 18/198 • Number of events 19 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	8.7% 17/195 • Number of events 20 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	8.9% 35/393 • Number of events 39 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Nervous system disorders Dizziness	2.5% 5/198 • Number of events 5 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.1% 10/195 • Number of events 10 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	3.8% 15/393 • Number of events 15 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Psychiatric disorders Depression	5.6% 11/198 • Number of events 12 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.6% 9/195 • Number of events 12 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.1% 20/393 • Number of events 24 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Respiratory, thoracic and mediastinal disorders Cough	4.0% 8/198 • Number of events 9 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	7.2% 14/195 • Number of events 14 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.6% 22/393 • Number of events 23 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.0% 6/198 • Number of events 6 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	5.1% 10/195 • Number of events 13 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.1% 16/393 • Number of events 19 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Skin and subcutaneous tissue disorders Psoriasis	11.1% 22/198 • Number of events 31 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	9.7% 19/195 • Number of events 21 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	10.4% 41/393 • Number of events 52 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Skin and subcutaneous tissue disorders Rash	5.1% 10/198 • Number of events 16 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.6% 9/195 • Number of events 9 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	4.8% 19/393 • Number of events 25 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.
Vascular disorders Hypertension	15.2% 30/198 • Number of events 33 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	8.2% 16/195 • Number of events 20 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.	11.7% 46/393 • Number of events 53 • Adverse Events (AEs) were collected from Baseline (Week 0) over the whole Double-Blind, Dose-Blind and Open-Label Period up to Week 216. 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.