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Clinical Trial Results:
MULTICENTER, OPEN-LABEL (PART A) FOLLOWED BY A RANDOMIZED, DOUBLE-BLIND, PARALLEL-GROUP, PLACEBO-CONTROLLED STUDY (PART B) TO EVALUATE MAINTENANCE OF REMISSION IN SUBJECTS WITH ACTIVE AXIAL SPONDYLOARTHRITIS (AXSPA) RECEIVING EITHER CERTOLIZUMAB PEGOL 200MG Q2W OR 200MG Q4W AS COMPARED TO PLACEBO

Summary
EudraCT number	2015-000339-34
Trial protocol	HU BE CZ DE GB ES NL FR RO PL BG
Global end of trial date	23 Apr 2019

Results information
Results version number	v1(current)
This version publication date	08 May 2020
First version publication date	08 May 2020
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

AS0005

ISRCTN number

US NCT number

NCT02505542

WHO universal trial number (UTN)

Sponsor organisation name

UCB BIOSCIENCES GmbH

Sponsor organisation address

Alfred-Nobel-Strasse 10, Monheim, Germany, 40789

Public contact

Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com

Scientific contact

Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

09 May 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

23 Apr 2019

Was the trial ended prematurely?

Main objective of the trial

To evaluate the percentage of subjects who do not experience a flare on CZP 200 mg Q2W (full dose) or 200 mg Q4W (half-dose) as compared to placebo (CZP withdrawal) during Part B

Protection of trial subjects

During the conduct of the study all study participants were closely monitored.

Background therapy

Background therapy as permitted and stated in the protocol.

Evidence for comparator

Not Applicable

Actual start date of recruitment

31 Jul 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 5

Country: Number of subjects enrolled

Taiwan: 34

Country: Number of subjects enrolled

Turkey: 41

Country: Number of subjects enrolled

United Kingdom: 6

Country: Number of subjects enrolled

United States: 33

Country: Number of subjects enrolled

Belgium: 25

Country: Number of subjects enrolled

Bulgaria: 59

Country: Number of subjects enrolled

Czech Republic: 214

Country: Number of subjects enrolled

France: 9

Country: Number of subjects enrolled

Germany: 40

Country: Number of subjects enrolled

Hungary: 46

Country: Number of subjects enrolled

Netherlands: 6

Country: Number of subjects enrolled

Poland: 184

Country: Number of subjects enrolled

Romania: 34

Worldwide total number of subjects

736

EEA total number of subjects

628

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

736

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study started to enroll patients in July 2015 and concluded in April 2019.

Screening details

The study included 2 parts: Part A with a Screening Period (up to 5 Weeks) and an Open-Label Period (Week 0 to Week 48) and Part B with a Double-Blind Period (Week 48 to Week 96) and a Safety Follow-Up Period (10 weeks after the last dose of study medication). Participant Flow refers to the Open-Label Set.

Period 1 title

Part A: Open-Label Period

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Certolizumab pegol Open-Label

Arm description

Participants in this arm 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 to Week 48 (Part A). Participants in sustained remission at Week 48 were eligible for randomization into Part B.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Certolizumab pegol (CZP) 400 mg or 200 mg were administered as subcutaneous (sc) injections every 2 weeks (Q2W) (full-dose) or every 4 weeks (Q4W) (half-dose). Suitable areas for administrations were the lateral abdominal wall and upper outer thigh. Study medication should have been administered with a minimum of 10 days between the CZP 200 mg Q2W administrations.

Number of subjects in period 1	Certolizumab pegol Open-Label
Started	736
Completed	659
Not completed	77
Participant did not attend week 48 visit	1
Consent withdrawn by subject	27
New medical history available	1
Adverse event, non-fatal	31
Screening failure (detected too late)	1
Sponsor directive	1
Pregnancy	2
Non-compliance	1
Medical monitor decision	1
Lost to follow-up	5
Lack of efficacy	5
Protocol deviation	1

Period 2 title

Completed Part A, did not enter Part B

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Certolizumab pegol Open-Label

Arm description

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 2	Certolizumab pegol Open-Label
Started	659
Completed	313
Not completed	346
Consent withdrawn by subject	3
The subject was not eligible for Part B	341
Lack of efficacy	2

Period 3 title

Part B: Double-Blind Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Blinding implementation details

Subjects who flared were given escape treatment until the end of the study.

Are arms mutually exclusive

Yes

Placebo Double-Blind

Arm description

Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

PBO

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Matching Placebo was administered as subcutaneous (sc) injections every 2 weeks (Q2W) or to maintain the study blind.

Certolizumab pegol 200 mg Q2W Double-Blind

Arm description

Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Certolizumab pegol 200 mg Q4W Double-Blind

Arm description

Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 4 weeks (Q4W) from Week 48 onwards. At visits where CZP was not received, subjects received one injection of Placebo to maintain the study blind.

Arm type

Experimental

Investigational medicinal product name

Certolizumab pegol

Investigational medicinal product code

CZP

Other name

Cimzia

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Investigational medicinal product name

Placebo

Investigational medicinal product code

PBO

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Matching Placebo was administered as subcutaneous (sc) injections every 2 weeks (Q2W) or to maintain the study blind.

Number of subjects in period 3	Placebo Double-Blind	Certolizumab pegol 200 mg Q2W Double-Blind	Certolizumab pegol 200 mg Q4W Double-Blind
Started	104	104	105
Started Escape Period	73 ^[1]	7 ^[2]	15 ^[3]
Completed	92	95	98
Not completed	12	9	7
Consent withdrawn by subject	8	7	2
Miscalculation	1	-	-
Adverse event, non-fatal	-	1	3
Patient was moved from the country	-	-	1
Subject did not complete all visits	1	-	-
Lost to follow-up	-	-	1
Week 94 missed	-	1	-
Planning pregnancy	1	-	-
Lack of efficacy	1	-	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Number of participants at the milestones reflects those who experienced a flare during the Double-Blind Period and escaped to full-dose treatment until the end of that period or for at least 12 weeks, whichever is longer.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Number of participants at the milestones reflects those who experienced a flare during the Double-Blind Period and escaped to full-dose treatment until the end of that period or for at least 12 weeks, whichever is longer.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Number of participants at the milestones reflects those who experienced a flare during the Double-Blind Period and escaped to full-dose treatment until the end of that period or for at least 12 weeks, whichever is longer.

Baseline characteristics

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Reporting group title

Certolizumab pegol Open-Label

Reporting group description

Reporting group values	Certolizumab pegol Open-Label	Total
Number of subjects	736	736
Age categorical
Units: Subjects
<=18 years	7	7
Between 18 and 65 years	729	729
>=65 years	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	32.9 ± 7.0	-
Gender categorical
Units: Subjects
Male	514	514
Female	222	222

End points

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Reporting group title

Certolizumab pegol Open-Label

Reporting group description

Reporting group title

Certolizumab pegol Open-Label

Reporting group description

Reporting group title

Placebo Double-Blind

Reporting group description

Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.

Reporting group title

Certolizumab pegol 200 mg Q2W Double-Blind

Reporting group description

Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.

Reporting group title

Certolizumab pegol 200 mg Q4W Double-Blind

Reporting group description

Subject analysis set title

Placebo Double-Blind (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards. Participants formed the Randomized Set (RS).

Subject analysis set title

Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards. Participants formed the RS.

Subject analysis set title

Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Certolizumab pegol Open-Label (OLS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Placebo DB/CZP 200 mg Q2W Escape (FS)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants randomized to Placebo who met flare criteria received CZP 400 mg subcutaneous (sc) every 2 weeks (Q2W) for the first 3 visits after flare has been confirmed. After that, CZP 200 mg was given every 2 weeks in open-label fashion. The duration was from starting escape treatment after flare until Week 96 with a minimum of 12 weeks. Participants formed the Flared Set (FS).

Subject analysis set title

CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants randomized to CZP 200 mg Q2W who meet flare criteria received CZP 200 mg subcutaneous (sc) every 2 weeks (Q2W) for all visits after flare has been confirmed. At the first 3 visits after flare has been confirmed, participants received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind. The duration was from starting escape treatment after flare until Week 96 with a minimum of 12 weeks. Participants formed the FS.

Subject analysis set title

CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants randomized to CZP 200 mg Q4W who meet flare criteria received CZP 200 mg subcutaneous (sc) every 2 weeks (Q2W) for all visits after flare has been confirmed. At the first 3 visits after flare has been confirmed, participants received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind. The duration was from starting escape treatment after flare until Week 96 with a minimum of 12 weeks. Participants formed the FS.

Subject analysis set title

Certolizumab pegol Open-Label (SS) Wk 0-48

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Placebo Double-Blind (SSB) Wk 48–96

Subject analysis set type

Safety analysis

Subject analysis set description

Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards. Participants formed the Safety Set Part B (SSB).

Subject analysis set title

Certolizumab pegol 200 mg Q2W Double-Blind (SSB) Wk 48–96

Subject analysis set type

Safety analysis

Subject analysis set description

Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards. Participants formed the SSB.

Subject analysis set title

Certolizumab pegol 200 mg Q4W Double-Blind (SSB) Wk 48–96

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Placebo DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Placebo Double-Blind (PKSB)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards. Participants formed the Pharmacokinetic Set B (PKSB).

Subject analysis set title

Certolizumab pegol 200 mg Q2W Double-Blind (PKSB)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards. Participants formed the PKSB.

Subject analysis set title

Certolizumab pegol 200 mg Q4W Double-Blind (PKSB)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: Percentage of participants in Part B who did not experienced a flare

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End point title

Percentage of participants in Part B who did not experienced a flare

End point description

A participant was considered to have experienced a flare if the participant had an Ankylosing spondylitis disease activity score (ASDAS) greater or equal to (≥) 2.1 at 2 consecutive visits or an ASDAS greater than (>) 3.5 at any visit during Part B up until Week 96. A participant qualified for Part B only if he achieved sustained remission after 48 weeks of Open-Label certolizumab pegol (CZP) treatment. Sustained remission was achieved when a participant had an ASDAS less than (<) 1.3 at Week 32 or Week 36 (if ASDAS < 1.3 at Week 32, it must have been < 2.1 at Week 36; if ASDAS < 2.1 at Week 32, it must have been < 1.3 at Week 36) and an ASDAS < 1.3 at Week 48. Missing data were handled using non-response imputation (NRI) methods.

End point type

Primary

End point timeframe

From Week 48 to Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: percentage of participants
number (confidence interval 95%)	20.2 (13.0 to 29.2)	83.7 (75.1 to 90.2)	79.0 (70.0 to 86.4)

Statistical analysis 1

Statistical analysis description

Odds ratio (and corresponding p-value) resulted from a logistic regression model with factors for treatment, geographic region, and modified New York (mNY) classification for study participants who did not experience a flare. An odds ratio > 1 indicates a study participant on CZP was more likely not to experience a flare than a study participant on placebo. Penalized maximum likelihood approach was used for logistic regression.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[1]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

18.822

Confidence interval

level

95%

sides

2-sided

lower limit

9.605

upper limit

38.864

Notes
[1] - A fixed sequence testing procedure was used whereby the second test (CZP 200 mg Q4W vs PBO) was interpreted as statistically significant only if the first test (CZP 200 mg Q2W vs PBO) was significant at the 0.05 level as well.

Statistical analysis 2

Statistical analysis description

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[2]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

14.069

Confidence interval

level

95%

sides

2-sided

lower limit

7.395

upper limit

27.955

Notes
[2] - A fixed sequence testing procedure was used whereby the second test (CZP 200 mg Q4W vs PBO) was interpreted as statistically significant only if the first test (CZP 200 mg Q2W vs PBO) was significant at the 0.05 level as well.

Secondary: Percentage of participants achieving sustained remission at Week 48 in Part A

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End point title

Percentage of participants achieving sustained remission at Week 48 in Part A

End point description

Sustained remission was achieved when a participant had an ASDAS less than (<) 1.3 at Week 32 or Week 36 (if ASDAS < 1.3 at Week 32, it must have been < 2.1 at Week 36; if ASDAS < 2.1 at Week 32, it must have been < 1.3 at Week 36) and an ASDAS < 1.3 at Week 48. Missing data were handled using non-response imputation (NRI) methods.

End point type

Secondary

End point timeframe

Week 48

End point values	Certolizumab pegol Open-Label (OLS)
Number of subjects analysed	736
Units: percentage of participants
number (confidence interval 95%)	43.9 (40.3 to 47.6)

No statistical analyses for this end point

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Week 48 in Part A

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End point title

Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Week 48 in Part A

End point description

The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Disease activity was measured by categorical response variables: • ASDAS-Inactive Disease (ASDAS-ID): ASDAS < 1.3 • ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, < 2.1 • ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5 • ASDAS-very High Disease activity (ASDAS-vHD): ASDAS > 3.5 Missing data were handled using last observation carried forward (LOCF) methods.

End point type

Secondary

End point timeframe

Week 48

End point values	Certolizumab pegol Open-Label (OLS)
Number of subjects analysed	736
Units: percentage of participants
number (not applicable)
ASDAS-ID	52.5
ASDAS-MD	22.8
ASDAS-HD	18.9
ASDAS-vHD	5.9

No statistical analyses for this end point

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Week 48 in Part A

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End point title

Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Week 48 in Part A

End point description

The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). ASDAS improvement was measured by binary response variables: • ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline • ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline Missing data were handled using non-response imputation (NRI) methods.

End point type

Secondary

End point timeframe

Week 48

End point values	Certolizumab pegol Open-Label (OLS)
Number of subjects analysed	736
Units: percentage of participants
number (not applicable)
ASDAS-CII	76.6
ASDAS-MI	56.1

No statistical analyses for this end point

Secondary: Time to flare in Part B

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End point title

Time to flare in Part B

End point description

For those who met the criteria for flare (see primary efficacy variable), the time to flare was the length in days from randomization in Part B until the visit at which the criteria for flare were met. Participants who discontinued the study without meeting the criteria for flare were counted as experiencing a flare at the time of their last study visit. The time to flare was analyzed using Kaplan-Meier methods. If Kaplan-Meier Estimate was NA for all estimates then more than 75 % failed to meet the flare condition. Missing data were handled using non-response imputation (NRI) methods. Note: 999 was used as a placeholder for values that were not calculated since more than 75 % failed to meet the flare condition.

End point type

Secondary

End point timeframe

From Week 48 to Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: days
median (inter-quartile range (Q1-Q3))	113 (84 to 257)	371 (371 to 371)	999 (999 to 999)

Statistical analysis 1

Statistical analysis description

P-values were from stratified log-rank test comparing the Certolizumab pegol 200 mg Q2W Double-Blind (RS) group with the Placebo Double-Blind (RS) group (Geographic region and modified New York (mNY) classification were used as stratification factors).

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Logrank

Confidence interval

Statistical analysis 2

Statistical analysis description

P-values were from stratified log-rank test comparing the Certolizumab pegol 200 mg Q4W Double-Blind (RS) group with the Placebo Double-Blind (RS) group (Geographic region and modified New York (mNY) classification were used as stratification factors).

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Logrank

Confidence interval

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Week 96 in Part B

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End point title

Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Week 96 in Part B

End point description

End point type

Secondary

End point timeframe

Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: percentage of participants
number (not applicable)
ASDAS-ID	58.3	86.2	69.9
ASDAS-MD	25.0	13.8	22.9
ASDAS-HD	16.7	0	7.2
ASDAS-vHD	0	0	0

No statistical analyses for this end point

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Week 96 in Part B

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End point title

Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Week 96 in Part B

End point description

The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). ASDAS improvement was measured by binary response variables: • ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline • ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline Missing data were handled using non-response imputation (NRI) methods.

End point type

Secondary

End point timeframe

Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: percentage of participants
number (not applicable)
ASDAS-CII	21.2	82.7	75.2
ASDAS-MI	10.6	67.3	58.1

Statistical analysis 1

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and modified New York (mNY) classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

17.94

Confidence interval

level

95%

sides

2-sided

lower limit

8.95

upper limit

35.961

Statistical analysis 2

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and modified New York (mNY) classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

11.385

Confidence interval

level

95%

sides

2-sided

lower limit

5.952

upper limit

21.778

Statistical analysis 3

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and modified New York (mNY) classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

17.653

Confidence interval

level

95%

sides

2-sided

lower limit

8.333

upper limit

37.399

Statistical analysis 4

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and modified New York (mNY) classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

11.863

Confidence interval

level

95%

sides

2-sided

lower limit

5.67

upper limit

24.822

Secondary: Percentage of participants with Axial SpondyloArthritis International Society 20 % response criteria (ASAS20) response at Week 96 in Part B

Top of page

End point title

Percentage of participants with Axial SpondyloArthritis International Society 20 % response criteria (ASAS20) response at Week 96 in Part B

End point description

The ASAS20 response was defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit]. Missing data were handled using non-response imputation (NRI) methods.

End point type

Secondary

End point timeframe

Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: percentage of participants
number (not applicable)	23.1	85.6	78.1

Statistical analysis 1

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

20.205

Confidence interval

level

95%

sides

2-sided

lower limit

9.851

upper limit

41.439

Statistical analysis 2

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

12.07

Confidence interval

level

95%

sides

2-sided

lower limit

6.275

upper limit

23.218

Secondary: Percentage of participants with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) response at Week 96 in Part B

Top of page

End point title

Percentage of participants with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) response at Week 96 in Part B

End point description

The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. Missing data were handled using non-response imputation (NRI) methods.

End point type

Secondary

End point timeframe

Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: percentage of participants
number (not applicable)	21.2	84.6	73.3

Statistical analysis 1

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

20.891

Confidence interval

level

95%

sides

2-sided

lower limit

10.21

upper limit

42.744

Statistical analysis 2

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

10.377

Confidence interval

level

95%

sides

2-sided

lower limit

5.456

upper limit

19.738

Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) 5/6 response criteria response at Week 96 in Part B

Top of page

End point title

Percentage of participants with Axial SpondyloArthritis International Society (ASAS) 5/6 response criteria response at Week 96 in Part B

End point description

The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP). Missing data were handled using non-response imputation (NRI) methods.

End point type

Secondary

End point timeframe

Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: percentage of participants
number (not applicable)	12.5	70.2	62.9

Statistical analysis 1

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

16.9

Confidence interval

level

95%

sides

2-sided

lower limit

8.211

upper limit

34.785

Statistical analysis 2

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

12.072

Confidence interval

level

95%

sides

2-sided

lower limit

5.954

upper limit

24.476

Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) partial remission (PR) response criteria response at Week 96 in Part B

Top of page

End point title

Percentage of participants with Axial SpondyloArthritis International Society (ASAS) partial remission (PR) response criteria response at Week 96 in Part B

End point description

The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20. Missing data were handled using non-response imputation (NRI) methods.

End point type

Secondary

End point timeframe

Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: percentage of participants
number (not applicable)	17.3	77.9	70.5

Statistical analysis 1

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

17.082

Confidence interval

level

95%

sides

2-sided

lower limit

8.561

upper limit

34.085

Statistical analysis 2

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

11.503

Confidence interval

level

95%

sides

2-sided

lower limit

5.939

upper limit

22.278

Secondary: Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B

Top of page

End point title

Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B

End point description

The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). There is a minimum score of 0.636 for the total ASDAS score, but no defined upper score. Based on the formula even in the situation that the CRP is normal, any value below 4 is recorded as “below the limit of quantification” (BLQ) and a value of BLQ/2=2 was prespecified. This assumption is triggering the lowest possible value of 0.636. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.

End point type

Secondary

End point timeframe

From Week 48 to Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: scores on a scale
least squares mean (standard error)	1.66 ± 0.110	0.24 ± 0.077	0.45 ± 0.077

Statistical analysis 1

Statistical analysis description

An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference vs Placebo

Point estimate

-1.42

Confidence interval

level

95%

sides

2-sided

lower limit

-1.66

upper limit

-1.17

Variability estimate

Standard error of the mean

Dispersion value

0.126

Statistical analysis 2

Statistical analysis description

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference vs Placebo

Point estimate

-1.21

Confidence interval

level

95%

sides

2-sided

lower limit

-1.45

upper limit

-0.96

Variability estimate

Standard error of the mean

Dispersion value

0.126

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B

Top of page

End point title

Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B

End point description

The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.

End point type

Secondary

End point timeframe

From Week 48 to Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: scores on a scale
least squares mean (standard error)	3.02 ± 0.226	0.56 ± 0.176	0.78 ± 0.176

Statistical analysis 1

Statistical analysis description

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference vs Placebo

Point estimate

-2.46

Confidence interval

level

95%

sides

2-sided

lower limit

-2.99

upper limit

-1.94

Variability estimate

Standard error of the mean

Dispersion value

0.268

Statistical analysis 2

Statistical analysis description

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference vs Placebo

Point estimate

-2.24

Confidence interval

level

95%

sides

2-sided

lower limit

-2.77

upper limit

-1.72

Variability estimate

Standard error of the mean

Dispersion value

0.267

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B

Top of page

End point title

Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B

End point description

The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.

End point type

Secondary

End point timeframe

From Week 48 to Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: scores on a scale
least squares mean (standard error)	1.90 ± 0.233	0.32 ± 0.198	0.46 ± 0.205

Statistical analysis 1

Statistical analysis description

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference vs Placebo

Point estimate

-1.57

Confidence interval

level

95%

sides

2-sided

lower limit

-2.04

upper limit

-1.11

Variability estimate

Standard error of the mean

Dispersion value

0.238

Statistical analysis 2

Statistical analysis description

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean Difference vs Placebo

Point estimate

-1.43

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

-0.96

Variability estimate

Standard error of the mean

Dispersion value

0.238

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B

Top of page

End point title

Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B

End point description

The BASMI is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.

End point type

Secondary

End point timeframe

From Week 48 to Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: scores on a scale
least squares mean (standard error)	0.21 ± 0.105	0.00 ± 0.065	-0.03 ± 0.068

Statistical analysis 1

Statistical analysis description

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.074

Method

Mixed models analysis

Parameter type

LS Mean Difference vs Placebo

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.112

Statistical analysis 2

Statistical analysis description

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.036

Method

Mixed models analysis

Parameter type

LS Mean Difference vs Placebo

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.46

upper limit

-0.02

Variability estimate

Standard error of the mean

Dispersion value

0.113

Secondary: Percentage of participants with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response criteria response at Week 96 in Part B

Top of page

End point title

Percentage of participants with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response criteria response at Week 96 in Part B

End point description

The BASDAI50 response was defined as an improvement of at least 50 % in the BASDAI score relative to Baseline. Missing data were handled using non-response imputation (NRI) methods.

End point type

Secondary

End point timeframe

Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	104	104	105
Units: percentage of participants
number (not applicable)	22.1	83.7	77.1

Statistical analysis 1

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

18.308

Confidence interval

level

95%

sides

2-sided

lower limit

9.084

upper limit

36.898

Statistical analysis 2

Statistical analysis description

Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

12.02

Confidence interval

level

95%

sides

2-sided

lower limit

6.255

upper limit

23.098

Secondary: Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) score at Week 96 in Part B

Top of page

End point title

Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) score at Week 96 in Part B

End point description

The SPARCC scoring method for lesions found on the Magnetic Resonance Imaging (MRI) is based on an abnormal increased signal on the Short-Tau-Inversion Recovery (STIR) sequence, representing bone marrow edema. Total Sacroiliac (SI) joint SPARCC score can range from 0 to 72 with higher scores indicating higher joint inflammation. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.

End point type

Secondary

End point timeframe

From Week 48 to Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	24	79	77
Units: scores on a scale
arithmetic mean (standard deviation)	1.1 ± 3.6	0.2 ± 2.4	0.6 ± 3.8

Statistical analysis 1

Statistical analysis description

Only MRIs performed ± 2 weeks around the Week 96 or Early Withdrawal Visit were assigned to Week 96 or Early Withdrawal. Only results of the double-read assessments of the central MRI review were included. The analysis used the average of the scores from the 2 independent reviewers. Whenever an adjudication was present, the average score across all 3 reviewers was used. ANCOVA model with treatment, geographical region, mNY classification, and Part B Baseline as covariates.

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.195

Method

ANCOVA

Parameter type

LS Mean Difference vs Placebo

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

0.51

Variability estimate

Standard error of the mean

Dispersion value

0.76

Statistical analysis 2

Statistical analysis description

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.432

Method

ANCOVA

Parameter type

LS Mean Difference vs Placebo

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.11

upper limit

0.91

Variability estimate

Standard error of the mean

Dispersion value

0.76

Secondary: Change from Baseline in spine Ankylosing Spondylitis spine Magnetic Resonance Imaging Score for Disease activity (ASspIMRI-a) in the Berlin modification score at Week 96 in Part B

Top of page

End point title

Change from Baseline in spine Ankylosing Spondylitis spine Magnetic Resonance Imaging Score for Disease activity (ASspIMRI-a) in the Berlin modification score at Week 96 in Part B

End point description

The Berlin modification of the ASspiMRI-a is a scoring system with a concentration on Short-Tau-Inversion Recovery (STIR) sequences without other fat saturation techniques. It quantifies changes in 23 Vertebral Units (VU) of the spine. Active inflammation was scored by grading the degree of bone marrow edema from 0 to 3 in 1 dimension on 1 or more consecutive slices that represent the highest level of inflammation in a particular VU. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.

End point type

Secondary

End point timeframe

From Week 48 to Week 96

End point values	Placebo Double-Blind (RS)	Certolizumab pegol 200 mg Q2W Double-Blind (RS)	Certolizumab pegol 200 mg Q4W Double-Blind (RS)
Number of subjects analysed	24	79	78
Units: scores on a scale
arithmetic mean (standard deviation)	0.4 ± 0.9	0.0 ± 0.8	0.0 ± 0.8

Statistical analysis 1

Statistical analysis description

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.04

Method

ANCOVA

Parameter type

LS Mean Difference vs Placebo

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.78

upper limit

-0.02

Variability estimate

Standard error of the mean

Dispersion value

0.19

Statistical analysis 2

Statistical analysis description

Comparison groups

Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.074

Method

ANCOVA

Parameter type

LS Mean Difference vs Placebo

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

0.03

Variability estimate

Standard error of the mean

Dispersion value

0.19

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Escape Week 12 for participants who experienced a flare in Part B

Top of page

End point title

Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Escape Week 12 for participants who experienced a flare in Part B

End point description

End point type

Secondary

End point timeframe

Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
Number of subjects analysed	73	7	15
Units: percentage of participants
number (not applicable)
ASDAS-ID	63.4	16.7	60.0
ASDAS-MD	26.8	50.0	20.0
ASDAS-HD	8.5	33.3	20.0
ASDAS-vHD	1.4	0	0

No statistical analyses for this end point

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Escape Week 12 for participants who experienced a flare in Part B

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End point title

Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Escape Week 12 for participants who experienced a flare in Part B

End point description

The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). ASDAS improvement was measured by binary response variables: • ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline • ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline

End point type

Secondary

End point timeframe

Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
Number of subjects analysed	73	7	15
Units: percentage of participants
number (not applicable)
ASDAS-CII	84.5	16.7	46.7
ASDAS-MI	49.3	0	13.3

No statistical analyses for this end point

Secondary: Percentage of participants with Axial SpondyloArthritis International Society 20 % response criteria (ASAS20) response at Escape Week 12 for participants who experienced a flare in Part B

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End point title

Percentage of participants with Axial SpondyloArthritis International Society 20 % response criteria (ASAS20) response at Escape Week 12 for participants who experienced a flare in Part B

End point description

End point type

Secondary

End point timeframe

Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
Number of subjects analysed	73	7	15
Units: percentage of participants
number (not applicable)	83.3	50.0	64.3

No statistical analyses for this end point

Secondary: Percentage of participants with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) response at Escape Week 12 for participants who experienced a flare in Part B

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End point title

Percentage of participants with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) response at Escape Week 12 for participants who experienced a flare in Part B

End point description

End point type

Secondary

End point timeframe

Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
Number of subjects analysed	73	7	15
Units: percentage of participants
number (not applicable)	69.4	16.7	50.0

No statistical analyses for this end point

Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) 5/6 response criteria response at Escape Week 12 for participants who experienced a flare in Part B

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End point title

Percentage of participants with Axial SpondyloArthritis International Society (ASAS) 5/6 response criteria response at Escape Week 12 for participants who experienced a flare in Part B

End point description

End point type

Secondary

End point timeframe

Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
Number of subjects analysed	73	7	15
Units: percentage of participants
number (not applicable)	60.6	16.7	7.1

No statistical analyses for this end point

Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) partial remission (PR) response criteria response at Escape Week 12 for participants who experienced a flare in Part B

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End point title

Percentage of participants with Axial SpondyloArthritis International Society (ASAS) partial remission (PR) response criteria response at Escape Week 12 for participants who experienced a flare in Part B

End point description

The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.

End point type

Secondary

End point timeframe

Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
Number of subjects analysed	73	7	15
Units: percentage of participants
number (not applicable)	66.7	16.7	50.0

No statistical analyses for this end point

Secondary: Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for participants who experienced a flare in Part B

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End point title

Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for participants who experienced a flare in Part B

End point description

The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). There is a minimum score of 0.636 for the total ASDAS score, but no defined upper score. Based on the formula even in the situation that the CRP is normal, any value below 4 is recorded as “below the limit of quantification” (BLQ) and a value of BLQ/2=2 was prespecified. This assumption is triggering the lowest possible value of 0.636. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.

End point type

Secondary

End point timeframe

From time of flare to Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
Number of subjects analysed	71	6	15
Units: scores on a scale
arithmetic mean (standard deviation)	-2.18 ± 1.13	-0.56 ± 0.64	-0.83 ± 0.94

No statistical analyses for this end point

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for participants who experienced a flare in Part B

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End point title

Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for participants who experienced a flare in Part B

End point description

The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.

End point type

Secondary

End point timeframe

From time of flare to Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
Number of subjects analysed	72	6	15
Units: scores on a scale
arithmetic mean (standard deviation)	-3.75 ± 2.52	-1.55 ± 1.05	-2.29 ± 2.35

No statistical analyses for this end point

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for participants who experienced a flare in Part B

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End point title

Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for participants who experienced a flare in Part B

End point description

The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.

End point type

Secondary

End point timeframe

From time of flare to Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
Number of subjects analysed	72	6	14
Units: scores on a scale
arithmetic mean (standard deviation)	-2.52 ± 2.46	-0.72 ± 0.70	-1.83 ± 2.38

No statistical analyses for this end point

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for participants who experienced a flare in Part B

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End point title

Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for participants who experienced a flare in Part B

End point description

The BASMI is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.

End point type

Secondary

End point timeframe

From time of flare to Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
Number of subjects analysed	67	6	15
Units: scores on a scale
arithmetic mean (standard deviation)	-0.43 ± 0.58	-0.27 ± 0.35	-0.26 ± 0.30

No statistical analyses for this end point

Secondary: Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) score at Escape Week 12 for participants who experienced a flare in Part B

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End point title

Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) score at Escape Week 12 for participants who experienced a flare in Part B

End point description

The SPARCC scoring method for lesions found on the Magnetic Resonance Imaging (MRI) is based on an abnormal increased signal on the Short-Tau-Inversion Recovery (STIR) sequence, representing bone marrow edema. Total Sacroiliac (SI) joint SPARCC score can range from 0 to 72 with higher scores indicating higher joint inflammation. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.

End point type

Secondary

End point timeframe

From time of flare to Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
Number of subjects analysed	48	2	12
Units: scores on a scale
arithmetic mean (standard deviation)	-9.3 ± 13.2	0.0 ± 0.0	0.2 ± 3.1

No statistical analyses for this end point

Secondary: Change from Baseline in spine Ankylosing Spondylitis spine Magnetic Resonance Imaging Score for activity (ASspIMRI-a) in the Berlin modification score at Escape Week 12 for participants who experienced a flare in Part B

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End point title

Change from Baseline in spine Ankylosing Spondylitis spine Magnetic Resonance Imaging Score for activity (ASspIMRI-a) in the Berlin modification score at Escape Week 12 for participants who experienced a flare in Part B

End point description

The Berlin modification of the ASspiMRI-a is a scoring system with a concentration on Short-Tau-Inversion Recovery (STIR) sequences without other fat saturation techniques. It quantifies changes in 23 Vertebral Units (VU) of the spine. Active inflammation was scored by grading the degree of bone marrow edema from 0 to 3 in 1 dimension on 1 or more consecutive slices that represent the highest level of inflammation in a particular VU. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.

End point type

Secondary

End point timeframe

From time of flare to Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
Number of subjects analysed	48	2	12
Units: scores on a scale
arithmetic mean (standard deviation)	-2.3 ± 4.6	0.0 ± 0.0	-0.3 ± 1.0

No statistical analyses for this end point

Secondary: Certolizumab pegol (CZP) Plasma Concentration during the study

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End point title

Certolizumab pegol (CZP) Plasma Concentration during the study

End point description

CZP plasma concentration was measured in micrograms per milliliter (μg/mL). Blood sample measurements that were deemed to be below the level of quantification, were set to half the lower level of quantification (LLOQ) for analysis purposes. Summary statistics were only displayed if at least two-thirds of the values were above the LLOQ and if n was greater or equal to (>=) 4. The primary purpose of the study was to evaluate treatment options for axSpA patients after being in sustained remission. Hence, one of the objectives was to evaluate the PK of these patients. The CZP plasma concentration of the patients that did not reach sustained remission were therefore not analysed, and the Pharmacokinetic Set A as described in the protocol was removed from the SAP. Note: Number of participants analyzed each Week is presented in parentheses following the model: (PBO, CZP 200 mg Q2W, CZP 200 mg Q4W). 999 is used as a placeholder for values below the level of detection.

End point type

Secondary

End point timeframe

From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)

End point values	Placebo Double-Blind (PKSB)	Certolizumab pegol 200 mg Q2W Double-Blind (PKSB)	Certolizumab pegol 200 mg Q4W Double-Blind (PKSB)
Number of subjects analysed	101	102	105
Units: μg/mL
geometric mean (geometric coefficient of variation)
Part A Baseline (99, 101, 105)	999 ± 999	999 ± 999	999 ± 999
Week 4 (101, 100, 104)	48.71 ± 85.76	53.39 ± 30.93	48.92 ± 43.17
Week 12 (100, 101, 105)	30.91 ± 89.23	31.74 ± 50.79	30.69 ± 56.82
Week 24 (100, 101, 104)	26.31 ± 135.58	30.23 ± 46.57	28.96 ± 58.38
Week 48/Part B Baseline (98, 100, 104)	36.28 ± 74.18	36.59 ± 84.36	31.11 ± 138.29
Week 60 (98, 100, 105)	999 ± 999	27.76 ± 49.47	6.95 ± 178.27
Week 72 (76, 95, 99)	999 ± 999	26.36 ± 105.58	7.61 ± 176.39
Week 84 (38, 91, 90)	999 ± 999	26.57 ± 44.90	8.00 ± 113.48
Week 96 (27, 86, 85)	999 ± 999	24.76 ± 97.60	7.16 ± 131.76
Withdrawal Visit (4, 3, 5)	0.81 ± 1802.40	999 ± 999	0.30 ± 2621.06
Escape Week 0/Flare Baseline (72, 6, 14)	999 ± 999	30.77 ± 19.78	12.70 ± 98.45
Escape Week 2 (71, 6, 15)	18.27 ± 488.45	33.50 ± 21.17	15.43 ± 124.10
Escape Week 4 (71, 6, 15)	37.32 ± 151.18	32.94 ± 30.48	18.43 ± 79.93
Escape Week 12 (69, 6, 15)	23.89 ± 232.36	23.76 ± 65.42	19.14 ± 136.22
Escape Week 24 (54, 3, 8)	27.47 ± 45.31	999 ± 999	19.23 ± 66.68
Escape Week 36 (14, 3, 3)	24.88 ± 77.53	999 ± 999	999 ± 999
Last Visit (Week 96) (66, 6, 14)	24.64 ± 112.75	26.19 ± 54.74	18.59 ± 95.75
Withdrawal Escape Visit (4, 1, 0)	4.71 ± 133329.3	999 ± 999	0 ± 0
Safety Follow-up (92, 92, 98)	999 ± 999	0.52 ± 1158.85	0.14 ± 772.54

No statistical analyses for this end point

Secondary: Percentage of participants with positive anti-certolizumab pegol-antibody levels in plasma during the study

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End point title

Percentage of participants with positive anti-certolizumab pegol-antibody levels in plasma during the study

End point description

Treatment emergent ADAb status positive was defined as either baseline ADAb negative subjects having at least one ADAb confirmed positive sample post baseline or baseline ADAb positive subjects with at least one post baseline sample with >= minimum significant ratio (MSR) increase from baseline on CZP treatment. Once determined positive, the highest titer during Part A and Part B (including Escape and Safety Follow up) was used to categorize the subject. The primary purpose of the study was to evaluate treatment options for axSpA patients after being in sustained remission. Hence, one of the objectives was to evaluate the immunogenicity of these patients. The ADAb titer of the patients that did not reach sustained remission were therefore not analysed, and the Pharmacokinetic Set A as described in the protocol was removed from the SAP.

End point type

Secondary

End point timeframe

From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)

End point values	Placebo Double-Blind (PKSB)	Certolizumab pegol 200 mg Q2W Double-Blind (PKSB)	Certolizumab pegol 200 mg Q4W Double-Blind (PKSB)
Number of subjects analysed	101	102	105
Units: percentage of participants
number (not applicable)	100	96.1	100

No statistical analyses for this end point

Secondary: Percentage of participants with at least one Adverse Event (AE) during Part A of the study

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End point title

Percentage of participants with at least one Adverse Event (AE) during Part A of the study

End point description

An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

End point type

Secondary

End point timeframe

From Screening Period (Week -5 to Week -1) until Week 48

End point values	Certolizumab pegol Open-Label (SS) Wk 0-48
Number of subjects analysed	736
Units: percentage of participants
number (not applicable)
Screening Period (Week -5 to Week -1)	7.3
Open-Label Period (Week 0 to Week 48)	67.9

No statistical analyses for this end point

Secondary: Percentage of participants with at least one Adverse Event (AE) during Part B of the study

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End point title

Percentage of participants with at least one Adverse Event (AE) during Part B of the study

End point description

End point type

Secondary

End point timeframe

From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)

End point values	Placebo Double-Blind (SSB) Wk 48–96	Certolizumab pegol 200 mg Q2W Double-Blind (SSB) Wk 48–96	Certolizumab pegol 200 mg Q4W Double-Blind (SSB) Wk 48–96
Number of subjects analysed	103	104	105
Units: percentage of participants
number (not applicable)	54.4	57.7	61.0

No statistical analyses for this end point

Secondary: Percentage of participants with at least one Adverse Event (AE) and who experienced a flare during Part B of the study

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End point title

Percentage of participants with at least one Adverse Event (AE) and who experienced a flare during Part B of the study

End point description

End point type

Secondary

End point timeframe

From time of flare to Escape Week 12

End point values	Placebo DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12
Number of subjects analysed	72	6	15
Units: percentage of participants
number (not applicable)	51.4	83.3	46.7

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events were collected from Week 0 (Baseline) until the Safety Follow-Up Period (10 weeks after the last dose of study medication).

Adverse event reporting additional description

TEAEs counts are for each study period: Open-Label (Wk0-48), Double-Blind (Wk48-96) and Escape (Wk0-12). During Escape (last 3 columns) all participants received CZP 200 mg Q2W at time of TEAEs, although they were coming from 3 arms of the double-blind phase. Participants randomized or who entered escape but received no treatment are not included.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Certolizumab pegol Open-Label (SS) Wk 0-48

Reporting group description

Reporting group title

Placebo Double-Blind (SSB) Wk 48–96

Reporting group description

Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards. Participants formed the Safety Set Part B (SSB).

Reporting group title

Certolizumab pegol 200 mg Q2W Double-Blind (SSB) Wk 48–96

Reporting group description

Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards. Participants formed the SSB.

Reporting group title

Certolizumab pegol 200 mg Q4W Double-Blind (SSB) Wk 48–96

Reporting group description

Reporting group title

Placebo DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12

Reporting group description

Reporting group title

CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12

Reporting group description

Reporting group title

CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12

Reporting group description

Serious adverse events	Certolizumab pegol Open-Label (SS) Wk 0-48	Placebo Double-Blind (SSB) Wk 48–96	Certolizumab pegol 200 mg Q2W Double-Blind (SSB) Wk 48–96	Certolizumab pegol 200 mg Q4W Double-Blind (SSB) Wk 48–96	Placebo DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12
Total subjects affected by serious adverse events
subjects affected / exposed	44 / 736 (5.98%)	0 / 103 (0.00%)	5 / 104 (4.81%)	0 / 105 (0.00%)	0 / 72 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy on contraceptive
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Endometrial hyperplasia
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nasal septum deviation
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Schizophrenia
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
False positive tuberculosis test
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Meniscus injury
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epicondylitis
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ligament rupture
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Limb injury
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Tachycardia
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Migraine
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Optic neuritis
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Retinal vein occlusion
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Pancreatitis acute
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	1 / 104 (0.96%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis ulcerative
subjects affected / exposed	2 / 736 (0.27%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dental caries
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Glossitis
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Crohn's disease
subjects affected / exposed	0 / 736 (0.00%)	0 / 103 (0.00%)	1 / 104 (0.96%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	0 / 736 (0.00%)	0 / 103 (0.00%)	1 / 104 (0.96%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Irritable bowel syndrome
subjects affected / exposed	0 / 736 (0.00%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyshidrotic eczema
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pustular psoriasis
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urticaria
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Ureterolithiasis
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Axial spondyloarthritis
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	2 / 736 (0.27%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Perirectal abscess
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis aseptic
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulpitis dental
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis E
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abscess limb
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia mycoplasmal
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tuberculous pleurisy
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonsillar abscess
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 736 (0.00%)	0 / 103 (0.00%)	1 / 104 (0.96%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Latent tuberculosis
subjects affected / exposed	0 / 736 (0.00%)	0 / 103 (0.00%)	1 / 104 (0.96%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Certolizumab pegol Open-Label (SS) Wk 0-48	Placebo Double-Blind (SSB) Wk 48–96	Certolizumab pegol 200 mg Q2W Double-Blind (SSB) Wk 48–96	Certolizumab pegol 200 mg Q4W Double-Blind (SSB) Wk 48–96	Placebo DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12	CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12	CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12
Total subjects affected by non serious adverse events
subjects affected / exposed	188 / 736 (25.54%)	25 / 103 (24.27%)	31 / 104 (29.81%)	26 / 105 (24.76%)	20 / 72 (27.78%)	5 / 6 (83.33%)	7 / 15 (46.67%)
Investigations
Antinuclear antibody increased
subjects affected / exposed	0 / 736 (0.00%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Nervous system disorders
Cervicogenic vertigo
subjects affected / exposed	0 / 736 (0.00%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Sciatica
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)
occurrences all number	1	0	0	0	0	1	0
Blood and lymphatic system disorders
Iron deficiency anaemia
subjects affected / exposed	0 / 736 (0.00%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	1
General disorders and administration site conditions
Influenza like illness
subjects affected / exposed	8 / 736 (1.09%)	1 / 103 (0.97%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)
occurrences all number	9	1	0	0	0	1	0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	4 / 736 (0.54%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)
occurrences all number	4	0	0	0	0	2	0
Eye disorders
Iritis
subjects affected / exposed	0 / 736 (0.00%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	1
Gastrointestinal disorders
Irritable bowel syndrome
subjects affected / exposed	2 / 736 (0.27%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)
occurrences all number	2	0	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	12 / 736 (1.63%)	0 / 103 (0.00%)	3 / 104 (2.88%)	2 / 105 (1.90%)	0 / 72 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)
occurrences all number	14	0	3	2	0	0	1
Musculoskeletal and connective tissue disorders
Axial spondyloarthritis
subjects affected / exposed	8 / 736 (1.09%)	8 / 103 (7.77%)	6 / 104 (5.77%)	1 / 105 (0.95%)	0 / 72 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)
occurrences all number	8	8	6	1	0	0	0
Joint stiffness
subjects affected / exposed	0 / 736 (0.00%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	1
Infections and infestations
Nasopharyngitis
subjects affected / exposed	117 / 736 (15.90%)	8 / 103 (7.77%)	12 / 104 (11.54%)	13 / 105 (12.38%)	8 / 72 (11.11%)	2 / 6 (33.33%)	1 / 15 (6.67%)
occurrences all number	156	8	17	18	9	2	1
Upper respiratory tract infection
subjects affected / exposed	63 / 736 (8.56%)	10 / 103 (9.71%)	12 / 104 (11.54%)	11 / 105 (10.48%)	5 / 72 (6.94%)	1 / 6 (16.67%)	1 / 15 (6.67%)
occurrences all number	88	12	14	12	7	1	1
Pharyngitis
subjects affected / exposed	22 / 736 (2.99%)	3 / 103 (2.91%)	2 / 104 (1.92%)	6 / 105 (5.71%)	2 / 72 (2.78%)	0 / 6 (0.00%)	1 / 15 (6.67%)
occurrences all number	24	3	2	6	2	0	1
Oral herpes
subjects affected / exposed	13 / 736 (1.77%)	2 / 103 (1.94%)	1 / 104 (0.96%)	2 / 105 (1.90%)	1 / 72 (1.39%)	1 / 6 (16.67%)	0 / 15 (0.00%)
occurrences all number	21	3	3	2	1	3	0
Hordeolum
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)
occurrences all number	1	0	0	0	0	1	0
Influenza
subjects affected / exposed	9 / 736 (1.22%)	1 / 103 (0.97%)	3 / 104 (2.88%)	1 / 105 (0.95%)	2 / 72 (2.78%)	1 / 6 (16.67%)	0 / 15 (0.00%)
occurrences all number	9	1	3	1	3	1	0
Bronchitis
subjects affected / exposed	24 / 736 (3.26%)	3 / 103 (2.91%)	0 / 104 (0.00%)	3 / 105 (2.86%)	1 / 72 (1.39%)	0 / 6 (0.00%)	1 / 15 (6.67%)
occurrences all number	25	3	0	3	1	0	1
Conjunctivitis
subjects affected / exposed	6 / 736 (0.82%)	1 / 103 (0.97%)	0 / 104 (0.00%)	1 / 105 (0.95%)	0 / 72 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)
occurrences all number	6	1	0	1	0	0	1
Furuncle
subjects affected / exposed	1 / 736 (0.14%)	0 / 103 (0.00%)	0 / 104 (0.00%)	0 / 105 (0.00%)	0 / 72 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	0	0	0	0	1
Laryngitis
subjects affected / exposed	0 / 736 (0.00%)	0 / 103 (0.00%)	0 / 104 (0.00%)	1 / 105 (0.95%)	0 / 72 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	2	0	0	1
Latent tuberculosis
subjects affected / exposed	5 / 736 (0.68%)	0 / 103 (0.00%)	3 / 104 (2.88%)	2 / 105 (1.90%)	1 / 72 (1.39%)	0 / 6 (0.00%)	1 / 15 (6.67%)
occurrences all number	5	0	3	2	1	0	1
Sinusitis
subjects affected / exposed	12 / 736 (1.63%)	1 / 103 (0.97%)	0 / 104 (0.00%)	2 / 105 (1.90%)	0 / 72 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)
occurrences all number	12	1	0	2	0	0	1

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Were there any global substantial amendments to the protocol? Yes

24 Nov 2015

Global Protocol Amendment 1 (dated 24 Nov 2015) was a substantial protocol amendment implemented to include additional efficacy variables for study participants who entered Part A and Part B of the study, as well as a completely new list of other efficacy variables for those study participants who experienced a flare in Part B. For the purposes of analysis, 4 new analysis sets were defined, 2 of which were to be used in the pharmacokinetic (PK) analysis, 1 which was to be used in the efficacy analysis of study participants who experienced a flare in Part B, and 1 which was to be used to evaluate safety in study participants who ever received treatment with full-dose CZP during Part B of the study. Several clarifications were made including the time point for the assessment of the secondary efficacy variables for study participants who experienced a flare in Part B, human leukocyte antigen B27 (HLA-B27) as a Screening laboratory assessment, and the assessments to be performed 3 to 5 days prior to Week 48. Inconsistencies in the naming of Week 96 Visit and assessments were corrected, study personnel information was updated, and minor editorial changes were made.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants in Part B who did not experienced a flare

Primary: Percentage of participants in Part B who did not experienced a flare

Secondary: Percentage of participants achieving sustained remission at Week 48 in Part A

Secondary: Percentage of participants achieving sustained remission at Week 48 in Part A

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Week 48 in Part A

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Week 48 in Part A

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Week 48 in Part A

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Week 48 in Part A

Secondary: Time to flare in Part B

Secondary: Time to flare in Part B

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Week 96 in Part B

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Week 96 in Part B

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Week 96 in Part B

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Week 96 in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society 20 % response criteria (ASAS20) response at Week 96 in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society 20 % response criteria (ASAS20) response at Week 96 in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) response at Week 96 in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) response at Week 96 in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) 5/6 response criteria response at Week 96 in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) 5/6 response criteria response at Week 96 in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) partial remission (PR) response criteria response at Week 96 in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) partial remission (PR) response criteria response at Week 96 in Part B

Secondary: Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B

Secondary: Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B

Secondary: Percentage of participants with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response criteria response at Week 96 in Part B

Secondary: Percentage of participants with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response criteria response at Week 96 in Part B

Secondary: Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) score at Week 96 in Part B

Secondary: Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) score at Week 96 in Part B

Secondary: Change from Baseline in spine Ankylosing Spondylitis spine Magnetic Resonance Imaging Score for Disease activity (ASspIMRI-a) in the Berlin modification score at Week 96 in Part B

Secondary: Change from Baseline in spine Ankylosing Spondylitis spine Magnetic Resonance Imaging Score for Disease activity (ASspIMRI-a) in the Berlin modification score at Week 96 in Part B

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society 20 % response criteria (ASAS20) response at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society 20 % response criteria (ASAS20) response at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) response at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) response at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) 5/6 response criteria response at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) 5/6 response criteria response at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) partial remission (PR) response criteria response at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) partial remission (PR) response criteria response at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) score at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) score at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Change from Baseline in spine Ankylosing Spondylitis spine Magnetic Resonance Imaging Score for activity (ASspIMRI-a) in the Berlin modification score at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Change from Baseline in spine Ankylosing Spondylitis spine Magnetic Resonance Imaging Score for activity (ASspIMRI-a) in the Berlin modification score at Escape Week 12 for participants who experienced a flare in Part B

Secondary: Certolizumab pegol (CZP) Plasma Concentration during the study

Secondary: Certolizumab pegol (CZP) Plasma Concentration during the study

Secondary: Percentage of participants with positive anti-certolizumab pegol-antibody levels in plasma during the study

Secondary: Percentage of participants with positive anti-certolizumab pegol-antibody levels in plasma during the study

Secondary: Percentage of participants with at least one Adverse Event (AE) during Part A of the study

Secondary: Percentage of participants with at least one Adverse Event (AE) during Part A of the study

Secondary: Percentage of participants with at least one Adverse Event (AE) during Part B of the study

Secondary: Percentage of participants with at least one Adverse Event (AE) during Part B of the study

Secondary: Percentage of participants with at least one Adverse Event (AE) and who experienced a flare during Part B of the study

Secondary: Percentage of participants with at least one Adverse Event (AE) and who experienced a flare during Part B of the study

Adverse events