Trial Outcomes & Findings for Study to Assess the Short- and Long-term Efficacy of Certolizumab Pegol Plus Methotrexate Compared to Adalimumab Plus Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis (RA) Inadequately Responding to Methotrexate (NCT NCT01500278)

Last Updated: 2018-07-31

Results Overview

Subjects who met the ACR20 criteria were those subjects with at least 20% improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

915 participants

Primary outcome timeframe

Week 12

Results posted on

2018-07-31

Participant Flow

The study started to enroll patients in December 2011 and concluded in January 2016.

Participant Flow refers to the Randomized Treatment Group (RTG) that consisted of all subjects randomized into the study.

Participant milestones

Participant milestones
Measure	CZP+MTX (RTG) Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10. Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	ADA+MTX (RTG) Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4. Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.
Week 0 - Week 12 STARTED	457	458
Week 0 - Week 12 COMPLETED	426	428
Week 0 - Week 12 NOT COMPLETED	31	30
Week 13 - Week 104 STARTED	426	428
Week 13 - Week 104 COMPLETED	287	302
Week 13 - Week 104 NOT COMPLETED	139	126

Reasons for withdrawal

Reasons for withdrawal
Measure	CZP+MTX (RTG) Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10. Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	ADA+MTX (RTG) Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4. Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.
Week 0 - Week 12 Lack of Efficacy	0	1
Week 0 - Week 12 Protocol Violation	10	16
Week 0 - Week 12 Lost to Follow-up	1	1
Week 0 - Week 12 Withdrawal by Subject	7	2
Week 0 - Week 12 Protocol violation on screening X-ray	1	0
Week 0 - Week 12 Patient decision	1	0
Week 0 - Week 12 Exclusion criteria not met	1	0
Week 0 - Week 12 Investigator decision	1	0
Week 0 - Week 12 Prior history of serious disease	1	0
Week 0 - Week 12 Sponsor decision	1	0
Week 0 - Week 12 Personal reason	0	1
Week 0 - Week 12 Other serious disease	0	1
Week 0 - Week 12 Adverse event (AE), not fatal	7	8
Week 13 - Week 104 Lack of Efficacy	11	12
Week 13 - Week 104 Protocol Violation	6	6
Week 13 - Week 104 Lost to Follow-up	6	5
Week 13 - Week 104 Withdrawal by Subject	22	13
Week 13 - Week 104 Week 24 Non-Responder	20	16
Week 13 - Week 104 Non/bad compliance	7	5
Week 13 - Week 104 Recurrent infections	1	0
Week 13 - Week 104 False positive test	1	2
Week 13 - Week 104 Sponsor request	4	0
Week 13 - Week 104 Withdrawn in error	1	0
Week 13 - Week 104 Exclusion criteria not met	1	0
Week 13 - Week 104 Protocol deviation	1	0
Week 13 - Week 104 Principal investigator retiring	1	0
Week 13 - Week 104 Patient declined Safety Follow Up Visit	1	0
Week 13 - Week 104 Abnormal questionable chest X-ray	0	2
Week 13 - Week 104 Relocation	0	1
Week 13 - Week 104 Sponsor decision	0	2
Week 13 - Week 104 Medical monitor decision	0	2
Week 13 - Week 104 Personal reason	0	1
Week 13 - Week 104 Not completed	0	1
Week 13 - Week 104 Death	2	4
Week 13 - Week 104 Adverse Event	54	54

Baseline Characteristics

Study to Assess the Short- and Long-term Efficacy of Certolizumab Pegol Plus Methotrexate Compared to Adalimumab Plus Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis (RA) Inadequately Responding to Methotrexate

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CZP+MTX (RTG) n=457 Participants Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10. Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	ADA+MTX (RTG) n=458 Participants Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4. Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	Total Title n=915 Participants
Age, Categorical <=18 years	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	364 Participants n=93 Participants	372 Participants n=4 Participants	736 Participants n=27 Participants
Age, Categorical >=65 years	93 Participants n=93 Participants	85 Participants n=4 Participants	178 Participants n=27 Participants
Age, Continuous Arithmetic mean (standard deviation)	53.5 years STANDARD_DEVIATION 12.3 • n=93 Participants	52.9 years STANDARD_DEVIATION 12.8 • n=4 Participants	53.2 years STANDARD_DEVIATION 12.5 • n=27 Participants
Sex: Female, Male Female	360 Participants n=93 Participants	363 Participants n=4 Participants	723 Participants n=27 Participants
Sex: Female, Male Male	97 Participants n=93 Participants	95 Participants n=4 Participants	192 Participants n=27 Participants

PRIMARY outcome

Timeframe: Week 12

Population: The Full Analysis Set (FAS) consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement.

Outcome measures

Outcome measures
Measure	CZP+MTX (FAS) n=454 Participants Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10. Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	ADA+MTX (FAS) n=454 Participants Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4. Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.
Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12	69.2 Percentage of subjects	71.4 Percentage of subjects

PRIMARY outcome

Timeframe: Week 104

Population: The Full Analysis Set (FAS) consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement.

DAS28 \[ESR\] was calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC), Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √ (TJC) + 0.28 x √ (SJC) + 0.70 x lognat (ESR) + 0.014 x Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.

Outcome measures

Outcome measures
Measure	CZP+MTX (FAS) n=454 Participants Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10. Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	ADA+MTX (FAS) n=454 Participants Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4. Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104	35.5 Percentage of subjects	33.5 Percentage of subjects

SECONDARY outcome

Timeframe: Week 104

Population: Week 12 Responders were defined as those with DAS28(ESR) LDA (defined as DAS28\[ESR\] ≤3.2) or a DAS28(ESR) CFB reduction of ≥1.2 at Week 12.

Outcome measures

Outcome measures
Measure	CZP+MTX (FAS) n=353 Participants Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10. Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	ADA+MTX (FAS) n=361 Participants Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4. Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.
Percentage of Week 12 Responders Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104	45.6 Percentage of subjects	42.4 Percentage of subjects

SECONDARY outcome

Timeframe: Week 6

Population: The Full Analysis Set (FAS) consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement.

Outcome measures

Outcome measures
Measure	CZP+MTX (FAS) n=454 Participants Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10. Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	ADA+MTX (FAS) n=454 Participants Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4. Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.
Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 6	64.5 Percentage of subjects	60.8 Percentage of subjects

SECONDARY outcome

Timeframe: Week 6

Population: The Full Analysis Set (FAS) consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement.

Outcome measures

Outcome measures
Measure	CZP+MTX (FAS) n=454 Participants Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10. Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	ADA+MTX (FAS) n=454 Participants Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4. Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 6	20.5 Percentage of subjects	18.1 Percentage of subjects

SECONDARY outcome

Timeframe: Week 12

Population: The Full Analysis Set (FAS) consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement.

Outcome measures

Outcome measures
Measure	CZP+MTX (FAS) n=454 Participants Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10. Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	ADA+MTX (FAS) n=454 Participants Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4. Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12	30.4 Percentage of subjects	29.7 Percentage of subjects

SECONDARY outcome

Timeframe: Week 104

Population: Week 12 Responders were defined as those with DAS28(ESR) LDA (defined as DAS28\[ESR\] ≤3.2) or a DAS28(ESR) CFB reduction of ≥1.2 at Week 12. Only subjects responding at both Week 6 and Week 12 are included in this analysis.

Outcome measures

Outcome measures
Measure	CZP+MTX (FAS) n=310 Participants Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10. Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	ADA+MTX (FAS) n=298 Participants Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4. Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.
Percentage of Subjects With a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104, in Subjects Responding at Both Week 6 and Week 12	47.7 Percentage of subjects	46.6 Percentage of subjects

SECONDARY outcome

Timeframe: From Baseline to Week 104

Population: The Full Analysis Set (FAS) consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement.

HAQ-DI was derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question was scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do), and the total HAQ-DI was scored on the scale of 0-3 as well. Change from Baseline was computed as the value at Week 104 minus the Baseline value. A negative value in Change from Baseline indicates an improvement.

Outcome measures

Outcome measures
Measure	CZP+MTX (FAS) n=454 Participants Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10. Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	ADA+MTX (FAS) n=454 Participants Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4. Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 104	-0.62 Units on a Scale Standard Error 0.03	-0.72 Units on a Scale Standard Error 0.03

SECONDARY outcome

Timeframe: From Week 12 up to Week 104

Population: Week 12 Responders were defined as those with DAS28(ESR) LDA (defined as DAS28\[ESR\] ≤3.2) or a DAS28(ESR) CFB reduction of ≥1.2 at Week 12.

Response at Week 12 means that a subject had either a Disease Activity Score 28 \[Erythrocyte Sedimentation Rate\] (DAS28 \[ESR\]) ≤ 3.2 at Week 12 or had a reduction of DAS28 \[ESR\] ≥ 1.2 from Baseline to Week 12. Kaplan-Meier Estimates of Proportion of Subjects Discontinued are presented per study week (days relative to Week 12 visit).

Outcome measures

Outcome measures
Measure	CZP+MTX (FAS) n=353 Participants Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10. Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.	ADA+MTX (FAS) n=361 Participants Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4. Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102. Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period. All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously.
Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 Week 13 (Day 7)	0 proportion of subjects	0.0028 proportion of subjects
Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 Week 26 (Day 98)	0.0198 proportion of subjects	0.0332 proportion of subjects
Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 Week 39 (Day 189)	0.0453 proportion of subjects	0.0609 proportion of subjects
Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 Week 52 (Day 280)	0.0963 proportion of subjects	0.0886 proportion of subjects
Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 Week 65 (Day 371)	0.1643 proportion of subjects	0.1607 proportion of subjects
Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 Week 78 (Day 462)	0.2181 proportion of subjects	0.1967 proportion of subjects
Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 Week 91 (Day 553)	0.2408 proportion of subjects	0.2105 proportion of subjects
Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 Week 104 (Day 644)	0.2635 proportion of subjects	0.2247 proportion of subjects

Adverse Events

CZP+MTX (SS)

Serious events: 67 serious events

Other events: 269 other events

Deaths: 0 deaths

ADA+MTX (SS)

Serious events: 58 serious events

Other events: 244 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	CZP+MTX (SS) n=516 participants at risk All subjects who received at least 1 dose of Certolizumab pegol (CZP). All adverse events that occurred when the subject was receiving CZP treatment are summarized in this group.	ADA+MTX (SS) n=523 participants at risk All subjects who received at least 1 dose of Adalimumab (ADA). All adverse events that occurred when the subject was receiving ADA treatment are summarized in this group.
Gastrointestinal disorders Diarrhoea	6.0% 31/516 • Number of events 36 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.	4.4% 23/523 • Number of events 26 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.
Infections and infestations Nasopharyngitis	15.3% 79/516 • Number of events 116 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.	12.8% 67/523 • Number of events 106 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.
Infections and infestations Upper respiratory tract infection	10.3% 53/516 • Number of events 74 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.	11.5% 60/523 • Number of events 80 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.
Infections and infestations Urinary tract infection	8.3% 43/516 • Number of events 58 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.	9.8% 51/523 • Number of events 65 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.
Infections and infestations Latent tuberculosis	6.0% 31/516 • Number of events 31 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.	5.2% 27/523 • Number of events 27 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.
Infections and infestations Sinusitis	6.0% 31/516 • Number of events 35 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.	4.0% 21/523 • Number of events 31 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.
Infections and infestations Bronchitis	5.6% 29/516 • Number of events 33 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.	4.8% 25/523 • Number of events 26 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.
Nervous system disorders Headache	10.7% 55/516 • Number of events 62 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.	9.0% 47/523 • Number of events 77 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.
Respiratory, thoracic and mediastinal disorders Cough	4.1% 21/516 • Number of events 26 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.	5.4% 28/523 • Number of events 35 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.
Vascular disorders Hypertension	7.2% 37/516 • Number of events 42 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.	5.9% 31/523 • Number of events 34 • During the entire study period (From Week -4 to Week 104). The AEs of subjects who switched study treatment at Week 12 (W12) were presented under the original treatment group if they occurred after the 1st administration of study treatment (W0) until the day before W12 treatment administration, and were presented under the switched treatment group if they occurred after the W12 treatment administration up to and including 70 days after the last injection. Subjects who switched treatment at W12 were included in both CZP+MTX(SS) and ADA+MTX(SS) group.

Additional Information

UCB

Cares

Phone: +1877 822

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60