Trial Outcomes & Findings for Efficacy at 24 Weeks With Long Term Safety, Tolerability and Efficacy up to 5 Years of Secukinumab in Patients of Active Psoriatic Arthritis (NCT NCT01752634)

Last Updated: 2020-05-13

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). For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their ACR20 was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

397 participants

Primary outcome timeframe

Week 24

Results posted on

2020-05-13

Participant Flow

The study population was comprised of subjects who had passed screening assessments, complied with eligibility criteria and had provided written consent

At baseline, all eligible subjects were randomized via Interactive Response Technology (IRT) to one of the 4 treatment arms. At Week 16, Subjects on Placebo were rerandomized to receive secukinumab 150 mg s.c. or 300 mg s.c. from Week 16 (non-responder) or Week 24 (responder).

Participant milestones

Participant milestones
Measure	Secukinumab (AIN457) 75 mg s.c. Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 150 mg s.c. or 300 mg s.c	Secukinumab (AIN457) 150 mg s.c. Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Secukinumab (AIN457) 300 mg s.c. Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260.	Placebo - AIN457 150 mg Placebo - rerandomized to AIN457 150 mg starting at Week 16 (non-responder) or Week 24 (responder). After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Placebo - AIN457 300 mg Placebo - rerandomized to AIN457 300 mg starting at Week 16 (non-responder) or Week 24 (responder).	Placebo - Not Rerandomized Placebo - not rerandomized (subjects discontinued prior to rerandomization scheduled for week 16)
Up to Week 24 (Primary Analysis) STARTED	99	100	100	43	45	10
Up to Week 24 (Primary Analysis) COMPLETED	93	95	97	43	45	0
Up to Week 24 (Primary Analysis) NOT COMPLETED	6	5	3	0	0	10
Week 24 to Week 260 STARTED	93	95	97	43	45	0
Week 24 to Week 260 COMPLETED	59	65	64	29	31	0
Week 24 to Week 260 NOT COMPLETED	34	30	33	14	14	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Secukinumab (AIN457) 75 mg s.c. Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 150 mg s.c. or 300 mg s.c	Secukinumab (AIN457) 150 mg s.c. Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Secukinumab (AIN457) 300 mg s.c. Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260.	Placebo - AIN457 150 mg Placebo - rerandomized to AIN457 150 mg starting at Week 16 (non-responder) or Week 24 (responder). After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Placebo - AIN457 300 mg Placebo - rerandomized to AIN457 300 mg starting at Week 16 (non-responder) or Week 24 (responder).	Placebo - Not Rerandomized Placebo - not rerandomized (subjects discontinued prior to rerandomization scheduled for week 16)
Up to Week 24 (Primary Analysis) Subject/guardian decision	1	1	1	0	0	3
Up to Week 24 (Primary Analysis) Physician Decision	0	1	0	0	0	0
Up to Week 24 (Primary Analysis) Lack of Efficacy	2	3	0	0	0	3
Up to Week 24 (Primary Analysis) Adverse Event	3	0	2	0	0	4
Week 24 to Week 260 Lack of Efficacy	15	7	7	3	4	0
Week 24 to Week 260 Subject/guardian decision	12	10	9	5	5	0
Week 24 to Week 260 Physician Decision	1	2	4	2	1	0
Week 24 to Week 260 Death	0	1	0	0	0	0
Week 24 to Week 260 Pregnancy	0	0	1	0	0	0
Week 24 to Week 260 Noncompliance with study treatment	0	0	1	0	0	0
Week 24 to Week 260 Lost to Follow-up	2	2	3	0	2	0
Week 24 to Week 260 Adverse Event	4	8	8	4	2	0

Baseline Characteristics

Efficacy at 24 Weeks With Long Term Safety, Tolerability and Efficacy up to 5 Years of Secukinumab in Patients of Active Psoriatic Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Secukinumab (AIN457) 75 mg s.c. n=99 Participants Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 150 mg s.c. or 300 mg s.c	Secukinumab (AIN457) 150 mg s.c. n=100 Participants Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Secukinumab (AIN457) 300 mg s.c. n=100 Participants Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260.	Placebo - AIN457 150 mg n=43 Participants Placebo - rerandomized to AIN457 150 mg starting at Week 16 (non-responder) or Week 24 (responder). After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Placebo - AIN457 300 mg n=45 Participants Placebo - rerandomized to AIN457 300 mg starting at Week 16 (non-responder) or Week 24 (responder).	Placebo - Not Rerandomized n=10 Participants Placebo - not rerandomized (subjects discontinued prior to rerandomization scheduled for week 16)	Total n=397 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	0 Participants n=10 Participants	0 Participants n=115 Participants
Age, Categorical Between 18 and 65 years	93 Participants n=5 Participants	94 Participants n=7 Participants	90 Participants n=5 Participants	36 Participants n=4 Participants	43 Participants n=21 Participants	8 Participants n=10 Participants	364 Participants n=115 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants	7 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=10 Participants	33 Participants n=115 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	45 Participants n=7 Participants	49 Participants n=5 Participants	24 Participants n=4 Participants	29 Participants n=21 Participants	6 Participants n=10 Participants	205 Participants n=115 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	55 Participants n=7 Participants	51 Participants n=5 Participants	19 Participants n=4 Participants	16 Participants n=21 Participants	4 Participants n=10 Participants	192 Participants n=115 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	14 Participants n=115 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Race (NIH/OMB) White	90 Participants n=5 Participants	90 Participants n=7 Participants	96 Participants n=5 Participants	42 Participants n=4 Participants	43 Participants n=21 Participants	9 Participants n=10 Participants	370 Participants n=115 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants	7 Participants n=115 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Full Analysis Set.

Outcome measures

Outcome measures
Measure	Secukinumab (AIN457) 75 mg s.c. n=99 Participants Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 150 mg s.c. or 300 mg s.c	Secukinumab (AIN457) 150 mg s.c. n=100 Participants Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Secukinumab (AIN457) 300 mg s.c. n=100 Participants Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260.	Placebo s.c. n=98 Participants Placebo at BSL, Weeks 1, 2, 3 and 4, followed by placebo dosing every four weeks starting at Week 4 until up to Week 12 (non-responder) or Week 20 (responder) followed by re-randomization to AIN 150 mg s.c. or AIN 300 mg s.c. (starting from Week 16 or 24). After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients re-randomized to 150 mg s.c. could be changed to 300 mg s.c. Treatment could continue up to Week 260.
Number of Participants Achieving American College of Rheumatology 20 (ACR20) Response Criteria	29 Participants	51 Participants	54 Participants	15 Participants

SECONDARY outcome

Timeframe: Week 24

Population: Psoriasis Subset (≥3% skin involvement with psoriasis at baseline)

PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area \* area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 75 response was defined as participants achieving \>= 75% improvement from baseline. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their value was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias.

Outcome measures

Outcome measures
Measure	Secukinumab (AIN457) 75 mg s.c. n=50 Participants Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 150 mg s.c. or 300 mg s.c	Secukinumab (AIN457) 150 mg s.c. n=58 Participants Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Secukinumab (AIN457) 300 mg s.c. n=41 Participants Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260.	Placebo s.c. n=43 Participants Placebo at BSL, Weeks 1, 2, 3 and 4, followed by placebo dosing every four weeks starting at Week 4 until up to Week 12 (non-responder) or Week 20 (responder) followed by re-randomization to AIN 150 mg s.c. or AIN 300 mg s.c. (starting from Week 16 or 24). After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients re-randomized to 150 mg s.c. could be changed to 300 mg s.c. Treatment could continue up to Week 260.
Number of Participants Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis	14 Participants	28 Participants	26 Participants	7 Participants

SECONDARY outcome

Timeframe: Week 24

Population: Psoriasis Subset (≥3% skin involvement with psoriasis at baseline)

PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area \* area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 90 response was defined as participants achieving \>= 90% improvement from baseline. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their value was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias.

Outcome measures

Outcome measures
Measure	Secukinumab (AIN457) 75 mg s.c. n=50 Participants Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 150 mg s.c. or 300 mg s.c	Secukinumab (AIN457) 150 mg s.c. n=58 Participants Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Secukinumab (AIN457) 300 mg s.c. n=41 Participants Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260.	Placebo s.c. n=43 Participants Placebo at BSL, Weeks 1, 2, 3 and 4, followed by placebo dosing every four weeks starting at Week 4 until up to Week 12 (non-responder) or Week 20 (responder) followed by re-randomization to AIN 150 mg s.c. or AIN 300 mg s.c. (starting from Week 16 or 24). After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients re-randomized to 150 mg s.c. could be changed to 300 mg s.c. Treatment could continue up to Week 260.
Number of Participants Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis	6 Participants	19 Participants	20 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set, including only participants with measurements at baseline and Week 24. Participants in the Placebo arm who switched to Secukinumab prior to Week 24 were treated as missing.

The DAS28 is a measure of disease activity based on Swollen and Tender Joint Counts, ESR or CRP and the Patient Global Assessment. A DAS28 score \> 5.1 implies active disease, ≤ 3.2 low disease activity, and \< 2.6 remission. The score can range from 0 - 9.4. The data collected after the patient switched to secukinumab were treated as missing for placebo patients and were analyzed using a mixed-effects repeated measures model. For secukinumab patients, the actual values were used in the analysis. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Outcome measures

Outcome measures
Measure	Secukinumab (AIN457) 75 mg s.c. n=87 Participants Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 150 mg s.c. or 300 mg s.c	Secukinumab (AIN457) 150 mg s.c. n=91 Participants Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Secukinumab (AIN457) 300 mg s.c. n=93 Participants Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260.	Placebo s.c. n=32 Participants Placebo at BSL, Weeks 1, 2, 3 and 4, followed by placebo dosing every four weeks starting at Week 4 until up to Week 12 (non-responder) or Week 20 (responder) followed by re-randomization to AIN 150 mg s.c. or AIN 300 mg s.c. (starting from Week 16 or 24). After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients re-randomized to 150 mg s.c. could be changed to 300 mg s.c. Treatment could continue up to Week 260.
Change From Baseline in DAS28-CRP	-1.12 score on a scale Standard Error 0.111	-1.58 score on a scale Standard Error 0.109	-1.61 score on a scale Standard Error 0.110	-0.96 score on a scale Standard Error 0.149

SECONDARY outcome

Timeframe: Baseline, Week 24

The SF-36 is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions. Score range is from 0 (no problems) to 100 (unable to perform the activity). SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the Physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS was used. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Outcome measures

Outcome measures
Measure	Secukinumab (AIN457) 75 mg s.c. n=91 Participants Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 150 mg s.c. or 300 mg s.c	Secukinumab (AIN457) 150 mg s.c. n=96 Participants Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Secukinumab (AIN457) 300 mg s.c. n=96 Participants Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260.	Placebo s.c. n=33 Participants Placebo at BSL, Weeks 1, 2, 3 and 4, followed by placebo dosing every four weeks starting at Week 4 until up to Week 12 (non-responder) or Week 20 (responder) followed by re-randomization to AIN 150 mg s.c. or AIN 300 mg s.c. (starting from Week 16 or 24). After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients re-randomized to 150 mg s.c. could be changed to 300 mg s.c. Treatment could continue up to Week 260.
Change From Baseline in SF36-Physical Component Score	4.38 Score on a scale Standard Error 0.750	6.39 Score on a scale Standard Error 0.734	7.25 Score on a scale Standard Error 0.740	1.95 Score on a scale Standard Error 0.974

SECONDARY outcome

Timeframe: Baseline, Week 24

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 Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Outcome measures

Outcome measures
Measure	Secukinumab (AIN457) 75 mg s.c. n=89 Participants Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 150 mg s.c. or 300 mg s.c	Secukinumab (AIN457) 150 mg s.c. n=95 Participants Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Secukinumab (AIN457) 300 mg s.c. n=95 Participants Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260.	Placebo s.c. n=33 Participants Placebo at BSL, Weeks 1, 2, 3 and 4, followed by placebo dosing every four weeks starting at Week 4 until up to Week 12 (non-responder) or Week 20 (responder) followed by re-randomization to AIN 150 mg s.c. or AIN 300 mg s.c. (starting from Week 16 or 24). After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients re-randomized to 150 mg s.c. could be changed to 300 mg s.c. Treatment could continue up to Week 260.
Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)	-0.32 Scores on a scale Standard Error 0.050	-0.48 Scores on a scale Standard Error 0.049	-0.56 Scores on a scale Standard Error 0.050	-0.31 Scores on a scale Standard Error 0.060

SECONDARY outcome

Timeframe: Week 24

Population: Full Analysis Set

ACR20 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). For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their ACR20 was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Outcome measures

Outcome measures
Measure	Secukinumab (AIN457) 75 mg s.c. n=99 Participants Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 150 mg s.c. or 300 mg s.c	Secukinumab (AIN457) 150 mg s.c. n=100 Participants Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Secukinumab (AIN457) 300 mg s.c. n=100 Participants Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260.	Placebo s.c. n=98 Participants Placebo at BSL, Weeks 1, 2, 3 and 4, followed by placebo dosing every four weeks starting at Week 4 until up to Week 12 (non-responder) or Week 20 (responder) followed by re-randomization to AIN 150 mg s.c. or AIN 300 mg s.c. (starting from Week 16 or 24). After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients re-randomized to 150 mg s.c. could be changed to 300 mg s.c. Treatment could continue up to Week 260.
Number of Participants Achieving American College of Rheumatology 50 (ACR50) Response Criteria	18 Participants	35 Participants	35 Participants	7 Participants

SECONDARY outcome

Timeframe: Week 24

Population: Dactylitis Subset (participants with dactylitis at baseline)

Resolution of dactylitis was evaluated in the subset of patients who had disease activity at baseline. In this analysis, a lower percentage is desirable and resolution is defined as complete absence of the symptom. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their assessment was set to nonresponse at Week 24 (presence of dactylitis). This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Outcome measures

Outcome measures
Measure	Secukinumab (AIN457) 75 mg s.c. n=33 Participants Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 150 mg s.c. or 300 mg s.c	Secukinumab (AIN457) 150 mg s.c. n=32 Participants Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Secukinumab (AIN457) 300 mg s.c. n=46 Participants Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260.	Placebo s.c. n=27 Participants Placebo at BSL, Weeks 1, 2, 3 and 4, followed by placebo dosing every four weeks starting at Week 4 until up to Week 12 (non-responder) or Week 20 (responder) followed by re-randomization to AIN 150 mg s.c. or AIN 300 mg s.c. (starting from Week 16 or 24). After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients re-randomized to 150 mg s.c. could be changed to 300 mg s.c. Treatment could continue up to Week 260.
Number of Participants With Dactylitis in the Subset of Subjects Who Had Dactylitis at Baseline	23 Participants	16 Participants	20 Participants	23 Participants

SECONDARY outcome

Timeframe: Week 24

Population: Enthesitis Subset (participants with enthesitis at baseline)

Resolution of enthesitis was evaluated in the subset of patients who had disease activity at baseline. In this analysis, a lower percentage is desirable and resolution is defined as complete absence of the symptom. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their assessment was set to nonresponse at Week 24 (presence of enthesitis). This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.

Outcome measures

Outcome measures
Measure	Secukinumab (AIN457) 75 mg s.c. n=68 Participants Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 150 mg s.c. or 300 mg s.c	Secukinumab (AIN457) 150 mg s.c. n=64 Participants Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260. After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients could be changed to 300 mg s.c	Secukinumab (AIN457) 300 mg s.c. n=56 Participants Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4 until up to Week 260.	Placebo s.c. n=65 Participants Placebo at BSL, Weeks 1, 2, 3 and 4, followed by placebo dosing every four weeks starting at Week 4 until up to Week 12 (non-responder) or Week 20 (responder) followed by re-randomization to AIN 150 mg s.c. or AIN 300 mg s.c. (starting from Week 16 or 24). After a protocol amendment (introduced in open label phase \> 2 years post randomization) patients re-randomized to 150 mg s.c. could be changed to 300 mg s.c. Treatment could continue up to Week 260.
Number of Participants With Enthesitis in the Subset of Subjects Who Had Enthesitis at Baseline	46 Participants	37 Participants	29 Participants	51 Participants

Adverse Events

Any AIN457 75 mg

Serious events: 17 serious events

Other events: 63 other events

Deaths: 0 deaths

Any AIN457 150 mg

Serious events: 28 serious events

Other events: 132 other events

Deaths: 1 deaths

Any AIN457 300 mg

Serious events: 42 serious events

Other events: 171 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

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 (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER