Trial Outcomes & Findings for Efficacy at 24 Weeks and Safety, Tolerability and Long Term Efficacy of Secukinumab (AIN457) in Patients With Active Rheumatoid Arthritis (RA) and an Inadequate Response to Anti-Tumor Necrosis Factor α (Anti-TNFα) Agents (CAIN457F2309 and CAIN457F2309E1) (NCT NCT01350804)

NCT ID: NCT01350804

Last Updated: 2016-05-23

Results Overview

ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire \[HAQ-DI\] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). The ACR20 response results at week 24 used non-responder imputation.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 551 participants
• Primary outcome timeframe: week 24
• Results posted on: 2016-05-23

Participant Flow

At baseline, participants were randomized to 1 of 4 treatment groups. Placebo non-responders at week16 were re-randomized to receive AIN457 75mg or AIN457 150mg. Placebo responders at Week16 were re-randomized to receive AIN457 75mg or AIN457 150mg at Week24. Fifteen participants from the placebo group discontinued prior to re-randomization.

Abatacept responders at Week16 continued on abatacept and non-responders at Week 16 were re-randomized to begin either AIN457 75mg or AIN457 150mg at Week 24. Of the 551 core study participants, 254 participants entered the extension study.

Participant milestones

Measure	AIN457 10mg/kg - 75 mg Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Core Study STARTED	138	137	138	138
Core Study Safety Set	137	136	139	137
Core Study Tratment Switch to AIN457 at Week 16	0	0	78	0
Core Study Treatment Switch to AIN457 at Week 24	0	0	45	37
Core Study Full Analysis Set	138	137	138	138
Core Study COMPLETED	97	90	91	112
Core Study NOT COMPLETED	41	47	47	26
Extension Study, Weeks 52 - 260 STARTED	80	79	72	23
Extension Study, Weeks 52 - 260 COMPLETED	0	0	0	0
Extension Study, Weeks 52 - 260 NOT COMPLETED	80	79	72	23

Reasons for withdrawal

Measure	AIN457 10mg/kg - 75 mg Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Core Study Withdrawal by Subject	11	17	16	7
Core Study Study terminated by Sponsor	0	0	0	2
Core Study Protocol deviation	1	0	1	0
Core Study Physician Decision	1	0	1	3
Core Study Lost to Follow-up	3	0	2	1
Core Study Lack of Efficacy	16	19	18	5
Core Study Death	1	1	1	0
Core Study Adverse Event	8	10	8	8
Extension Study, Weeks 52 - 260 Withdrawal by Subject	5	6	4	3
Extension Study, Weeks 52 - 260 Study terminated by Sponsor	67	67	64	16
Extension Study, Weeks 52 - 260 Physician Decision	1	0	2	0
Extension Study, Weeks 52 - 260 Lost to Follow-up	0	1	0	0
Extension Study, Weeks 52 - 260 Lack of Efficacy	4	4	0	1
Extension Study, Weeks 52 - 260 Adverse Event	3	1	2	3

Baseline Characteristics

Efficacy at 24 Weeks and Safety, Tolerability and Long Term Efficacy of Secukinumab (AIN457) in Patients With Active Rheumatoid Arthritis (RA) and an Inadequate Response to Anti-Tumor Necrosis Factor α (Anti-TNFα) Agents (CAIN457F2309 and CAIN457F2309E1)

Baseline characteristics by cohort

Measure	AIN457 10mg/kg - 75 mg n=138 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=137 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=138 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=138 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Total n=551 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	111 Participants n=5 Participants	103 Participants n=7 Participants	106 Participants n=5 Participants	115 Participants n=4 Participants	435 Participants n=21 Participants
Age, Categorical >=65 years	27 Participants n=5 Participants	34 Participants n=7 Participants	32 Participants n=5 Participants	23 Participants n=4 Participants	116 Participants n=21 Participants
Sex: Female, Male Female	119 Participants n=5 Participants	109 Participants n=7 Participants	115 Participants n=5 Participants	107 Participants n=4 Participants	450 Participants n=21 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	28 Participants n=7 Participants	23 Participants n=5 Participants	31 Participants n=4 Participants	101 Participants n=21 Participants

PRIMARY outcome

Timeframe: week 24

Population: Full analysis set: the full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.

ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). The ACR20 response results at week 24 used non-responder imputation.

Outcome measures

Measure	Placebo Responder - AIN457 150mg Participants switched from placebo to AIN457 150 mg starting at week 24.	Abatacept Responders Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).	Abatacept Non-responders - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.	Abatacept Non-responders - AIN457 150mg Participants switched from abatacept to AIN457 150 mg starting at week 24.	AIN457 10mg/kg - 75 mg n=138 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=137 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=138 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=138 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Placebo Non-responder - AIN457 75 mg Participants switched from placebo to AIN457 75 mg starting at week 16.	Placebo Non-responder - AIN457 150 mg Participants switched from placebo to AIN457 150 mg starting at week 16.	Placebo Responder - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.
Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20).	—	—	—	—	28.3 Percentage of participants	30.7 Percentage of participants	18.1 Percentage of participants	42.8 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: baseline, week 24

Population: Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and week 24 were analyzed. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.

The DAS28 is a measure of disease activity in RA based on Swollen and Tender Joint Counts (out of a total of 28), hsCRP and the Patient's Global Assessment of Disease Activity. A DAS28 score greater than 5.1 implies active disease, equal to or less than 3.2 low disease activity, and less than 2.6 remission. A negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo Responder - AIN457 150mg Participants switched from placebo to AIN457 150 mg starting at week 24.	Abatacept Responders Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).	Abatacept Non-responders - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.	Abatacept Non-responders - AIN457 150mg Participants switched from abatacept to AIN457 150 mg starting at week 24.	AIN457 10mg/kg - 75 mg n=116 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=108 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=44 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=84 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Placebo Non-responder - AIN457 75 mg Participants switched from placebo to AIN457 75 mg starting at week 16.	Placebo Non-responder - AIN457 150 mg Participants switched from placebo to AIN457 150 mg starting at week 16.	Placebo Responder - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP)	—	—	—	—	-1.47 score on a scale Standard Error 0.115	-1.47 score on a scale Standard Error 0.119	-1.02 score on a scale Standard Error 0.163	-2.07 score on a scale Standard Error 0.128	—	—	—

SECONDARY outcome

Timeframe: baseline, week 24

Population: Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and week 24 were analyzed. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.

The HAQ-DI assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo Responder - AIN457 150mg Participants switched from placebo to AIN457 150 mg starting at week 24.	Abatacept Responders Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).	Abatacept Non-responders - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.	Abatacept Non-responders - AIN457 150mg Participants switched from abatacept to AIN457 150 mg starting at week 24.	AIN457 10mg/kg - 75 mg n=117 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=110 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=44 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=86 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Placebo Non-responder - AIN457 75 mg Participants switched from placebo to AIN457 75 mg starting at week 16.	Placebo Non-responder - AIN457 150 mg Participants switched from placebo to AIN457 150 mg starting at week 16.	Placebo Responder - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.
Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)	—	—	—	—	-0.30 score on a scale Standard Error 0.049	-0.39 score on a scale Standard Error 0.051	-0.26 score on a scale Standard Error 0.065	-0.61 score on a scale Standard Error 0.053	—	—	—

SECONDARY outcome

Timeframe: week 24

Population: Full analysis set: the full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.

ACR50 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 50% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). The ACR50 response results at week 24 used non-responder imputation.

Outcome measures

Measure	Placebo Responder - AIN457 150mg Participants switched from placebo to AIN457 150 mg starting at week 24.	Abatacept Responders Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).	Abatacept Non-responders - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.	Abatacept Non-responders - AIN457 150mg Participants switched from abatacept to AIN457 150 mg starting at week 24.	AIN457 10mg/kg - 75 mg n=138 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=137 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=138 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=138 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Placebo Non-responder - AIN457 75 mg Participants switched from placebo to AIN457 75 mg starting at week 16.	Placebo Non-responder - AIN457 150 mg Participants switched from placebo to AIN457 150 mg starting at week 16.	Placebo Responder - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.
Percentage of Participants Achieving ACR50	—	—	—	—	11.6 Percentage of participants	16.8 Percentage of participants	9.4 Percentage of participants	27.5 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24

Population: Participants from the full analysis set were considered for the analysis. Participants with missing data were considered non-responders at the respective time point. Placebo and Abatacept participants were considered non-responders from the time of treatment switch.

ACR20, ACR 50 and ACR 70 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20%, 50% and/or 70% improvement, respectively, in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).

Outcome measures

Measure	Placebo Responder - AIN457 150mg Participants switched from placebo to AIN457 150 mg starting at week 24.	Abatacept Responders Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).	Abatacept Non-responders - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.	Abatacept Non-responders - AIN457 150mg Participants switched from abatacept to AIN457 150 mg starting at week 24.	AIN457 10mg/kg - 75 mg n=138 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=137 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=138 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=138 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Placebo Non-responder - AIN457 75 mg Participants switched from placebo to AIN457 75 mg starting at week 16.	Placebo Non-responder - AIN457 150 mg Participants switched from placebo to AIN457 150 mg starting at week 16.	Placebo Responder - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR70, week 16	—	—	—	—	5.1 Percentage of participants	8.0 Percentage of participants	2.9 Percentage of participants	9.4 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR70, week 20	—	—	—	—	4.3 Percentage of participants	7.3 Percentage of participants	5.8 Percentage of participants	10.1 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR70, week 24	—	—	—	—	5.1 Percentage of participants	10.2 Percentage of participants	5.1 Percentage of participants	12.3 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR20, week 1	—	—	—	—	21.0 Percentage of participants	17.5 Percentage of participants	7.2 Percentage of participants	10.9 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR20, week 2	—	—	—	—	24.6 Percentage of participants	21.2 Percentage of participants	12.3 Percentage of participants	23.9 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR20, week 4	—	—	—	—	34.1 Percentage of participants	27.0 Percentage of participants	21.7 Percentage of participants	31.2 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR20, week 8	—	—	—	—	35.5 Percentage of participants	41.6 Percentage of participants	21.0 Percentage of participants	49.3 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR20, week 12	—	—	—	—	28.3 Percentage of participants	33.6 Percentage of participants	24.6 Percentage of participants	47.1 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR20, week 16	—	—	—	—	34.1 Percentage of participants	39.4 Percentage of participants	23.2 Percentage of participants	51.4 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR20, week 20	—	—	—	—	26.8 Percentage of participants	38.0 Percentage of participants	18.1 Percentage of participants	47.8 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR20, week 24	—	—	—	—	28.3 Percentage of participants	30.7 Percentage of participants	18.1 Percentage of participants	42.8 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR50, week 1	—	—	—	—	6.5 Percentage of participants	2.9 Percentage of participants	0.7 Percentage of participants	1.4 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR50, week 2	—	—	—	—	5.1 Percentage of participants	8.8 Percentage of participants	2.9 Percentage of participants	2.9 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR50, week 4	—	—	—	—	9.4 Percentage of participants	10.2 Percentage of participants	2.9 Percentage of participants	7.2 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR50, week 8	—	—	—	—	7.2 Percentage of participants	15.3 Percentage of participants	10.1 Percentage of participants	18.8 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR50, week 12	—	—	—	—	8.7 Percentage of participants	13.1 Percentage of participants	10.1 Percentage of participants	22.5 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR50, week 16	—	—	—	—	13.8 Percentage of participants	20.4 Percentage of participants	9.4 Percentage of participants	23.9 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR50, week 20	—	—	—	—	12.3 Percentage of participants	18.2 Percentage of participants	8.0 Percentage of participants	26.8 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR50, week 24	—	—	—	—	11.6 Percentage of participants	16.8 Percentage of participants	9.4 Percentage of participants	27.5 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR70, week 1	—	—	—	—	0.7 Percentage of participants	0.7 Percentage of participants	0.0 Percentage of participants	0.7 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR70, week 2	—	—	—	—	1.4 Percentage of participants	0.7 Percentage of participants	1.4 Percentage of participants	0.7 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR70, week 4	—	—	—	—	4.3 Percentage of participants	2.9 Percentage of participants	1.4 Percentage of participants	1.4 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR70, week 8	—	—	—	—	1.4 Percentage of participants	4.4 Percentage of participants	2.9 Percentage of participants	5.8 Percentage of participants	—	—	—
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation ACR70, week 12	—	—	—	—	2.2 Percentage of participants	2.9 Percentage of participants	2.9 Percentage of participants	9.4 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Population: Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and each post-baseline time point were analyzed for that post-baseline time point. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.

ACR20, ACR 50 and ACR 70 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20%, 50% and/or 70% improvement, respectively, in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). The ACR20, ACR50 and ACR70 response results from baseline up to week 52 were based on observed data, i.e. without imputation.

Outcome measures

Measure	Placebo Responder - AIN457 150mg n=22 Participants Participants switched from placebo to AIN457 150 mg starting at week 24.	Abatacept Responders n=101 Participants Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).	Abatacept Non-responders - AIN457 75mg n=18 Participants Participants switched from placebo to AIN457 75 mg starting at week 24.	Abatacept Non-responders - AIN457 150mg n=19 Participants Participants switched from abatacept to AIN457 150 mg starting at week 24.	AIN457 10mg/kg - 75 mg n=138 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=137 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=138 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=138 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Placebo Non-responder - AIN457 75 mg n=39 Participants Participants switched from placebo to AIN457 75 mg starting at week 16.	Placebo Non-responder - AIN457 150 mg n=39 Participants Participants switched from placebo to AIN457 150 mg starting at week 16.	Placebo Responder - AIN457 75mg n=23 Participants Participants switched from placebo to AIN457 75 mg starting at week 24.
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk28,n=115,103,na,na,33,35,21,21,86,17,19	90.5 Percentage of participants	74.4 Percentage of participants	41.2 Percentage of participants	42.1 Percentage of participants	47.8 Percentage of participants	65.0 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	33.3 Percentage of participants	37.1 Percentage of participants	71.4 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk48,n=94,89,na,na,28,26,18,19,77,12,14	10.5 Percentage of participants	27.3 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	9.6 Percentage of participants	20.2 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	3.6 Percentage of participants	15.4 Percentage of participants	33.3 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk 1,n=132,129,130,130,39,35,21,22,96,17,17	13.6 Percentage of participants	14.6 Percentage of participants	0.0 Percentage of participants	5.9 Percentage of participants	22.7 Percentage of participants	18.6 Percentage of participants	7.7 Percentage of participants	11.5 Percentage of participants	5.1 Percentage of participants	5.7 Percentage of participants	14.3 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk 2,n=131,130,134,134,39,36,23,22,99,17,18	13.6 Percentage of participants	29.3 Percentage of participants	11.8 Percentage of participants	16.7 Percentage of participants	26.7 Percentage of participants	22.3 Percentage of participants	12.7 Percentage of participants	25.4 Percentage of participants	2.6 Percentage of participants	11.1 Percentage of participants	34.8 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk 4,n=133,132,131,129,39,39,23,21,93,17,19	42.9 Percentage of participants	41.9 Percentage of participants	17.6 Percentage of participants	10.5 Percentage of participants	36.1 Percentage of participants	28.0 Percentage of participants	22.9 Percentage of participants	34.1 Percentage of participants	15.4 Percentage of participants	12.8 Percentage of participants	43.5 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk 8,n=132,127,131,131,39,39,23,22,95,17,19	31.8 Percentage of participants	61.1 Percentage of participants	29.4 Percentage of participants	31.6 Percentage of participants	38.6 Percentage of participants	44.9 Percentage of participants	22.1 Percentage of participants	52.7 Percentage of participants	17.9 Percentage of participants	12.8 Percentage of participants	39.1 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk 12,n=130,115,123,129,39,37,23,21,94,17,18	52.4 Percentage of participants	62.8 Percentage of participants	17.6 Percentage of participants	22.2 Percentage of participants	30.8 Percentage of participants	40.0 Percentage of participants	27.6 Percentage of participants	51.2 Percentage of participants	15.4 Percentage of participants	16.2 Percentage of participants	47.8 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk 16,n=126,118,116,129,36,37,21,22,94,16,19	63.6 Percentage of participants	76.6 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	38.1 Percentage of participants	45.8 Percentage of participants	27.6 Percentage of participants	55.8 Percentage of participants	2.8 Percentage of participants	2.7 Percentage of participants	76.2 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk 20,n=122,114,119,126,38,37,23,21,91,16,19	47.6 Percentage of participants	73.6 Percentage of participants	6.3 Percentage of participants	26.3 Percentage of participants	39.3 Percentage of participants	51.8 Percentage of participants	42.9 Percentage of participants	57.9 Percentage of participants	42.1 Percentage of participants	29.7 Percentage of participants	60.9 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk 24,n=117,110,117,121,38,36,21,22,87,16,18	59.1 Percentage of participants	69.0 Percentage of participants	31.3 Percentage of participants	27.8 Percentage of participants	45.3 Percentage of participants	48.2 Percentage of participants	40.2 Percentage of participants	57.9 Percentage of participants	26.3 Percentage of participants	33.3 Percentage of participants	57.1 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk32,n=104,97,na,na,33,30,21,19,87,17,17	68.4 Percentage of participants	74.7 Percentage of participants	23.5 Percentage of participants	47.1 Percentage of participants	56.7 Percentage of participants	61.9 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	51.5 Percentage of participants	36.7 Percentage of participants	81.0 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk36,n=102,93,na,na,30,30,21,20,85,18,16	65.0 Percentage of participants	77.6 Percentage of participants	27.8 Percentage of participants	56.3 Percentage of participants	56.9 Percentage of participants	53.8 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	46.7 Percentage of participants	56.7 Percentage of participants	85.7 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk40,n=96,90,na,na,28,28,21,19,85,15,17	73.7 Percentage of participants	71.8 Percentage of participants	40.0 Percentage of participants	58.8 Percentage of participants	53.1 Percentage of participants	61.1 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	53.6 Percentage of participants	53.6 Percentage of participants	85.7 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk4,n=133,132,131,129,39,39,23,21,93,17,19	9.5 Percentage of participants	10.8 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	9.8 Percentage of participants	10.6 Percentage of participants	3.1 Percentage of participants	7.8 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	8.7 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk44,n=97,90,na,na,28,27,20,18,84,15,16	77.8 Percentage of participants	77.4 Percentage of participants	33.3 Percentage of participants	31.3 Percentage of participants	56.7 Percentage of participants	61.1 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	50.0 Percentage of participants	55.6 Percentage of participants	85.0 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk48,n=94,89,na,na,28,26,18,19,77,12,14	57.9 Percentage of participants	71.4 Percentage of participants	25.0 Percentage of participants	50.0 Percentage of participants	57.4 Percentage of participants	68.5 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	53.6 Percentage of participants	61.5 Percentage of participants	72.2 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR20,wk52,n=92,88,na,na,28,26,20,18,79,15,15	88.9 Percentage of participants	74.7 Percentage of participants	40.0 Percentage of participants	33.3 Percentage of participants	56.5 Percentage of participants	62.5 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	39.3 Percentage of participants	57.7 Percentage of participants	75.0 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk1,n=132,129,130,130,39,35,21,22,96,17,17	0.0 Percentage of participants	1.0 Percentage of participants	0.0 Percentage of participants	5.9 Percentage of participants	6.8 Percentage of participants	3.1 Percentage of participants	0.8 Percentage of participants	1.5 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	4.8 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk2,n=131,130,134,134,39,36,23,22,99,17,18	4.5 Percentage of participants	3.0 Percentage of participants	0.0 Percentage of participants	5.6 Percentage of participants	5.3 Percentage of participants	9.2 Percentage of participants	3.0 Percentage of participants	3.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	13.0 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk8,n=132,127,131,131,39,39,23,22,95,17,19	9.1 Percentage of participants	25.3 Percentage of participants	11.8 Percentage of participants	5.3 Percentage of participants	9.1 Percentage of participants	16.5 Percentage of participants	10.7 Percentage of participants	20.6 Percentage of participants	5.1 Percentage of participants	5.1 Percentage of participants	34.8 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk12,n=130,115,123,129,39,37,23,21,94,17,18	23.8 Percentage of participants	30.9 Percentage of participants	5.9 Percentage of participants	11.1 Percentage of participants	10.0 Percentage of participants	15.7 Percentage of participants	11.4 Percentage of participants	24.8 Percentage of participants	2.6 Percentage of participants	8.1 Percentage of participants	21.7 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk16,n=126,118,116,129,36,37,21,22,94,16,19	22.7 Percentage of participants	36.2 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	15.9 Percentage of participants	23.7 Percentage of participants	11.2 Percentage of participants	26.4 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	38.1 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk20,n=122,114,119,126,38,37,23,21,91,16,19	14.3 Percentage of participants	40.7 Percentage of participants	0.0 Percentage of participants	15.8 Percentage of participants	15.6 Percentage of participants	21.9 Percentage of participants	12.6 Percentage of participants	31.7 Percentage of participants	7.9 Percentage of participants	2.7 Percentage of participants	34.8 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk24,n=117,110,117,121,38,36,21,22,87,16,18	22.7 Percentage of participants	44.8 Percentage of participants	0.0 Percentage of participants	5.6 Percentage of participants	14.5 Percentage of participants	22.7 Percentage of participants	14.5 Percentage of participants	33.1 Percentage of participants	0.0 Percentage of participants	11.1 Percentage of participants	38.1 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk28,n=115,103,na,na,33,35,21,21,86,17,19	33.3 Percentage of participants	41.9 Percentage of participants	23.5 Percentage of participants	0.0 Percentage of participants	13.9 Percentage of participants	31.1 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	6.1 Percentage of participants	8.6 Percentage of participants	33.3 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk32,n=104,97,na,na,33,30,21,19,87,17,17	31.6 Percentage of participants	47.1 Percentage of participants	5.9 Percentage of participants	0.0 Percentage of participants	21.2 Percentage of participants	32.0 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	6.1 Percentage of participants	13.3 Percentage of participants	42.9 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk36,n=102,93,na,na,30,30,21,20,85,18,16	20.0 Percentage of participants	47.1 Percentage of participants	16.7 Percentage of participants	18.8 Percentage of participants	23.5 Percentage of participants	24.7 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	16.7 Percentage of participants	16.7 Percentage of participants	28.6 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk40,n=96,90,na,na,28,28,21,19,85,15,17	26.3 Percentage of participants	45.9 Percentage of participants	20.0 Percentage of participants	5.9 Percentage of participants	25.0 Percentage of participants	25.6 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	14.3 Percentage of participants	28.6 Percentage of participants	38.1 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk44,n=97,90,na,na,28,27,20,18,84,15,16	33.3 Percentage of participants	50.0 Percentage of participants	13.3 Percentage of participants	6.3 Percentage of participants	27.8 Percentage of participants	30.0 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	7.1 Percentage of participants	29.6 Percentage of participants	35.0 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk48,n=94,89,na,na,28,26,18,19,77,12,14	26.3 Percentage of participants	48.1 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	25.5 Percentage of participants	42.7 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	14.3 Percentage of participants	23.1 Percentage of participants	38.9 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR50,wk52,n=92,88,na,na,28,26,20,18,79,15,15	44.4 Percentage of participants	51.9 Percentage of participants	20.0 Percentage of participants	13.3 Percentage of participants	26.1 Percentage of participants	45.5 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	10.7 Percentage of participants	26.9 Percentage of participants	40.0 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk1,n=132,129,130,130,39,35,21,22,96,17,17	0.0 Percentage of participants	1.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.8 Percentage of participants	0.8 Percentage of participants	0.0 Percentage of participants	0.8 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk2,n=131,130,134,134,39,36,23,22,99,17,18	4.5 Percentage of participants	1.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	1.5 Percentage of participants	0.8 Percentage of participants	1.5 Percentage of participants	0.7 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	4.3 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk4,n=133,132,131,129,39,39,23,21,93,17,19	4.8 Percentage of participants	2.2 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	4.5 Percentage of participants	3.0 Percentage of participants	1.5 Percentage of participants	1.6 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	4.3 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk8,n=132,127,131,131,39,39,23,22,95,17,19	0.0 Percentage of participants	7.4 Percentage of participants	5.9 Percentage of participants	0.0 Percentage of participants	1.5 Percentage of participants	4.7 Percentage of participants	3.1 Percentage of participants	6.1 Percentage of participants	0.0 Percentage of participants	2.6 Percentage of participants	13.0 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk12,n=130,115,123,129,39,37,23,21,94,17,18	4.8 Percentage of participants	14.9 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	3.1 Percentage of participants	3.5 Percentage of participants	3.3 Percentage of participants	10.9 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	13.0 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk16,n=126,118,116,129,36,37,21,22,94,16,19	4.5 Percentage of participants	13.8 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	6.3 Percentage of participants	9.3 Percentage of participants	3.4 Percentage of participants	10.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	14.3 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk20,n=122,114,119,126,38,37,23,21,91,16,19	14.3 Percentage of participants	15.4 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	6.6 Percentage of participants	8.8 Percentage of participants	6.7 Percentage of participants	11.1 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	21.7 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk24,n=117,110,117,121,38,36,21,22,87,16,18	9.1 Percentage of participants	19.5 Percentage of participants	0.0 Percentage of participants	5.6 Percentage of participants	6.0 Percentage of participants	12.7 Percentage of participants	8.5 Percentage of participants	14.9 Percentage of participants	0.0 Percentage of participants	8.3 Percentage of participants	23.8 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk28,n=115,103,na,na,33,35,21,21,86,17,19	14.3 Percentage of participants	17.4 Percentage of participants	5.9 Percentage of participants	0.0 Percentage of participants	6.1 Percentage of participants	17.5 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	0.0 Percentage of participants	2.9 Percentage of participants	14.3 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk32,n=104,97,na,na,33,30,21,19,87,17,17	0.0 Percentage of participants	21.8 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	4.8 Percentage of participants	10.0 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	0.0 Percentage of participants	3.3 Percentage of participants	19.0 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk36,n=102,93,na,na,30,30,21,20,85,18,16	0.0 Percentage of participants	23.5 Percentage of participants	11.1 Percentage of participants	0.0 Percentage of participants	5.9 Percentage of participants	11.8 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	3.3 Percentage of participants	0.0 Percentage of participants	23.8 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk40,n=96,90,na,na,28,28,21,19,85,15,17	10.5 Percentage of participants	21.2 Percentage of participants	13.3 Percentage of participants	0.0 Percentage of participants	8.3 Percentage of participants	11.1 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	7.1 Percentage of participants	10.7 Percentage of participants	19.0 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk44,n=97,90,na,na,28,27,20,18,84,15,16	11.1 Percentage of participants	26.2 Percentage of participants	6.7 Percentage of participants	0.0 Percentage of participants	12.4 Percentage of participants	18.9 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	0.0 Percentage of participants	11.1 Percentage of participants	25.0 Percentage of participants
Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data ACR70,wk52,n=92,88,na,na,28,26,20,18,79,15,15	16.7 Percentage of participants	22.8 Percentage of participants	13.3 Percentage of participants	0.0 Percentage of participants	6.5 Percentage of participants	19.3 Percentage of participants	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA Percentage of participants After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	0.0 Percentage of participants	7.7 Percentage of participants	30.0 Percentage of participants

SECONDARY outcome

Timeframe: baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24

Population: Participants from the full analysis set were considered for this analysis. For Placebo and Abatacept participants, data collected after treatment switch was treated as missing, as were missing values for all treatment groups.

The HAQ-DI, assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo Responder - AIN457 150mg Participants switched from placebo to AIN457 150 mg starting at week 24.	Abatacept Responders Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).	Abatacept Non-responders - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.	Abatacept Non-responders - AIN457 150mg Participants switched from abatacept to AIN457 150 mg starting at week 24.	AIN457 10mg/kg - 75 mg n=138 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=137 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=138 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=138 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Placebo Non-responder - AIN457 75 mg Participants switched from placebo to AIN457 75 mg starting at week 16.	Placebo Non-responder - AIN457 150 mg Participants switched from placebo to AIN457 150 mg starting at week 16.	Placebo Responder - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.
Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM) week 1, n=132,129,130,129	—	—	—	—	-0.22 score on a scale Standard Error 0.032	-0.21 score on a scale Standard Error 0.032	-0.08 score on a scale Standard Error 0.032	-0.19 score on a scale Standard Error 0.032	—	—	—
Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM) week 2, n=131,130,134,133	—	—	—	—	-0.22 score on a scale Standard Error 0.036	-0.25 score on a scale Standard Error 0.036	-0.16 score on a scale Standard Error 0.036	-0.26 score on a scale Standard Error 0.036	—	—	—
Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM) week 4, n=133,133,131,130	—	—	—	—	-0.30 score on a scale Standard Error 0.039	-0.31 score on a scale Standard Error 0.040	-0.17 score on a scale Standard Error 0.040	-0.36 score on a scale Standard Error 0.040	—	—	—
Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM) week 8, n=132,127,131,130	—	—	—	—	-0.29 score on a scale Standard Error 0.042	-0.32 score on a scale Standard Error 0.043	-0.17 score on a scale Standard Error 0.043	-0.46 score on a scale Standard Error 0.043	—	—	—
Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM) week 12, n=130,114,123,129	—	—	—	—	-0.31 score on a scale Standard Error 0.046	-0.33 score on a scale Standard Error 0.047	-0.18 score on a scale Standard Error 0.047	-0.51 score on a scale Standard Error 0.046	—	—	—
Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM) week 16, n=127,118,116,129	—	—	—	—	-0.30 score on a scale Standard Error 0.048	-0.37 score on a scale Standard Error 0.049	-0.22 score on a scale Standard Error 0.049	-0.52 score on a scale Standard Error 0.048	—	—	—
Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM) week 20, n=122,114,47,92	—	—	—	—	-0.36 score on a scale Standard Error 0.051	-0.42 score on a scale Standard Error 0.052	-0.21 score on a scale Standard Error 0.066	-0.57 score on a scale Standard Error 0.054	—	—	—
Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM) week 24, n=117,110,44,86	—	—	—	—	-0.30 score on a scale Standard Error 0.049	-0.39 score on a scale Standard Error 0.051	-0.26 score on a scale Standard Error 0.065	-0.61 score on a scale Standard Error 0.053	—	—	—

SECONDARY outcome

Timeframe: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Population: Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and each post-baseline time point were analyzed for that post-baseline time point. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.

The HAQ-DI assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement. The HAQ-DI results from baseline up to week 52 were based on observed data, i.e. without imputation.

Outcome measures

Measure	Placebo Responder - AIN457 150mg n=22 Participants Participants switched from placebo to AIN457 150 mg starting at week 24.	Abatacept Responders n=101 Participants Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).	Abatacept Non-responders - AIN457 75mg n=18 Participants Participants switched from placebo to AIN457 75 mg starting at week 24.	Abatacept Non-responders - AIN457 150mg n=19 Participants Participants switched from abatacept to AIN457 150 mg starting at week 24.	AIN457 10mg/kg - 75 mg n=138 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=137 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=138 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=138 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Placebo Non-responder - AIN457 75 mg n=39 Participants Participants switched from placebo to AIN457 75 mg starting at week 16.	Placebo Non-responder - AIN457 150 mg n=39 Participants Participants switched from placebo to AIN457 150 mg starting at week 16.	Placebo Responder - AIN457 75mg n=23 Participants Participants switched from placebo to AIN457 75 mg starting at week 24.
Change From Baseline in HAQ-DI - Observed Data wk1,n=132,129,130,129,39,35,21,22,95,17,17	-0.153 score on a scale Standard Deviation 0.2468	-0.232 score on a scale Standard Deviation 0.4551	-0.081 score on a scale Standard Deviation 0.3616	-0.096 score on a scale Standard Deviation 0.3047	-0.225 score on a scale Standard Deviation 0.3766	-0.215 score on a scale Standard Deviation 0.4095	-0.101 score on a scale Standard Deviation 0.3186	-0.194 score on a scale Standard Deviation 0.4290	-0.119 score on a scale Standard Deviation 0.2896	-0.079 score on a scale Standard Deviation 0.3093	-0.125 score on a scale Standard Deviation 0.4257
Change From Baseline in HAQ-DI - Observed Data Wk2,n=131,130,134,133,39,36,23,22,133,98,17,18	-0.250 score on a scale Standard Deviation 0.5015	-0.300 score on a scale Standard Deviation 0.4693	-0.132 score on a scale Standard Deviation 0.3630	-0.118 score on a scale Standard Deviation 0.3987	-0.215 score on a scale Standard Deviation 0.3877	-0.239 score on a scale Standard Deviation 0.4885	-0.191 score on a scale Standard Deviation 0.4340	-0.254 score on a scale Standard Deviation 0.4520	-0.122 score on a scale Standard Deviation 0.2605	-0.176 score on a scale Standard Deviation 0.4631	-0.380 score on a scale Standard Deviation 0.5063
Change From Baseline in HAQ-DI - Observed Data Wk4,n=133,133,131,130,39,39,23,21,94,17,19	-0.310 score on a scale Standard Deviation 0.3103	-0.445 score on a scale Standard Deviation 0.5245	-0.110 score on a scale Standard Deviation 0.3505	-0.217 score on a scale Standard Deviation 0.4874	-0.299 score on a scale Standard Deviation 0.4551	-0.300 score on a scale Standard Deviation 0.5184	-0.214 score on a scale Standard Deviation 0.4492	-0.368 score on a scale Standard Deviation 0.5130	-0.077 score on a scale Standard Deviation 0.3634	-0.224 score on a scale Standard Deviation 0.4968	-0.364 score on a scale Standard Deviation 0.5627
Change From Baseline in HAQ-DI - Observed Data Wk8,n=132,127,131,130,39,39,23,22,94,17,19	-0.176 score on a scale Standard Deviation 0.4782	-0.543 score on a scale Standard Deviation 0.5289	-0.206 score on a scale Standard Deviation 0.4900	-0.303 score on a scale Standard Deviation 0.3780	-0.277 score on a scale Standard Deviation 0.5062	-0.309 score on a scale Standard Deviation 0.5175	-0.217 score on a scale Standard Deviation 0.5457	-0.463 score on a scale Standard Deviation 0.5182	-0.186 score on a scale Standard Deviation 0.5097	-0.128 score on a scale Standard Deviation 0.5077	-0.543 score on a scale Standard Deviation 0.6313
Change From Baseline in HAQ-DI - Observed Data wk12,n=130,114,123,129,39,37,23,21,94,17,18	-0.381 score on a scale Standard Deviation 0.3982	-0.622 score on a scale Standard Deviation 0.6520	-0.221 score on a scale Standard Deviation 0.4274	-0.181 score on a scale Standard Deviation 0.5376	-0.287 score on a scale Standard Deviation 0.5384	-0.307 score on a scale Standard Deviation 0.5488	-0.241 score on a scale Standard Deviation 0.5152	-0.508 score on a scale Standard Deviation 0.6369	-0.109 score on a scale Standard Deviation 0.4783	-0.179 score on a scale Standard Deviation 0.5133	-0.451 score on a scale Standard Deviation 0.6167
Change From Baseline in HAQ-DI - Observed Data Wk16,n=127,118,116,129,36,37,21,22,94,16,19	-0.472 score on a scale Standard Deviation 0.5988	-0.660 score on a scale Standard Deviation 0.6590	-0.195 score on a scale Standard Deviation 0.4281	-0.204 score on a scale Standard Deviation 0.4827	-0.294 score on a scale Standard Deviation 0.5236	-0.355 score on a scale Standard Deviation 0.6217	-0.279 score on a scale Standard Deviation 0.5493	-0.535 score on a scale Standard Deviation 0.6418	-0.167 score on a scale Standard Deviation 0.5295	-0.111 score on a scale Standard Deviation 0.4591	-0.565 score on a scale Standard Deviation 0.5356
Change From Baseline in HAQ-DI - Observed Data Wk20,n=122,114,119,125,38,37,23,21,90,16,19	-0.470 score on a scale Standard Deviation 0.7309	-0.699 score on a scale Standard Deviation 0.6849	-0.086 score on a scale Standard Deviation 0.3972	-0.454 score on a scale Standard Deviation 0.5436	-0.333 score on a scale Standard Deviation 0.5111	-0.402 score on a scale Standard Deviation 0.6429	-0.319 score on a scale Standard Deviation 0.5637	-0.583 score on a scale Standard Deviation 0.6654	-0.237 score on a scale Standard Deviation 0.4756	-0.179 score on a scale Standard Deviation 0.5158	-0.543 score on a scale Standard Deviation 0.5325
Change From Baseline in HAQ-DI - Observed Data Wk24,n=117,110,117,120,38,36,21,22,86,16,18	-0.420 score on a scale Standard Deviation 0.6732	-0.744 score on a scale Standard Deviation 0.6787	-0.180 score on a scale Standard Deviation 0.4257	-0.215 score on a scale Standard Deviation 0.6443	-0.268 score on a scale Standard Deviation 0.4930	-0.405 score on a scale Standard Deviation 0.5767	0.346 score on a scale Standard Deviation 0.5941	-0.590 score on a scale Standard Deviation 0.6872	-0.257 score on a scale Standard Deviation 0.4730	-0.253 score on a scale Standard Deviation 0.6502	-0.589 score on a scale Standard Deviation 0.5648
Change From Baseline in HAQ-DI - Observed Data Wk28,n=115,102,na,na,33,35,21,21,86,17,19	-0.601 score on a scale Standard Deviation 0.5571	-0.689 score on a scale Standard Deviation 0.6428	-0.309 score on a scale Standard Deviation 0.5522	-0.303 score on a scale Standard Deviation 0.5882	-0.304 score on a scale Standard Deviation 0.5342	-0.439 score on a scale Standard Deviation 0.5780	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-0.345 score on a scale Standard Deviation 0.5880	-0.336 score on a scale Standard Deviation 0.5846	-0.625 score on a scale Standard Deviation 0.4809
Change From Baseline in HAQ-DI - Observed Data Wk32,n=104,97,na,na,33,30,21,19,87,17,17	-0.546 score on a scale Standard Deviation 0.5998	-0.741 score on a scale Standard Deviation 0.6909	-0.228 score on a scale Standard Deviation 0.5612	-0.375 score on a scale Standard Deviation 0.7315	-0.358 score on a scale Standard Deviation 0.4964	-0.505 score on a scale Standard Deviation 0.5759	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-0.284 score on a scale Standard Deviation 0.4627	-0.300 score on a scale Standard Deviation 0.5039	-0.679 score on a scale Standard Deviation 0.5414
Change From Baseline in HAQ-DI - Observed Data Wk36,n=102,93,na,na,30,30,21,19,84,18,16,	-0.474 score on a scale Standard Deviation 0.6032	-0.756 score on a scale Standard Deviation 0.6844	-0.285 score on a scale Standard Deviation 0.5891	-0.430 score on a scale Standard Deviation 0.6723	-0.339 score on a scale Standard Deviation 0.5687	-0.430 score on a scale Standard Deviation 0.5573	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-0.368 score on a scale Standard Deviation 0.5397	-0.383 score on a scale Standard Deviation 0.4500	-0.607 score on a scale Standard Deviation 0.5538
Change From Baseline in HAQ-DI - Observed Data Wk40,n=96,89,na,na,28,28,21,19,84,15,17	-0.539 score on a scale Standard Deviation 0.6998	-0.763 score on a scale Standard Deviation 0.6750	-0.242 score on a scale Standard Deviation 0.6312	-0.390 score on a scale Standard Deviation 0.6523	-0.424 score on a scale Standard Deviation 0.5967	-0.440 score on a scale Standard Deviation 0.5416	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-0.522 score on a scale Standard Deviation 0.6805	-0.391 score on a scale Standard Deviation 0.5446	-0.571 score on a scale Standard Deviation 0.5736
Change From Baseline in HAQ-DI - Observed Data Wk44,n=97,90,na,na,28,27,20,18,84,15,16	-0.514 score on a scale Standard Deviation 0.7752	-0.781 score on a scale Standard Deviation 0.7252	-0.308 score on a scale Standard Deviation 0.6319	-0.203 score on a scale Standard Deviation 0.7917	-0.331 score on a scale Standard Deviation 0.5871	-0.449 score on a scale Standard Deviation 0.5427	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-0.277 score on a scale Standard Deviation 0.6377	-0.523 score on a scale Standard Deviation 0.6587	-0.638 score on a scale Standard Deviation 0.5144
Change From Baseline in HAQ-DI - Observed Data Wk48,n-94,89,na,na,28,26,19,19,76,12,14	-0.454 score on a scale Standard Deviation 0.5547	-0.798 score on a scale Standard Deviation 0.6481	-0.229 score on a scale Standard Deviation 0.6546	-0.286 score on a scale Standard Deviation 0.7618	-0.303 score on a scale Standard Deviation 0.5062	-0.483 score on a scale Standard Deviation 0.5459	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-0.348 score on a scale Standard Deviation 0.5886	-0.413 score on a scale Standard Deviation 0.5698	-0.605 score on a scale Standard Deviation 0.6113
Change From Baseline in HAQ-DI - Observed Data Wk52,n=92,87,na,na,28,26,20,18,79,15,15	-0.569 score on a scale Standard Deviation 0.7126	-0.788 score on a scale Standard Deviation 0.6853	-0.392 score on a scale Standard Deviation 0.5216	-0.258 score on a scale Standard Deviation 0.8298	-0.341 score on a scale Standard Deviation 0.5428	-0.516 score on a scale Standard Deviation 0.6036	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-0.402 score on a scale Standard Deviation 0.5436	-0.351 score on a scale Standard Deviation 0.6335	-0.606 score on a scale Standard Deviation 0.6492

SECONDARY outcome

Timeframe: baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24

Population: Participants from the full analysis set were considered for the analysis. For Placebo and Abatacept participants, data collected after treatment switch was treated as missing, as were missing values for all treatment groups

The DAS28 is a measure of disease activity in RA based on Swollen and Tender Joint Counts (out of a total of 28), hsCRP and the Patient's Global Assessment of Disease Activity. A DAS28 score greater than 5.1 implies active disease, equal to or less than 3.2 low disease activity, and less than 2.6 remission. A negative change from baseline indicates improvement.

Outcome measures

Measure	Placebo Responder - AIN457 150mg Participants switched from placebo to AIN457 150 mg starting at week 24.	Abatacept Responders Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).	Abatacept Non-responders - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.	Abatacept Non-responders - AIN457 150mg Participants switched from abatacept to AIN457 150 mg starting at week 24.	AIN457 10mg/kg - 75 mg n=138 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=137 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=138 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=39 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Placebo Non-responder - AIN457 75 mg Participants switched from placebo to AIN457 75 mg starting at week 16.	Placebo Non-responder - AIN457 150 mg Participants switched from placebo to AIN457 150 mg starting at week 16.	Placebo Responder - AIN457 75mg Participants switched from placebo to AIN457 75 mg starting at week 24.
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Using MMRM week 1, n=131,129,130,129	—	—	—	—	-0.89 score on a scale Standard Error 0.069	-0.73 score on a scale Standard Error 0.069	-0.22 score on a scale Standard Error 0.069	-0.50 score on a scale Standard Error 0.069	—	—	—
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Using MMRM week 2, n=131,127,132,133	—	—	—	—	-0.96 score on a scale Standard Error 0.080	-0.90 score on a scale Standard Error 0.081	-0.35 score on a scale Standard Error 0.080	-0.78 score on a scale Standard Error 0.080	—	—	—
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Using MMRM week 4, n=130,131,138,138	—	—	—	—	-1.20 score on a scale Standard Error 0.090	-1.11 score on a scale Standard Error 0.090	-0.48 score on a scale Standard Error 0.090	-1.11 score on a scale Standard Error 0.091	—	—	—
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Using MMRM week 8, n=130,126,130,130	—	—	—	—	-1.21 score on a scale Standard Error 0.093	-1.23 score on a scale Standard Error 0.094	-0.61 score on a scale Standard Error 0.093	-1.55 score on a scale Standard Error 0.093	—	—	—
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Using MMRM week 12, n=130,114,123,128	—	—	—	—	-1.23 score on a scale Standard Error 0.097	-1.36 score on a scale Standard Error 0.102	-0.73 score on a scale Standard Error 0.100	-1.78 score on a scale Standard Error 0.098	—	—	—
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Using MMRM week 16, n=126,116,114,127	—	—	—	—	-1.23 score on a scale Standard Error 0.108	-1.40 score on a scale Standard Error 0.112	-0.57 score on a scale Standard Error 0.112	-1.71 score on a scale Standard Error 0.108	—	—	—
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Using MMRM week 20, n=121,114,47,92	—	—	—	—	-1.44 score on a scale Standard Error 0.108	-1.49 score on a scale Standard Error 0.111	-0.89 score on a scale Standard Error 0.146	-1.96 score on a scale Standard Error 0.117	—	—	—
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Using MMRM week 24, n=116,108,44,84	—	—	—	—	-1.47 score on a scale Standard Error 0.115	-1.47 score on a scale Standard Error 0.119	-1.02 score on a scale Standard Error 0.163	-2.07 score on a scale Standard Error 0.128	—	—	—

SECONDARY outcome

Timeframe: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Population: Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and each post-baseline time point were analyzed for that post-baseline time point. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.

The DAS28 is a measure of disease activity in RA based on Swollen and Tender Joint Counts (out of a total of 28), hsCRP and the Patient's Global Assessment of Disease Activity. A DAS28 score greater than 5.1 implies active disease, equal to or less than 3.2 low disease activity, and less than 2.6 remission. A negative change from baseline indicates improvement. The DAS28-CRP results from baseline up to week 52 were based on observed data, i.e. without imputation.

Outcome measures

Measure	Placebo Responder - AIN457 150mg n=138 Participants Participants switched from placebo to AIN457 150 mg starting at week 24.	Abatacept Responders n=101 Participants Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).	Abatacept Non-responders - AIN457 75mg n=18 Participants Participants switched from placebo to AIN457 75 mg starting at week 24.	Abatacept Non-responders - AIN457 150mg n=19 Participants Participants switched from abatacept to AIN457 150 mg starting at week 24.	AIN457 10mg/kg - 75 mg n=138 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=137 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=138 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=39 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Placebo Non-responder - AIN457 75 mg n=39 Participants Participants switched from placebo to AIN457 75 mg starting at week 16.	Placebo Non-responder - AIN457 150 mg n=23 Participants Participants switched from placebo to AIN457 150 mg starting at week 16.	Placebo Responder - AIN457 75mg n=22 Participants Participants switched from placebo to AIN457 75 mg starting at week 24.
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk32,n=103,97,na,na,33,39,23,22,87,17,16	-1.875 score on a scale Standard Deviation 0.9807	-2.629 score on a scale Standard Deviation 1.3104	-0.961 score on a scale Standard Deviation 1.0043	-1.464 score on a scale Standard Deviation 1.2025	-1.738 score on a scale Standard Deviation 1.2783	-1.966 score on a scale Standard Deviation 1.1770	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-1.408 score on a scale Standard Deviation 1.3855	-1.475 score on a scale Standard Deviation 1.1846	-2.363 score on a scale Standard Deviation 1.0711
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk36,n=101,92,na,na,30,30,21,20,84,18,15	-1.784 score on a scale Standard Deviation 0.9029	-2.642 score on a scale Standard Deviation 1.4305	-1.200 score on a scale Standard Deviation 1.3228	-1.425 score on a scale Standard Deviation 0.9247	-1.737 score on a scale Standard Deviation 1.4592	-1.820 score on a scale Standard Deviation 1.2500	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-1.271 score on a scale Standard Deviation 1.4949	-1.444 score on a scale Standard Deviation 1.1949	-2.269 score on a scale Standard Deviation 1.0688
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk40,n=96,90,na,na,28,28,21,19,84,15,17	-2.134 score on a scale Standard Deviation 1.0405	-2.549 score on a scale Standard Deviation 1.3305	-1.201 score on a scale Standard Deviation 1.5293	-1.612 score on a scale Standard Deviation 1.1839	-1.742 score on a scale Standard Deviation 1.3259	-1.788 score on a scale Standard Deviation 1.1333	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-1.354 score on a scale Standard Deviation 1.3590	-1.494 score on a scale Standard Deviation 1.3243	-2.315 score on a scale Standard Deviation 1.0773
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk44,n=96,88,na,na,28,27,20,18,84,15,16	-2.121 score on a scale Standard Deviation 1.1347	-2.697 score on a scale Standard Deviation 1.2117	-0.881 score on a scale Standard Deviation 1.3337	-1.528 score on a scale Standard Deviation 1.2973	-1.764 score on a scale Standard Deviation 1.3227	-1.932 score on a scale Standard Deviation 1.2850	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-1.168 score on a scale Standard Deviation 1.2638	-1.858 score on a scale Standard Deviation 1.2373	-2.155 score on a scale Standard Deviation 0.9488
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk48,n=94,88,na,na,28,26,18,19,76,12,14	-1.964 score on a scale Standard Deviation 1.3404	-2.634 score on a scale Standard Deviation 1.2189	-1.013 score on a scale Standard Deviation 1.1738	-1.400 score on a scale Standard Deviation 1.1985	-1.761 score on a scale Standard Deviation 1.3152	-2.200 score on a scale Standard Deviation 1.3293	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-1.516 score on a scale Standard Deviation 1.0635	-1.660 score on a scale Standard Deviation 1.1805	-2.259 score on a scale Standard Deviation 1.1813
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk52,n=92,86,na,na,28,26,20,18,79,15,15	-2.334 score on a scale Standard Deviation 1.1428	-2.676 score on a scale Standard Deviation 1.3593	-1.390 score on a scale Standard Deviation 1.1884	-0.982 score on a scale Standard Deviation 1.1943	-1.839 score on a scale Standard Deviation 1.3755	-2.109 score on a scale Standard Deviation 1.4000	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-1.487 score on a scale Standard Deviation 1.0729	-1.690 score on a scale Standard Deviation 1.2093	-2.070 score on a scale Standard Deviation 0.9984
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk28,n=115,103,na,na,33,35,21,21,86,17,18	-1.782 score on a scale Standard Deviation 1.0655	-2.470 score on a scale Standard Deviation 1.2153	-1.137 score on a scale Standard Deviation 1.2050	-0.973 score on a scale Standard Deviation 1.1034	-1.484 score on a scale Standard Deviation 1.3216	-1.819 score on a scale Standard Deviation 1.3434	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA score on a scale Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-1.172 score on a scale Standard Deviation 1.1602	-1.244 score on a scale Standard Deviation 1.2433	-2.117 score on a scale Standard Deviation 0.8573
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk1,n=131,129,130,129,39,35,21,22, 95,17,17	-0.235 score on a scale Standard Deviation 0.7699	-0.577 score on a scale Standard Deviation 0.7924	-0.361 score on a scale Standard Deviation 0.3578	-0.222 score on a scale Standard Deviation 0.7695	-0.886 score on a scale Standard Deviation 0.9784	-0.759 score on a scale Standard Deviation 0.8654	-0.211 score on a scale Standard Deviation 0.6877	-0.502 score on a scale Standard Deviation 0.7539	-0.147 score on a scale Standard Deviation 0.5527	-0.141 score on a scale Standard Deviation 0.7095	-0.572 score on a scale Standard Deviation 0.7856
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk2,n=131,127,132,133,39,36,23,21,98,17,18	-0.292 score on a scale Standard Deviation 0.7448	-0.755 score on a scale Standard Deviation 0.9234	-0.882 score on a scale Standard Deviation 0.9526	-0.359 score on a scale Standard Deviation 0.8980	-0.909 score on a scale Standard Deviation 1.0331	-0.900 score on a scale Standard Deviation 1.0284	-0.363 score on a scale Standard Deviation 0.8388	-0.755 score on a scale Standard Deviation 0.9234	-0.191 score on a scale Standard Deviation 0.7331	-0.368 score on a scale Standard Deviation 0.7170	-0.835 score on a scale Standard Deviation 0.9466
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk4,n=130,131,129,128,39,38,23,21,92,17,19	-0.767 score on a scale Standard Deviation 0.9661	-1.268 score on a scale Standard Deviation 1.0533	-0.595 score on a scale Standard Deviation 1.1160	-0.706 score on a scale Standard Deviation 0.6999	-1.163 score on a scale Standard Deviation 1.1656	-1.150 score on a scale Standard Deviation 1.1942	-0.492 score on a scale Standard Deviation 0.8876	-1.095 score on a scale Standard Deviation 1.0483	-0.252 score on a scale Standard Deviation 0.8116	-0.352 score on a scale Standard Deviation 0.7471	-1.034 score on a scale Standard Deviation 0.9119
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk8,n=130,126,130,130,39,39,23,22,94,17,19	-0.613 score on a scale Standard Deviation 0.9772	-1.816 score on a scale Standard Deviation 1.0708	-0.834 score on a scale Standard Deviation 1.1469	-0.808 score on a scale Standard Deviation 0.6444	-1.181 score on a scale Standard Deviation 1.1821	-1.283 score on a scale Standard Deviation 1.1678	-0.644 score on a scale Standard Deviation 1.1356	-1.541 score on a scale Standard Deviation 1.1172	-0.546 score on a scale Standard Deviation 1.1597	-0.312 score on a scale Standard Deviation 0.9151	-1.403 score on a scale Standard Deviation 1.2060
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk12,n=130,114,123,128,39,37,23,21,93,17,18	-1.330 score on a scale Standard Deviation 1.4721	-2.144 score on a scale Standard Deviation 1.1028	-0.749 score on a scale Standard Deviation 1.0757	-0.945 score on a scale Standard Deviation 1.1008	-1.229 score on a scale Standard Deviation 1.1782	-1.402 score on a scale Standard Deviation 1.2182	-0.742 score on a scale Standard Deviation 1.2330	-1.790 score on a scale Standard Deviation 1.2356	-0.311 score on a scale Standard Deviation 0.9514	-0.383 score on a scale Standard Deviation 1.1765	-1.588 score on a scale Standard Deviation 0.9714
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk16,n=126,116,114,128,36,36,21,21,94,15,19	-1.503 score on a scale Standard Deviation 0.8746	-2.159 score on a scale Standard Deviation 1.0767	-0.490 score on a scale Standard Deviation 0.8170	-0.322 score on a scale Standard Deviation 1.0262	-1.225 score on a scale Standard Deviation 1.2866	-1.455 score on a scale Standard Deviation 1.3489	-0.592 score on a scale Standard Deviation 1.2557	-1.691 score on a scale Standard Deviation 1.2979	0.128 score on a scale Standard Deviation 0.8579	0.045 score on a scale Standard Deviation 0.9145	-2.008 score on a scale Standard Deviation 0.8675
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk20,n=121,114,,119,125,38,37,23,21,90,16,19	-1.399 score on a scale Standard Deviation 1.1487	-2.317 score on a scale Standard Deviation 1.2549	-0.402 score on a scale Standard Deviation 0.9820	-0.792 score on a scale Standard Deviation 1.0272	-1.427 score on a scale Standard Deviation 1.3266	-1.569 score on a scale Standard Deviation 1.2361	-1.164 score on a scale Standard Deviation 1.2087	-1.840 score on a scale Standard Deviation 1.4144	-0.683 score on a scale Standard Deviation 1.1231	-0.937 score on a scale Standard Deviation 1.0966	-2.108 score on a scale Standard Deviation 1.0368
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data Wk24,n=116,108,116,117,37,36,21,22,84,15,18	-1.362 score on a scale Standard Deviation 1.2999	-2.435 score on a scale Standard Deviation 1.3266	-0.772 score on a scale Standard Deviation 1.1656	-0.923 score on a scale Standard Deviation 1.2560	-1.467 score on a scale Standard Deviation 1.3116	-1.579 score on a scale Standard Deviation 1.3221	-1.248 score on a scale Standard Deviation 1.2915	-1.989 score on a scale Standard Deviation 1.4717	-0.666 score on a scale Standard Deviation 0.9983	-1.140 score on a scale Standard Deviation 1.1954	-2.343 score on a scale Standard Deviation 1.2649

SECONDARY outcome

Timeframe: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Population: Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and each post-baseline time point were analyzed for that post-baseline time point. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.

Blood samples were obtained to identify the presence of inflammation, to determine its severity and to monitor response to treatment. A negative change from baseline indicates improvement. The hsCRP results from baseline up to week 52 were based on observed data, i.e. without imputation.

Outcome measures

Measure	Placebo Responder - AIN457 150mg n=22 Participants Participants switched from placebo to AIN457 150 mg starting at week 24.	Abatacept Responders n=101 Participants Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).	Abatacept Non-responders - AIN457 75mg n=18 Participants Participants switched from placebo to AIN457 75 mg starting at week 24.	Abatacept Non-responders - AIN457 150mg n=19 Participants Participants switched from abatacept to AIN457 150 mg starting at week 24.	AIN457 10mg/kg - 75 mg n=138 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=137 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=138 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=138 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Placebo Non-responder - AIN457 75 mg n=39 Participants Participants switched from placebo to AIN457 75 mg starting at week 16.	Placebo Non-responder - AIN457 150 mg n=39 Participants Participants switched from placebo to AIN457 150 mg starting at week 16.	Placebo Responder - AIN457 75mg n=23 Participants Participants switched from placebo to AIN457 75 mg starting at week 24.
Change From Baseline in hsCRP - Observed Data Wk1,n=134,130,131,131,39,36,21,22,97,17,17	-1.50 mg/L Standard Deviation 7.541	-6.40 mg/L Standard Deviation 20.458	-2.92 mg/L Standard Deviation 12.405	-4.07 mg/L Standard Deviation 10.811	-10.91 mg/L Standard Deviation 30.815	-10.31 mg/L Standard Deviation 27.754	-0.69 mg/L Standard Deviation 15.521	-5.64 mg/L Standard Deviation 18.550	-0.33 mg/L Standard Deviation 10.430	-0.84 mg/L Standard Deviation 24.777	-0.40 mg/L Standard Deviation 12.244
Change From Baseline in hsCRP - Observed Data Wk2,n=133,129,133,135,39,36,23,21,100,17,18	-4.78 mg/L Standard Deviation 10.515	-7.52 mg/L Standard Deviation 20.301	-3.84 mg/L Standard Deviation 13.737	-2.30 mg/L Standard Deviation 19.035	-10.24 mg/L Standard Deviation 33.209	-11.51 mg/L Standard Deviation 32.139	-2.21 mg/L Standard Deviation 14.501	-6.36 mg/L Standard Deviation 19.416	0.43 mg/L Standard Deviation 15.333	-5.48 mg/L Standard Deviation 17.301	-1.70 mg/L Standard Deviation 11.170
Change From Baseline in hsCRP - Observed Data Wk4,n=131,134,129,133,39,38,23,21,97,17,19	-1.95 mg/L Standard Deviation 12.090	-7.53 mg/L Standard Deviation 22.982	-4.42 mg/L Standard Deviation 14.991	-4.50 mg/L Standard Deviation 11.029	-9.10 mg/L Standard Deviation 20.514	-10.76 mg/L Standard Deviation 33.376	-1.53 mg/L Standard Deviation 19.311	-6.70 mg/L Standard Deviation 20.732	2.23 mg/L Standard Deviation 23.317	-1.94 mg/L Standard Deviation 21.927	-6.47 mg/L Standard Deviation 12.458
Change From Baseline in hsCRP - Observed Data Wk8,n=134,128,130,132,39,39,23,22,96,17,19	-1.50 mg/L Standard Deviation 12.839	-10.13 mg/L Standard Deviation 22.724	-.54 mg/L Standard Deviation 14.849	-4.59 mg/L Standard Deviation 16.603	-10.18 mg/L Standard Deviation 33.400	-12.94 mg/L Standard Deviation 30.854	-2.94 mg/L Standard Deviation 20.601	-8.48 mg/L Standard Deviation 21.134	-4.72 mg/L Standard Deviation 18.766	-3.28 mg/L Standard Deviation 25.501	0.13 mg/L Standard Deviation 18.061
Change From Baseline in hsCRP - Observed Data Wk12,n=133,119,128,131,39,39,23,22,96,17,18	2.10 mg/L Standard Deviation 22.545	-12.17 mg/L Standard Deviation 25.813	-4.18 mg/L Standard Deviation 16.024	-1.94 mg/L Standard Deviation 31.483	-9.41 mg/L Standard Deviation 31.859	-9.66 mg/L Standard Deviation 24.298	-0.69 mg/L Standard Deviation 18.908	-9.72 mg/L Standard Deviation 25.787	2.11 mg/L Standard Deviation 18.312	-2.89 mg/L Standard Deviation 20.763	-2.74 mg/L Standard Deviation 12.899
Change From Baseline in hsCRP - Observed Data Wk16,n=129,120,121,131,36,38,21,21,96,16,19	-4.29 mg/L Standard Deviation 13.497	-11.25 mg/L Standard Deviation 23.692	-1.41 mg/L Standard Deviation 8.810	0.32 mg/L Standard Deviation 22.024	-9.97 mg/L Standard Deviation 33.291	-5.78 mg/L Standard Deviation 25.418	-1.82 mg/L Standard Deviation 20.849	-8.37 mg/L Standard Deviation 22.571	3.92 mg/L Standard Deviation 23.403	-2.13 mg/L Standard Deviation 24.422	-5.67 mg/L Standard Deviation 9.583
Change From Baseline in hsCRP - Observed Data Wk20,n=124,116,120,127,38,37,23,21,91,17,19	-1.06 mg/L Standard Deviation 15.737	-11.59 mg/L Standard Deviation 24.271	-3.94 mg/L Standard Deviation 15.716	-3.99 mg/L Standard Deviation 32.871	-9.19 mg/L Standard Deviation 32.876	-8.05 mg/L Standard Deviation 22.394	-3.75 mg/L Standard Deviation 29.301	-9.43 mg/L Standard Deviation 23.212	-5.33 mg/L Standard Deviation 20.645	-7.77 mg/L Standard Deviation 27.581	3.23 mg/L Standard Deviation 48.634
Change From Baseline in hsCRP - Observed Data Wk24,n=121,113,116,120,37,36,21,22,86,16,18	0.45 mg/L Standard Deviation 18.244	-11.72 mg/L Standard Deviation 22.198	-4.94 mg/L Standard Deviation 13.605	2.63 mg/L Standard Deviation 20.875	-6.90 mg/L Standard Deviation 22.098	-4.92 mg/L Standard Deviation 23.075	-6.88 mg/L Standard Deviation 21.014	-8.66 mg/L Standard Deviation 21.574	-7.06 mg/L Standard Deviation 20.298	-11.46 mg/L Standard Deviation 26.373	-6.40 mg/L Standard Deviation 11.562
Change From Baseline in hsCRP - Observed Data Wk28,n=119,110,na,na,34,35,21,21,89,17,18	0.09 mg/L Standard Deviation 24.933	-12.08 mg/L Standard Deviation 22.791	-4.51 mg/L Standard Deviation 14.144	-1.70 mg/L Standard Deviation 22.671	-4.94 mg/L Standard Deviation 23.155	-5.87 mg/L Standard Deviation 25.885	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-4.43 mg/L Standard Deviation 21.777	-11.10 mg/L Standard Deviation 27.186	-7.97 mg/L Standard Deviation 18.018
Change From Baseline in hsCRP - Observed Data Wk32,n=107,101,na,na,34,32,20,21,87,17,16	-5.51 mg/L Standard Deviation 14.279	-12.83 mg/L Standard Deviation 23.330	-4.26 mg/L Standard Deviation 15.329	-7.14 mg/L Standard Deviation 17.446	-8.57 mg/L Standard Deviation 20.826	7.37 mg/L Standard Deviation 24.564	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-4.34 mg/L Standard Deviation 23.742	-9.08 mg/L Standard Deviation 25.867	-5.02 mg/L Standard Deviation 10.300
Change From Baseline in hsCRP - Observed Data Wk36,n=107,98,na,na,32,31,21,20,85,18,15	-6.78 mg/L Standard Deviation 13.940	-12.19 mg/L Standard Deviation 24.535	-4.38 mg/L Standard Deviation 14.479	-0.47 mg/L Standard Deviation 27.932	-6.60 mg/L Standard Deviation 25.895	-6.36 mg/L Standard Deviation 22.571	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-4.21 mg/L Standard Deviation 27.424	-2.35 mg/L Standard Deviation 37.226	-2.73 mg/L Standard Deviation 21.272
Change From Baseline in hsCRP - Observed Data WK40,n=101,96,na,na,29,29,22,20,86,15,17	-4.73 mg/L Standard Deviation 13.502	-12.63 mg/L Standard Deviation 23.788	-2.75 mg/L Standard Deviation 17.297	-7.95 mg/L Standard Deviation 18.343	-8.74 mg/L Standard Deviation 22.257	-7.09 mg/L Standard Deviation 24.325	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-7.07 mg/L Standard Deviation 26.156	2.39 mg/L Standard Deviation 32.966	-4.46 mg/L Standard Deviation 22.808
Change From Baseline in hsCRP - Observed Data Wk44,n=97,92,na,na,,28,28,20,19,85,15,16	-7.27 mg/L Standard Deviation 13.887	-12.32 mg/L Standard Deviation 25.470	-1.33 mg/L Standard Deviation 4.846	-3.69 mg/L Standard Deviation 24.389	-6.59 mg/L Standard Deviation 20.975	-7.25 mg/L Standard Deviation 24.681	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-6.66 mg/L Standard Deviation 23.396	-8.53 mg/L Standard Deviation 19.970	-6.50 mg/L Standard Deviation 19.968
Change From Baseline in hsCRP - Observed Data Wk48,n=97,91,na,na,28,29,20,19,79,13,14	-6.97 mg/L Standard Deviation 13.680	-13.90 mg/L Standard Deviation 25.636	-3.50 mg/L Standard Deviation 21.343	-4.48 mg/L Standard Deviation 16.918	-6.19 mg/L Standard Deviation 18.912	-7.63 mg/L Standard Deviation 21.682	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-10.49 mg/L Standard Deviation 25.564	-4.76 mg/L Standard Deviation 15.784	-1.43 mg/L Standard Deviation 33.122
Change From Baseline in hsCRP - Observed Data Wk52,n=95,92,na,na,29,28,20,18,83,16,16	-4.88 mg/L Standard Deviation 11.707	-11.19 mg/L Standard Deviation 27.768	-6.73 mg/L Standard Deviation 14.972	-5.78 mg/L Standard Deviation 18.534	-6.68 mg/L Standard Deviation 26.240	-8.14 mg/L Standard Deviation 22.149	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mg/L Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-4.63 mg/L Standard Deviation 25.795	-4.79 mg/L Standard Deviation 22.882	2.95 mg/L Standard Deviation 9.880

SECONDARY outcome

Timeframe: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Population: Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and each post-baseline time point were analyzed for that post-baseline time point. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.

Blood samples were obtained to monitor disease activity and response to treatment. A negative change from baseline indicates improvement. The ESR results from baseline up to week 52 were based on observed data, i.e. without imputation.

Outcome measures

Measure	Placebo Responder - AIN457 150mg n=22 Participants Participants switched from placebo to AIN457 150 mg starting at week 24.	Abatacept Responders n=101 Participants Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).	Abatacept Non-responders - AIN457 75mg n=18 Participants Participants switched from placebo to AIN457 75 mg starting at week 24.	Abatacept Non-responders - AIN457 150mg n=19 Participants Participants switched from abatacept to AIN457 150 mg starting at week 24.	AIN457 10mg/kg - 75 mg n=138 Participants Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.	AIN457 10mg/kg - 150 mg n=137 Participants Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.	Placebo n=138 Participants Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=138 Participants Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).	Placebo Non-responder - AIN457 75 mg n=39 Participants Participants switched from placebo to AIN457 75 mg starting at week 16.	Placebo Non-responder - AIN457 150 mg n=39 Participants Participants switched from placebo to AIN457 150 mg starting at week 16.	Placebo Responder - AIN457 75mg n=23 Participants Participants switched from placebo to AIN457 75 mg starting at week 24.
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk1,n=133,130,131,131,39,36,21,22,97,17,17,	-7.1 mm/hr Standard Deviation 13.22	-10.2 mm/hr Standard Deviation 17.11	-7.7 mm/hr Standard Deviation 13.90	-7.2 mm/hr Standard Deviation 16.30	-7.5 mm/hr Standard Deviation 18.74	-8.4 mm/hr Standard Deviation 19.20	-5.7 mm/hr Standard Deviation 15.68	-9.5 mm/hr Standard Deviation 16.55	-8.4 mm/hr Standard Deviation 12.65	-1.1 mm/hr Standard Deviation 18.88	-5.7 mm/hr Standard Deviation 14.97
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk2,n=133,130,135,134,39,36,23,22,99,17,18	-6.6 mm/hr Standard Deviation 14.44	-10.2 mm/hr Standard Deviation 20.33	-12.5 mm/hr Standard Deviation 16.71	-13.6 mm/hr Standard Deviation 17.78	-12.2 mm/hr Standard Deviation 19.06	-10.5 mm/hr Standard Deviation 19.05	-5.7 mm/hr Standard Deviation 18.22	-11.0 mm/hr Standard Deviation 19.50	-4.0 mm/hr Standard Deviation 12.69	-5.6 mm/hr Standard Deviation 26.44	-9.7 mm/hr Standard Deviation 17.86
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk4,n=133,135,131,133,39,39,23,21,97,17,19	-8.2 mm/hr Standard Deviation 23.89	-12.3 mm/hr Standard Deviation 18.66	-15.8 mm/hr Standard Deviation 17.49	-11.3 mm/hr Standard Deviation 16.46	-12.7 mm/hr Standard Deviation 22.23	-12.1 mm/hr Standard Deviation 21.88	-6.0 mm/hr Standard Deviation 18.90	-12.6 mm/hr Standard Deviation 18.14	-3.7 mm/hr Standard Deviation 14.35	-3.8 mm/hr Standard Deviation 20.50	-9.3 mm/hr Standard Deviation 13.81
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk8,n=133,129,131,132,39,39,23,22,96,17,19	-8.3 mm/hr Standard Deviation 14.29	-18.3 mm/hr Standard Deviation 21.56	-13.9 mm/hr Standard Deviation 23.29	-17.6 mm/hr Standard Deviation 15.03	-15.4 mm/hr Standard Deviation 20.38	-15.7 mm/hr Standard Deviation 21.62	-6.4 mm/hr Standard Deviation 22.72	-17.6 mm/hr Standard Deviation 20.89	-9.4 mm/hr Standard Deviation 19.24	-0.9 mm/hr Standard Deviation 27.25	-8.2 mm/hr Standard Deviation 24.09
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk12,n=133,118,127,131,39,39,23,21,96,17,18	-5.5 mm/hr Standard Deviation 20.06	-19.9 mm/hr Standard Deviation 21.08	-18.4 mm/hr Standard Deviation 23.07	-17.9 mm/hr Standard Deviation 19.31	-14.7 mm/hr Standard Deviation 20.08	-18.4 mm/hr Standard Deviation 21.18	-5.8 mm/hr Standard Deviation 21.02	-19.4 mm/hr Standard Deviation 20.97	-5.9 mm/hr Standard Deviation 17.96	-1.5 mm/hr Standard Deviation 25.62	-11.2 mm/hr Standard Deviation 18.06
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk16,n=129,121,122,130,36,38,21,22,95,16,19	-4.9 mm/hr Standard Deviation 20.54	-21.1 mm/hr Standard Deviation 24.73	-14.9 mm/hr Standard Deviation 17.78	-8.8 mm/hr Standard Deviation 25.22	-16.2 mm/hr Standard Deviation 21.22	-15.6 mm/hr Standard Deviation 19.09	-6.5 mm/hr Standard Deviation 23.48	-18.5 mm/hr Standard Deviation 24.32	-3.1 mm/hr Standard Deviation 19.21	-1.1 mm/hr Standard Deviation 25.47	-17.6 mm/hr Standard Deviation 23.03
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk20,n=123,116,120,127,38,37,23,21,91,17,19	-11.6 mm/hr Standard Deviation 34.23	-7.0 mm/hr Standard Deviation 22.32	-22.0 mm/hr Standard Deviation 23.60	-20.5 mm/hr Standard Deviation 22.81	-16.3 mm/hr Standard Deviation 20.90	-17.7 mm/hr Standard Deviation 19.90	-9.1 mm/hr Standard Deviation 26.29	-21.1 mm/hr Standard Deviation 23.66	-21.1 mm/hr Standard Deviation 23.66	-10.5 mm/hr Standard Deviation 20.08	-7.4 mm/hr Standard Deviation 29.40
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk24,n=122,113,117,123,38,36,21,22,88,17,18	-5.5 mm/hr Standard Deviation 27.07	-21.1 mm/hr Standard Deviation 24.62	-20.7 mm/hr Standard Deviation 20.65	-11.4 mm/hr Standard Deviation 26.96	-13.9 mm/hr Standard Deviation 23.65	-16.0 mm/hr Standard Deviation 20.20	-12.0 mm/hr Standard Deviation 24.31	-19.6 mm/hr Standard Deviation 24.52	-10.8 mm/hr Standard Deviation 20.33	-14.7 mm/hr Standard Deviation 27.77	-16.1 mm/hr Standard Deviation 21.57
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk28,n=119,110,na,na,34,35,21,21,89,17,19	-14.6 mm/hr Standard Deviation 17.31	-22.4 mm/hr Standard Deviation 22.90	-26.1 mm/hr Standard Deviation 19.83	-17.4 mm/hr Standard Deviation 24.77	-15.4 mm/hr Standard Deviation 22.95	-16.8 mm/hr Standard Deviation 23.05	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-17.9 mm/hr Standard Deviation 24.87	-12.5 mm/hr Standard Deviation 30.87	-12.3 mm/hr Standard Deviation 24.10
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk32,n=108,101,na,na,34,32,21,21,88,17,16	-14.1 mm/hr Standard Deviation 20.72	-25.5 mm/hr Standard Deviation 24.89	-25.7 mm/hr Standard Deviation 21.14	-23.1 mm/hr Standard Deviation 21.46	-18.3 mm/hr Standard Deviation 23.51	-17.4 mm/hr Standard Deviation 21.57	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-17.2 mm/hr Standard Deviation 16.70	-12.8 mm/hr Standard Deviation 26.21	-16.8 mm/hr Standard Deviation 24.37
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk36,n=107,98,na,na,32,31,21,20,87,18,16	-16.5 mm/hr Standard Deviation 17.95	-21.7 mm/hr Standard Deviation 25.40	-26.0 mm/hr Standard Deviation 21.21	-16.6 mm/hr Standard Deviation 23.31	-16.6 mm/hr Standard Deviation 25.20	-18.4 mm/hr Standard Deviation 21.51	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-17.8 mm/hr Standard Deviation 21.72	-13.4 mm/hr Standard Deviation 29.49	-17.3 mm/hr Standard Deviation 22.02
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk40,n=101,96,na,na,29,29,22,20,85,15,17	-16.4 mm/hr Standard Deviation 21.79	-22.2 mm/hr Standard Deviation 26.24	-23.8 mm/hr Standard Deviation 22.96	-22.9 mm/hr Standard Deviation 15.57	-18.1 mm/hr Standard Deviation 21.06	-17.3 mm/hr Standard Deviation 21.05	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-20.6 mm/hr Standard Deviation 19.66	-12.3 mm/hr Standard Deviation 26.37	-13.3 mm/hr Standard Deviation 18.78
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk44,n=98,93,na,na,28,28,20,19,85,15,16	-19.2 mm/hr Standard Deviation 22.57	-24.9 mm/hr Standard Deviation 25.66	-22.3 mm/hr Standard Deviation 23.36	-18.5 mm/hr Standard Deviation 21.00	-18.0 mm/hr Standard Deviation 21.08	-16.7 mm/hr Standard Deviation 23.87	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-20.1 mm/hr Standard Deviation 17.61	-16.0 mm/hr Standard Deviation 25.30	-12.0 mm/hr Standard Deviation 29.20
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk48,n=97,92,na,na,28,30,20,19,79,13,14	-19.4 mm/hr Standard Deviation 20.58	-23.9 mm/hr Standard Deviation 25.56	-18.9 mm/hr Standard Deviation 26.41	-20.2 mm/hr Standard Deviation 18.16	-17.8 mm/hr Standard Deviation 23.11	-19.8 mm/hr Standard Deviation 20.30	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-20.8 mm/hr Standard Deviation 18.26	-7.2 mm/hr Standard Deviation 22.58	-12.2 mm/hr Standard Deviation 29.55
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data Wk52,n=94,91,na,na,29,28,20,18,83,16,16	-13.6 mm/hr Standard Deviation 27.16	-25.2 mm/hr Standard Deviation 27.88	-27.4 mm/hr Standard Deviation 22.71	-15.4 mm/hr Standard Deviation 22.53	-17.7 mm/hr Standard Deviation 21.08	-20.6 mm/hr Standard Deviation 23.48	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	NA mm/hr Standard Deviation NA After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.	-14.9 mm/hr Standard Deviation 20.53	-15.1 mm/hr Standard Deviation 21.50	-14.4 mm/hr Standard Deviation 24.54

Adverse Events

Any AIN457 75 mg

Serious events: 30 serious events

Other events: 144 other events

Deaths: 0 deaths

Any AIN457 150 mg

Serious events: 28 serious events

Other events: 146 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 51 other events

Deaths: 0 deaths

Abatacept

Serious events: 9 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Measure	Any AIN457 75 mg n=218 participants at risk Any AIN457 75 mg	Any AIN457 150 mg n=215 participants at risk Any AIN457 150 mg	Placebo n=139 participants at risk Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=137 participants at risk Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Blood and lymphatic system disorders Thrombocytopenia	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Cardiac disorders Angina pectoris	0.00% 0/218	0.00% 0/215	0.72% 1/139	0.00% 0/137
Cardiac disorders Angina unstable	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Cardiac disorders Cardiac failure	0.92% 2/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Cardiac disorders Mitral valve incompetence	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Cardiac disorders Palpitations	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Cardiac disorders Sinus tachycardia	0.00% 0/218	0.00% 0/215	0.72% 1/139	0.00% 0/137
Ear and labyrinth disorders Sudden hearing loss	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Eye disorders Cataract	0.00% 0/218	0.00% 0/215	0.72% 1/139	0.00% 0/137
Gastrointestinal disorders Abdominal pain	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Gastrointestinal disorders Colitis ischaemic	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Gastrointestinal disorders Inguinal hernia	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Gastrointestinal disorders Intestinal polyp	0.00% 0/218	0.00% 0/215	0.00% 0/139	0.73% 1/137
Gastrointestinal disorders Umbilical hernia	0.00% 0/218	0.00% 0/215	0.00% 0/139	0.73% 1/137
General disorders Cyst	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
General disorders Death	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
General disorders Device dislocation	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
General disorders General physical health deterioration	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Hepatobiliary disorders Bile duct stone	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Hepatobiliary disorders Cholelithiasis	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Hepatobiliary disorders Hepatic steatosis	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Hepatobiliary disorders Liver disorder	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Infections and infestations Cellulitis	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Infections and infestations Diverticulitis	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Infections and infestations Escherichia urinary tract infection	0.46% 1/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Infections and infestations Eye abscess	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Infections and infestations Gastroenteritis	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Infections and infestations Gastroenteritis salmonella	0.00% 0/218	0.00% 0/215	0.72% 1/139	0.00% 0/137
Infections and infestations H1N1 influenza	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Infections and infestations Herpes zoster oticus	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Infections and infestations Joint abscess	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Infections and infestations Lower respiratory tract infection	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Infections and infestations Meningitis bacterial	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Infections and infestations Pneumonia influenzal	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Infections and infestations Pyelonephritis acute	0.00% 0/218	0.00% 0/215	0.00% 0/139	0.73% 1/137
Infections and infestations Sepsis	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Infections and infestations Septic shock	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Infections and infestations Sinusitis	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Infections and infestations Tooth abscess	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Injury, poisoning and procedural complications Contusion	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Injury, poisoning and procedural complications Laceration	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Injury, poisoning and procedural complications Procedural headache	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Injury, poisoning and procedural complications Spinal fracture	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Musculoskeletal and connective tissue disorders Acquired claw toe	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Musculoskeletal and connective tissue disorders Arthritis	0.46% 1/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Musculoskeletal and connective tissue disorders Back pain	0.92% 2/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Musculoskeletal and connective tissue disorders Bursitis	0.46% 1/218	0.47% 1/215	0.72% 1/139	0.00% 0/137
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/218	0.93% 2/215	0.00% 0/139	0.00% 0/137
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/218	0.93% 2/215	0.00% 0/139	0.73% 1/137
Musculoskeletal and connective tissue disorders Osteoarthritis	1.8% 4/218	0.93% 2/215	0.00% 0/139	0.00% 0/137
Musculoskeletal and connective tissue disorders Osteoporotic fracture	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.73% 1/137
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/218	0.93% 2/215	0.00% 0/139	0.00% 0/137
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/218	0.00% 0/215	0.00% 0/139	0.73% 1/137
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroadenoma of breast	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.46% 1/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Nervous system disorders Cerebral ischaemia	0.00% 0/218	0.00% 0/215	0.00% 0/139	0.73% 1/137
Nervous system disorders Cerebrospinal fluid leakage	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Nervous system disorders Cerebrovascular accident	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Nervous system disorders Formication	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Nervous system disorders Lumbar radiculopathy	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Nervous system disorders Meningorrhagia	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Nervous system disorders Perineurial cyst	0.00% 0/218	0.00% 0/215	0.72% 1/139	0.00% 0/137
Nervous system disorders Syncope	0.00% 0/218	0.00% 0/215	0.00% 0/139	0.73% 1/137
Nervous system disorders Transient ischaemic attack	0.92% 2/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Nervous system disorders Vertebrobasilar insufficiency	0.00% 0/218	0.00% 0/215	0.72% 1/139	0.00% 0/137
Psychiatric disorders Delirium	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Psychiatric disorders Depression	0.00% 0/218	0.00% 0/215	0.72% 1/139	0.00% 0/137
Renal and urinary disorders Acute kidney injury	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.73% 1/137
Reproductive system and breast disorders Cystocele	0.00% 0/218	0.00% 0/215	0.00% 0/139	0.73% 1/137
Reproductive system and breast disorders Metrorrhagia	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Reproductive system and breast disorders Rectocele	0.00% 0/218	0.00% 0/215	0.00% 0/139	0.73% 1/137
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.46% 1/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Respiratory, thoracic and mediastinal disorders Hypoxia	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/218	0.00% 0/215	0.00% 0/139	0.73% 1/137
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Skin and subcutaneous tissue disorders Rash	0.00% 0/218	0.00% 0/215	0.00% 0/139	0.73% 1/137
Skin and subcutaneous tissue disorders Skin ulcer	0.46% 1/218	0.47% 1/215	0.00% 0/139	0.00% 0/137
Vascular disorders Venous thrombosis limb	0.46% 1/218	0.00% 0/215	0.00% 0/139	0.00% 0/137

Other adverse events

Measure	Any AIN457 75 mg n=218 participants at risk Any AIN457 75 mg	Any AIN457 150 mg n=215 participants at risk Any AIN457 150 mg	Placebo n=139 participants at risk Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.	Abatacept n=137 participants at risk Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Blood and lymphatic system disorders Anaemia	4.6% 10/218	4.7% 10/215	5.8% 8/139	4.4% 6/137
Blood and lymphatic system disorders Leukopenia	2.8% 6/218	1.9% 4/215	0.00% 0/139	1.5% 2/137
Blood and lymphatic system disorders Lymphopenia	2.3% 5/218	2.3% 5/215	2.9% 4/139	1.5% 2/137
Blood and lymphatic system disorders Neutrophilia	0.92% 2/218	0.93% 2/215	2.2% 3/139	0.73% 1/137
Blood and lymphatic system disorders Thrombocytopenia	0.46% 1/218	0.47% 1/215	2.9% 4/139	0.73% 1/137
Ear and labyrinth disorders Vertigo	0.46% 1/218	2.3% 5/215	0.00% 0/139	0.73% 1/137
Gastrointestinal disorders Diarrhoea	7.3% 16/218	5.6% 12/215	0.00% 0/139	6.6% 9/137
Gastrointestinal disorders Dyspepsia	2.8% 6/218	1.4% 3/215	0.72% 1/139	1.5% 2/137
Gastrointestinal disorders Nausea	4.1% 9/218	2.3% 5/215	1.4% 2/139	0.73% 1/137
General disorders Oedema peripheral	4.1% 9/218	2.8% 6/215	0.00% 0/139	1.5% 2/137
General disorders Pyrexia	1.4% 3/218	4.2% 9/215	0.72% 1/139	1.5% 2/137
Infections and infestations Bronchitis	4.6% 10/218	5.6% 12/215	0.00% 0/139	3.6% 5/137
Infections and infestations Gastroenteritis	3.7% 8/218	1.9% 4/215	0.00% 0/139	3.6% 5/137
Infections and infestations Influenza	3.2% 7/218	6.0% 13/215	0.72% 1/139	0.73% 1/137
Infections and infestations Nasopharyngitis	11.0% 24/218	7.9% 17/215	2.9% 4/139	5.8% 8/137
Infections and infestations Oral candidiasis	0.46% 1/218	1.4% 3/215	0.00% 0/139	2.9% 4/137
Infections and infestations Pharyngitis	4.6% 10/218	2.3% 5/215	0.72% 1/139	3.6% 5/137
Infections and infestations Respiratory tract infection	0.92% 2/218	2.3% 5/215	0.00% 0/139	0.73% 1/137
Infections and infestations Rhinitis	3.7% 8/218	5.6% 12/215	0.72% 1/139	2.2% 3/137
Infections and infestations Sinusitis	4.1% 9/218	3.3% 7/215	1.4% 2/139	0.73% 1/137
Infections and infestations Tonsillitis	2.8% 6/218	1.4% 3/215	0.00% 0/139	0.00% 0/137
Infections and infestations Tracheobronchitis	2.3% 5/218	0.47% 1/215	0.72% 1/139	0.73% 1/137
Infections and infestations Upper respiratory tract infection	8.3% 18/218	9.8% 21/215	6.5% 9/139	4.4% 6/137
Infections and infestations Urinary tract infection	7.3% 16/218	4.7% 10/215	1.4% 2/139	5.8% 8/137
Infections and infestations Viral infection	0.46% 1/218	2.8% 6/215	0.00% 0/139	1.5% 2/137
Injury, poisoning and procedural complications Contusion	0.92% 2/218	2.3% 5/215	0.72% 1/139	0.73% 1/137
Injury, poisoning and procedural complications Fall	1.4% 3/218	3.3% 7/215	2.2% 3/139	0.73% 1/137
Investigations Alanine aminotransferase increased	1.8% 4/218	1.4% 3/215	0.00% 0/139	2.2% 3/137
Investigations Lipoprotein (a) increased	0.92% 2/218	2.8% 6/215	0.00% 0/139	0.73% 1/137
Metabolism and nutrition disorders Dyslipidaemia	2.3% 5/218	1.4% 3/215	0.72% 1/139	1.5% 2/137
Metabolism and nutrition disorders Hypercholesterolaemia	3.2% 7/218	3.3% 7/215	4.3% 6/139	7.3% 10/137
Metabolism and nutrition disorders Hyperlipidaemia	2.8% 6/218	5.1% 11/215	1.4% 2/139	0.73% 1/137
Metabolism and nutrition disorders Hypertriglyceridaemia	0.92% 2/218	0.93% 2/215	2.2% 3/139	2.2% 3/137
Metabolism and nutrition disorders Hypocalcaemia	0.92% 2/218	1.4% 3/215	2.2% 3/139	0.73% 1/137
Musculoskeletal and connective tissue disorders Arthralgia	7.8% 17/218	7.0% 15/215	0.72% 1/139	3.6% 5/137
Musculoskeletal and connective tissue disorders Arthritis	2.3% 5/218	2.3% 5/215	1.4% 2/139	2.2% 3/137
Musculoskeletal and connective tissue disorders Back pain	5.5% 12/218	4.7% 10/215	1.4% 2/139	4.4% 6/137
Musculoskeletal and connective tissue disorders Bursitis	2.8% 6/218	2.3% 5/215	0.72% 1/139	0.00% 0/137
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.8% 4/218	3.3% 7/215	0.72% 1/139	0.00% 0/137
Musculoskeletal and connective tissue disorders Osteoarthritis	2.8% 6/218	1.9% 4/215	0.00% 0/139	1.5% 2/137
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	8.7% 19/218	10.2% 22/215	4.3% 6/139	4.4% 6/137
Musculoskeletal and connective tissue disorders Rheumatoid nodule	0.46% 1/218	2.3% 5/215	0.00% 0/139	0.00% 0/137
Nervous system disorders Dizziness	1.4% 3/218	0.93% 2/215	0.00% 0/139	2.2% 3/137
Nervous system disorders Headache	8.3% 18/218	5.1% 11/215	2.9% 4/139	6.6% 9/137
Nervous system disorders Paraesthesia	1.4% 3/218	2.3% 5/215	0.72% 1/139	0.73% 1/137
Psychiatric disorders Insomnia	1.4% 3/218	1.9% 4/215	0.00% 0/139	2.2% 3/137
Respiratory, thoracic and mediastinal disorders Cough	1.8% 4/218	2.3% 5/215	2.2% 3/139	2.9% 4/137
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.6% 10/218	2.3% 5/215	0.00% 0/139	0.73% 1/137
Skin and subcutaneous tissue disorders Alopecia	1.4% 3/218	2.3% 5/215	0.00% 0/139	0.00% 0/137
Skin and subcutaneous tissue disorders Dermatitis allergic	0.46% 1/218	0.00% 0/215	0.72% 1/139	2.2% 3/137
Skin and subcutaneous tissue disorders Rash	3.2% 7/218	1.9% 4/215	0.72% 1/139	2.2% 3/137
Vascular disorders Hypertension	9.2% 20/218	4.7% 10/215	2.9% 4/139	3.6% 5/137

Additional Information

Study Director

Novartis

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER