Study to Evaluate the Safety and Efficacy of Secukinumab 300 mg and 150 mg in Adult Patients With Active Psoriatic Arthritis (PsA) After 16 Weeks of Treatment Compared to Placebo

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02798211
• Collaborator: (none)
• Enrollment: 258
• Locations: 58
• Arms: 3
• Actual Duration (Months): 29.3
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To demonstrate that the efficacy of secukinumab 300 mg at Week 16 was superior to placebo in adult patients with active PsA based on the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response.

Condition or Disease	Intervention/Treatment	Phase
Psoriatic Arthritis	Drug: Secukinumab 300 mg; Drug: Secukinumab 150 mg; Other: Placebo	Phase 4

Detailed Description

Treatment Period 1 was defined as the period from Randomization through Week 16 (prior to the Week 16 dose). At the start of placebo-controlled Treatment Period 1, patients were randomized via Interactive Response Technology (IRT) in a 2:2:1 ratio to 1 of 3 treatment groups.

Group 1- Secukinumab 300 mg: secukinumab 300 mg (2 s.c. injections of the 150-mg dose) once weekly for 5 weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every 4 weeks.

Group 2- Secukinumab 150 mg: secukinumab 150 mg (1 s.c. injection of the 150-mg dose and 1 s.c. injection of placebo) once weekly for 5 weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every 4 weeks.

Group 3- Placebo: placebo (2 s.c. injections of 150 mg secukinumab placebo per dose) once per week for 5 weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every 4 weeks.

At each study treatment visit 2 s.c. injections in the form of prefilled syringes (PFS) were administered. This was necessary to maintain the blind, as secukinumab in PFS is available in either 1.0 mL (150 mg) or 2 x 1.0 mL (300 mg). Placebo to secukinumab was also available in 1.0 mL to match the active drug.

Rescue medication was not allowed before completion of Week 16 assessments.

Treatment Period 2 patients receiving secukinumab 300 mg (Group 1) continued to receive the same dose up to Week 48.

At Weeks 16, 28, and 40 patients on secukinumab 150 mg (Group 2) were classified as responders (≥20% improvement from BL in both tender and swollen joint counts) or nonresponders.

• At Weeks 16, 28, and 40 patients on secukinumab 150 mg (Group 2) who were responders continued to receive secukinumab 150 mg (1.0 mL) plus placebo (1.0 mL) every 4 weeks until next evaluation of responder status at Weeks 28 or 40.

• Patients who did not meet the responder criteria at Week 16, 28, or 40 started receiving secukinumab 300 mg s.c. every 4 weeks and continued this dose up to Week 48.

• Patients on placebo (Group 3) regardless of their responder status started receiving secukinumab 300 mg s.c. every 4 weeks from Week 16 up to Week 48.

Study Design

• Study Type: Interventional
• Actual Enrollment: 258 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Study design displays results combined as two or more Arms/Groups. Patients assigned to Placebo arm in Treatment Period 1 (TP1) may have switched to Secukinumab 300mg in Treatment Period 2 (TP2). Summaries by group were performed cumulatively by actual treatment received (as follows) for every visit until Week 16 groups in Treatment Period 1: · Secukinumab 300mg (Group 1) · Secukinumab 150mg (Group 2) · Placebo (Group 3) For entire treatment period, summaries by treatment group were performed cumulatively by the actual treatment received (as follows) for every visit til Week 52, including patients who switched at Weeks 16, 28, 40. For safety variables · Any Secukinumab 150 mg (Group 2) · Any Secukinumab 300mg (Group 1) · Any Secukinumab (Group 3) Hence, participants who received "Placebo" in TP1 were combined with participants who received "Any Secukinumab" in "Group 3" and "Any Secukinumab 300mg" in "Group 1" in TP2. Safety is presented for the ENTIRE period, including TP1 and TP2Study design displays results combined as two or more Arms/Groups. Patients assigned to Placebo arm in Treatment Period 1 (TP1) may have switched to Secukinumab 300mg in Treatment Period 2 (TP2). Summaries by group were performed cumulatively by actual treatment received (as follows) for every visit until Week 16 groups in Treatment Period 1: · Secukinumab 300mg (Group 1) · Secukinumab 150mg (Group 2) · Placebo (Group 3) For entire treatment period, summaries by treatment group were performed cumulatively by the actual treatment received (as follows) for every visit til Week 52, including patients who switched at Weeks 16, 28, 40. For safety variables · Any Secukinumab 150 mg (Group 2) · Any Secukinumab 300mg (Group 1) · Any Secukinumab (Group 3) Hence, participants who received "Placebo" in TP1 were combined with participants who received "Any Secukinumab" in "Group 3" and "Any Secukinumab 300mg" in "Group 1" in TP2. Safety is presented for the ENTIRE period, including TP1 and TP2
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Secukinumab 300 mg and 150 mg in Adult Patients With Active Psoriatic Arthritis After 16 Weeks of Treatment Compared to Placebo and to Assess the Safety, Tolerability and Efficacy up to 52 Weeks
• Actual Study Start Date: Jun 27, 2016
• Actual Primary Completion Date: Dec 5, 2018
• Actual Study Completion Date: Dec 5, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group 1 secukinumab 300mg s.c. injection	Drug: Secukinumab 300 mg; 150 mg x 2 s.c. injection; Other Names: AIN457
Active Comparator: Group 2 secukinumab 150 mg s.c. injection	Drug: Secukinumab 150 mg; 150 mg s.c. injection; Other Names: AIN457
Placebo Comparator: Group 3 Placebo s.c. injection	Other: Placebo; Placebo; Other Names: s.c. injection

Outcome Measures

Primary Outcome Measures

1. Percent of Patients Achieving American College of Rheumatology Score of at Least 20% (ACR20) Response Criteria on Secukinumab 300 mg and 150 mg vs. Placebo at Week 16 [16 Weeks]

   A patient was considered as improved according to the ACR20 criteria if she/he had at least 20% improvement in two of the following measures:Tender joint count, Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity, Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR). Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.

Secondary Outcome Measures

1. Percentage of Patients With Dactylitis in the Subset of Subjects Who Have Dactylitis at Week 16 [Week 16]

   The percent of patients in the Dactylitis Subset with dactylitis in the secukinumab 300 mg group at Week 16. Dactylitis is severe inflammation of the finger and toe joints. Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.

2. Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Baseline (SPARCC) at Week 16 [16 Weeks]

   Enthesitis, also called enthesopathy, is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.

3. Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Week 16 (LEI) [16 Weeks]

   Enthesitis, also called enthesopathy, is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. LEI=Leeds Enthesitis Index

4. Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Week 16 (Combined SPARCC and LEI) [16 Weeks]

   Statistical analysis (logistic regression) of presence of enthesitis (Combined SPARCC and LEI) by visit - in treatment period 1 (non-responder imputation) (Combined SPARCC and LEI Subset) Enthesitis, also called enthesopathy, is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.

5. Percentage of Patients Achieving ACR50 Response Criteria on Secukinumab 300 or 150 mg vs. Placebo at Week 16 [16 Weeks]

   A patient was considered as improved according the ACR50 criteria if she/he had at least 50% improvement in the two of the following measures: Tender joint count, Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity,Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR) Statistical analysis (logistic regression) of ACR50 response by visit - in treatment period 1 (non-responder imputation) (Full Analysis Set) Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.

6. Percentage of Patients Achieving ACR70 Response Criteria on Secukinumab 300 or 150 mg vs. Placebo at Week 16 [16 Weeks]

   A patient was considered as improved according the ACR70 criteria if she/he had at least 70% improvement in the two of the following measures: Tender joint count, Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity,Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR) Statistical analysis (logistic regression) of ACR70 response by visit - in treatment period 1 (non-responder imputation) Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.

7. Percentage of Patients Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Week 16 [16 Weeks]

   A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis.

8. Percentage of Patients Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Week 16 [16 Weeks]

   A 90% reduction in the Psoriasis Area and Severity Index score (PASI 90) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis.

9. Percentage of Patients Achieving a PASI100 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Week 16 [16 Weeks]

   A 100% reduction in the Psoriasis Area and Severity Index score (PASI 100) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis. Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.

10. Change From Baseline to Week 16 in DAS28-CRP [baseline, 16 weeks]

    DAS-CRP uses the C-Reactive Protein (CRP) value. Disease Activity Score (DAS28-CRP) values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28-CRP below the value of 2.6 is interpreted as Remission. DAS28-CRP uses 28 different joints for its calculation: proximal interphalangeal joints (10 joints) metacarpophalangeal joints (10) wrists (2) elbows (2) shoulders (2) knees (2) With the above mentioned parameters. Least squares mean (LSM), Least squares mean (LSM) treatment difference, 95% confidence interval (CI) for treatment difference, and p-values are from an analysis of covariance (ANCOVA) model with treatment (3 treatment groups), baseline DAS28-CRP score, methotrexate usage at baseline (yes, no), and body weight(kg) as explanatory variables.

11. Change From Baseline to Week 16 in HAQ-DI [16 Weeks]

    The Health assessment questionnaire disability index (HAQ-DI) is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area). The average score across the functional areas yields an overall HAQ score which ranges from 0 (no disability) to 3 (completely disabled).

Other Outcome Measures

1. Number and Percentage of Patients With ACR20 Response by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation) [up to 52 weeks]

   Exploratory The ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP)

2. Number and Percentage of Patients With ACR50, ACR70 Response by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation) [up to 52 weeks]

   Exploratory

3. Number and Percentage of Patients With Presence of Dactylitis by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation) [up to 52 weeks]

   Exploratory

4. Number and Percentage of Patients With Presence of Enthesitis by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation) [up to 52 weeks]

   Exploratory

5. Number and Percentage of Patients With Minimal Disease Activity Response by Visit in Entire Treatment Period (up to Week 52) (Non-responder Imputation) [up to 52 weeks]

   Exploratory

6. Number and Percentage of Patients With PASI75, PASI90 and PASI100 Response by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation) [up to 52 weeks]

   Exploratory

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or non-pregnant, non-lactating female patients at least 18 years of age

• Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months with moderate to severe PsA who must have at Baseline ≥3 tender joints out of 78 and ≥3 swollen out of 76 (dactylitis of a digit counts as one joint each)

• Rheumatoid factor and/or anti-CCP antibodies negative at screening

• A target skin psoriatic lesion and a PASI score of 1 or greater

Exclusion Criteria:

• Chest X-ray with evidence of ongoing infectious or malignant process

• Patients who ever received biologic immunomodulating agents including those targeting TNFα, IL-6 and IL-12/23 investigational or approved

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35205
2	Novartis Investigative Site	Little Rock	Arkansas	United States	72205
3	Novartis Investigative Site	El Cajon	California	United States	92020
4	Novartis Investigative Site	Fountain Valley	California	United States	92708
5	Novartis Investigative Site	La Jolla	California	United States	92093
6	Novartis Investigative Site	La Mesa	California	United States	91942
7	Novartis Investigative Site	Upland	California	United States	91786
8	Novartis Investigative Site	Aventura	Florida	United States	33180
9	Novartis Investigative Site	Clearwater	Florida	United States	33765
10	Novartis Investigative Site	DeBary	Florida	United States	32713
11	Novartis Investigative Site	Jacksonville	Florida	United States	32207
12	Novartis Investigative Site	North Naples	Florida	United States	34102
13	Novartis Investigative Site	Palm Harbor	Florida	United States	34684
14	Novartis Investigative Site	Pensacola	Florida	United States	32514
15	Novartis Investigative Site	Plantation	Florida	United States	33324
16	Novartis Investigative Site	Sarasota	Florida	United States	34239
17	Novartis Investigative Site	Tampa	Florida	United States	33609
18	Novartis Investigative Site	Tampa	Florida	United States	33613
19	Novartis Investigative Site	Duluth	Georgia	United States	30096
20	Novartis Investigative Site	Baltimore	Maryland	United States	21224
21	Novartis Investigative Site	Boston	Massachusetts	United States	02115
22	Novartis Investigative Site	Worcester	Massachusetts	United States	01655
23	Novartis Investigative Site	Battle Creek	Michigan	United States	49015
24	Novartis Investigative Site	Kalamazoo	Michigan	United States	49008
25	Novartis Investigative Site	Eagan	Minnesota	United States	55121
26	Novartis Investigative Site	Lincoln	Nebraska	United States	68516
27	Novartis Investigative Site	Las Vegas	Nevada	United States	89106
28	Novartis Investigative Site	Ridgewood	New Jersey	United States	07450
29	Novartis Investigative Site	Summit	New Jersey	United States	07901
30	Novartis Investigative Site	Albany	New York	United States	12206
31	Novartis Investigative Site	Brooklyn	New York	United States	11201
32	Novartis Investigative Site	Lake Success	New York	United States	11402
33	Novartis Investigative Site	Orchard Park	New York	United States	14127
34	Novartis Investigative Site	Potsdam	New York	United States	13676
35	Novartis Investigative Site	Saranac Lake	New York	United States	12983
36	Novartis Investigative Site	Charlotte	North Carolina	United States	28226
37	Novartis Investigative Site	Greensboro	North Carolina	United States	27408
38	Novartis Investigative Site	New Bern	North Carolina	United States	28562
39	Novartis Investigative Site	Marion	Ohio	United States	43302
40	Novartis Investigative Site	Perrysburg	Ohio	United States	43551
41	Novartis Investigative Site	Duncansville	Pennsylvania	United States	16635
42	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19104
43	Novartis Investigative Site	Charleston	South Carolina	United States	29460
44	Novartis Investigative Site	Greenville	South Carolina	United States	29601
45	Novartis Investigative Site	Orangeburg	South Carolina	United States	29118-2475
46	Novartis Investigative Site	Jackson	Tennessee	United States	38305
47	Novartis Investigative Site	Arlington	Texas	United States	76014
48	Novartis Investigative Site	Arlington	Texas	United States	77373
49	Novartis Investigative Site	Austin	Texas	United States	78731
50	Novartis Investigative Site	Dallas	Texas	United States	75231
51	Novartis Investigative Site	Dallas	Texas	United States	75246
52	Novartis Investigative Site	Houston	Texas	United States	77074
53	Novartis Investigative Site	Mesquite	Texas	United States	75150
54	Novartis Investigative Site	San Antonio	Texas	United States	78229
55	Novartis Investigative Site	Salt Lake City	Utah	United States	84132
56	Novartis Investigative Site	Seattle	Washington	United States	98122
57	Novartis Investigative Site	Spokane	Washington	United States	99204
58	Novartis Investigative Site	Santurce		Puerto Rico	00909

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Dec 12, 2016
• Statistical Analysis Plan - Dec 31, 2018

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02798211
• Other Study ID Numbers: CAIN457FUS01
• First Posted: Jun 14, 2016
• Last Update Posted: Oct 7, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: PsA; ACR; CASPAR; inflammatory arthritis; spondylitis
• Additional relevant MeSH terms: Arthritis; Arthritis, Psoriatic; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	Of 349 patients screened for the study, 271 passed screening and 258 were randomized (103 to secukinumab 300 mg, 103 to secukinumab 150 mg, and 52 to placebo). A higher percentage of patients in the secukinumab 300 mg group completed Period 1 (94.2%) than in the secukinumab 150 mg (90.3%) or placebo (88.5%) groups.
Pre-assignment Detail	This was a 2-Period study in which participants were randomized to one of three treatment groups (i.e., "secukinumab 300mg s.c. injection", "secukinumab 1500mg s.c. injection" and "placebo s.c. injection") in Period 1 and then some participants switched to Arms/Groups "Group 4", "Group 5", and "Group 6", in Period 2.

Arm/Group Title	Group 1	Group 2	Group 3	Group 4	Group 5	Group 6
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection	Secukinumab 150 mg - 150 mg (R)	Secukinumab 150 mg - 300 mg (NR)	Placebo - Secukinumab 300 mg
Period Title: Period 1
STARTED	103	103	52	0	0	0
COMPLETED	97	93	46	0	0	0
NOT COMPLETED	6	10	6	0	0	0
Period Title: Period 1
STARTED	97	0	0	50	42	46
COMPLETED	83	0	0	43	34	40
NOT COMPLETED	14	0	0	7	8	6

Baseline Characteristics

Arm/Group Title	Group 1	Group 2	Group 3	Total
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection	Total of all reporting groups
Overall Participants	103	103	52	258
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.9 (12.56)	51.3 (14.58)	53.1 (12.67)	52.2 (80.86)
Age, Customized (Count of Participants)
≥18-<40	20 19.4%	20 19.4%	8 15.4%	48 18.6%
≥40-<65	65 63.1%	61 59.2%	35 67.3%	161 62.4%
≥65-<75	14 13.6%	18 17.5%	9 17.3%	41 15.9%
≥75	4 3.9%	4 3.9%	0 0%	8 3.1%
Sex: Female, Male (Count of Participants)
Female	50 48.5%	47 45.6%	29 55.8%	126 48.8%
Male	53 51.5%	56 54.4%	23 44.2%	132 51.2%
Race/Ethnicity, Customized (Count of Participants)
Asian	9 8.7%	10 9.7%	1 1.9%	20 7.8%
Black	2 1.9%	2 1.9%	3 5.8%	7 2.7%
Caucasian	88 85.4%	88 85.4%	45 86.5%	221 85.7%
Native American	0 0%	1 1%	1 1.9%	2 0.8%
Other	2 1.9%	0 0%	2 3.8%	4 1.6%
Pacific Islander	1 1%	1 1%	0 0%	2 0.8%
Unknown	1 1%	1 1%	0 0%	2 0.8%

Outcome Measures

1. Primary Outcome

Title	Percent of Patients Achieving American College of Rheumatology Score of at Least 20% (ACR20) Response Criteria on Secukinumab 300 mg and 150 mg vs. Placebo at Week 16
Description	A patient was considered as improved according to the ACR20 criteria if she/he had at least 20% improvement in two of the following measures:Tender joint count, Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity, Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR). Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) includes all patients assigned study medication. Patients inappropriately randomized (e.g., IRT was called in error for randomization of a screen failed patient) were excluded from analysis set. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned at randomization.

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection
Measure Participants	103	103	52
Number [percentage of participants]	51.46 50%	36.89 35.8%	23.08 44.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1, Group 2
	Comments	secukinumab 300mg s.c. injection, 16 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of ACR20 response in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.51
	Confidence Interval	(2-Sided) 95%; 1.65 to 7.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2
	Comments	secukinumab 150 mg s.c. injection, 16 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0961
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of ACR20 response in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.92
	Confidence Interval	(2-Sided) 95%; 0.89 to 4.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Patients With Dactylitis in the Subset of Subjects Who Have Dactylitis at Week 16
Description	The percent of patients in the Dactylitis Subset with dactylitis in the secukinumab 300 mg group at Week 16. Dactylitis is severe inflammation of the finger and toe joints. Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Dactylitis Subset: The Dactylitis Subset comprises patients who have LDI >= 1 at baseline

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection
Measure Participants	49	52	23
Number [percent of participants]	53.06 51.5%	44.23 42.9%	65.22 125.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1
	Comments	secukinumab 300 mg s.c. injection, 16 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3330
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of presence of dactylitis by visit in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.22 to 1.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2
	Comments	secukinumab 150 mg s.c. injection, 16 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0841
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of presence of dactylitis in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.40
	Confidence Interval	(2-Sided) 95%; 0.14 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Baseline (SPARCC) at Week 16
Description	Enthesitis, also called enthesopathy, is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC) subset. The SPARCC Subset is comprised of patients who have SPARCC >= 1 at baseline. Score range is 0-16 sites where a higher indicates more enthesitis.

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection
Measure Participants	72	76	39
Number [percentage of participants]	63.89 62%	57.89 56.2%	76.92 147.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1
	Comments	secukinumab 300mg s.c. injection, 16 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1618
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of presence of enthesitis (SPARCC) in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; 0.21 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2
	Comments	secukinumab 150mg s.c. injection, 16 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0898
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of presence of enthesitis (SPARCC) in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; 0.19 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Week 16 (LEI)
Description	Enthesitis, also called enthesopathy, is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. LEI=Leeds Enthesitis Index
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

LEI subset: The LEI Subset comprises patients who have LEI >= 1 at baseline. LEI uses 6 sites for evaluation of enthesitis, so the range is 0-6 withy a higher number indicating more arthritis.

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection
Measure Participants	66	67	34
Number [percentage of participants]	56.06 54.4%	52.24 50.7%	82.35 158.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1
	Comments	secukinumab 300mg s.c. injection, 16 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0125
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of presence of enthesitis (LEI) in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.27
	Confidence Interval	(2-Sided) 95%; 0.09 to 0.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2
	Comments	secukinumab 150mg s.c. injection, 16 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0086
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of presence of enthesitis (SPARCC) in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 95%; 0.09 to 0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Week 16 (Combined SPARCC and LEI)
Description	Statistical analysis (logistic regression) of presence of enthesitis (Combined SPARCC and LEI) by visit - in treatment period 1 (non-responder imputation) (Combined SPARCC and LEI Subset) Enthesitis, also called enthesopathy, is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Combined SPARCC and LEI Subset: The LEI and SPARCC Subset comprises patients who have an enthesitis score >= 1 when sites from LEI and SPARCC are assessed together at baseline.

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection
Measure Participants	74	76	39
Number [percentage of participants]	62.16 60.3%	59.21 57.5%	82.05 157.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1
	Comments	secukinumab 300mg s.c. injection, 16 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0338
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of presence of enthesitis (SPARCC and LEI) in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95%; 0.13 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2
	Comments	secukinumab 150mg s.c. injection, 16 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0359
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of presence of enthesitis (SPARCC and LEI) in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.36
	Confidence Interval	(2-Sided) 95%; 0.14 to 0.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Patients Achieving ACR50 Response Criteria on Secukinumab 300 or 150 mg vs. Placebo at Week 16
Description	A patient was considered as improved according the ACR50 criteria if she/he had at least 50% improvement in the two of the following measures: Tender joint count, Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity,Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR) Statistical analysis (logistic regression) of ACR50 response by visit - in treatment period 1 (non-responder imputation) (Full Analysis Set) Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) includes all patients assigned study medication. Patients inappropriately randomized (e.g., IRT was called in error for randomization of a screen failed patient) were excluded from analysis set. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned at randomization.

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection
Measure Participants	103	103	3
Number [percentage of participants]	28.16 27.3%	24.27 23.6%	5.77 11.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1
	Comments	secukinumab 300mg s.c. injection, week 16
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0038
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of ACR50 response in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	6.30
	Confidence Interval	(2-Sided) 95%; 1.81 to 21.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2
	Comments	secukinumab 150 mg s.c. injection, week 16
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0149
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of ACR50 response by visit in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.77
	Confidence Interval	(2-Sided) 95%; 1.36 to 16.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Patients Achieving ACR70 Response Criteria on Secukinumab 300 or 150 mg vs. Placebo at Week 16
Description	A patient was considered as improved according the ACR70 criteria if she/he had at least 70% improvement in the two of the following measures: Tender joint count, Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity,Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR) Statistical analysis (logistic regression) of ACR70 response by visit - in treatment period 1 (non-responder imputation) Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) includes all patients assigned study medication. Patients inappropriately randomized (e.g., IRT was called in error for randomization of a screen failed patient) were excluded from analysis set. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned at randomization.

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection
Measure Participants	103	103	52
Number [percentage of participants]	17.48 17%	10.68 10.4%	1.92 3.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1
	Comments	secukinumab 300mg s.c. injection, week 16
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0243
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of ACR70 response in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	10.50
	Confidence Interval	(2-Sided) 95%; 1.36 to 81.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2
	Comments	secukinumab 150 mg s.c. injection, week 16
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1120
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of ACR70 response by visit in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.42
	Confidence Interval	(2-Sided) 95%; 0.67 to 43.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Patients Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Week 16
Description	A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Psoriasis Subset: The psoriasis subset comprises patients having Body Surface Area (BSA) >= 3% at baseline

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection
Measure Participants	79	83	43
Number [percentage of participants]	64.56 62.7%	54.22 52.6%	16.28 31.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1
	Comments	secukinumab 300 mg s.c. injection, week 16
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of PASI75 response by visit in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	9.49
	Confidence Interval	(2-Sided) 95%; 3.73 to 24.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2
	Comments	secukinumab 150 mg s.c. injection, week 16
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of PASI75 response by visit - in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	6.38
	Confidence Interval	(2-Sided) 95%; 2.51 to 16.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Patients Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Week 16
Description	A 90% reduction in the Psoriasis Area and Severity Index score (PASI 90) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Psoriasis Subset: The psoriasis subset comprises patients having Body Surface Area (BSA) >= 3% at baseline

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection
Measure Participants	79	83	43
Number [percentage of participants]	49.37 47.9%	36.14 35.1%	9.3 17.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1
	Comments	secukinumab 300 mg s.c. injection, week 16
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of PASI90 response in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	9.86
	Confidence Interval	(2-Sided) 95%; 3.19 to 30.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2
	Comments	secukinumab 150 mg s.c. injection, week 16
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0043
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of PASI90 response in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.21
	Confidence Interval	(2-Sided) 95%; 1.68 to 16.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Patients Achieving a PASI100 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Week 16
Description	A 100% reduction in the Psoriasis Area and Severity Index score (PASI 100) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis. Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Psoriasis Subset: The psoriasis subset comprises patients having Body Surface Area (BSA) >= 3% at baseline

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection
Measure Participants	79	83	43
Number [percentage of participants]	25.32 24.6%	18.07 17.5%	2.33 4.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1
	Comments	secukinumab 300 mg s.c. injection, week 16
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0107
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of PASI100 response by visit in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	14.38
	Confidence Interval	(2-Sided) 95%; 1.86 to 111.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2
	Comments	secukinumab 150 mg s.c. injection, week 16
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0307
	Comments
	Method	Regression, Logistic
	Comments	Statistical analysis (logistic regression) of PAS100 response by in treatment period 1 (non-responder imputation)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	9.82
	Confidence Interval	(2-Sided) 95%; 1.24 to 77.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline to Week 16 in DAS28-CRP
Description	DAS-CRP uses the C-Reactive Protein (CRP) value. Disease Activity Score (DAS28-CRP) values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28-CRP below the value of 2.6 is interpreted as Remission. DAS28-CRP uses 28 different joints for its calculation: proximal interphalangeal joints (10 joints) metacarpophalangeal joints (10) wrists (2) elbows (2) shoulders (2) knees (2) With the above mentioned parameters. Least squares mean (LSM), Least squares mean (LSM) treatment difference, 95% confidence interval (CI) for treatment difference, and p-values are from an analysis of covariance (ANCOVA) model with treatment (3 treatment groups), baseline DAS28-CRP score, methotrexate usage at baseline (yes, no), and body weight(kg) as explanatory variables.
Time Frame	baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) includes all patients assigned study medication. Patients inappropriately randomized (e.g., IRT was called in error for randomization of a screen failed patient) were excluded from analysis set. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned at randomization.

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection
Measure Participants	103	103	52
Least Squares Mean (Standard Deviation) [scores on a scale]	-1.39 (0.120)	-1.18 (0.125)	-0.35 (0.170)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1
	Comments	secukinumab 300mg s.c. injection, 16 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANCOVA
	Comments	Statistical analysis (ANCOVA) of change from baseline in DAS28-CRP score in treatment period 1 (LOCF)
Method of Estimation	Estimation Parameter	LS Mean of Treatment Difference
	Estimated Value	-1.05
	Confidence Interval	(2-Sided) 95%; -1.45 to -0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Standard Error of Treatment Difference 0.203

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2
	Comments	secukinumab 150 mg s.c. injection
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANCOVA
	Comments	Statistical analysis (ANCOVA) of change from baseline in DAS28-CRP score in treatment period 1 (LOCF)
Method of Estimation	Estimation Parameter	LS Means of Treatment Difference
	Estimated Value	-0.83
	Confidence Interval	(2-Sided) 95%; -1.24 to -0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		LS Mean of Treatment Difference 0.207

12. Secondary Outcome

Title	Change From Baseline to Week 16 in HAQ-DI
Description	The Health assessment questionnaire disability index (HAQ-DI) is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area). The average score across the functional areas yields an overall HAQ score which ranges from 0 (no disability) to 3 (completely disabled).
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) includes all patients assigned study medication. Patients inappropriately randomized (e.g., IRT was called in error for randomization of a screen failed patient) were excluded from analysis set. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned at randomization.

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection	Placebo s.c. injection
Measure Participants	101	101	50
Least Squares Mean (95% Confidence Interval) [scores on a scale]	-0.32	-0.24	-0.11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1
	Comments	secukinumab 300mg s.c. injection
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0107
	Comments
	Method	ANCOVA
	Comments	Statistical analysis (ANCOVA) of change from baseline in HAQ-DI score by in treatment period 1 (LOCF)
Method of Estimation	Estimation Parameter	LS Mean of Treatment Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.37 to -0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Standard Error of Treatment Difference 0.081

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2
	Comments
	Type of Statistical Test	Superiority
	Comments	secukinumab 150 mg s.c. injection
Statistical Test of Hypothesis	p-Value	0.1109
	Comments
	Method	ANCOVA
	Comments	Statistical analysis (ANCOVA) of change from baseline in HAQ-DI score by visit - in treatment period 1 (LOCF)
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Standard Error of Treatment Difference -0.083

13. Other Pre-specified Outcome

Title	Number and Percentage of Patients With ACR20 Response by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)
Description	Exploratory The ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP)
Time Frame	up to 52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Group 1	Group 2	Group 3	Group 4	Group 5
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection (R) Responders	secukinumab 150 mg s.c. injection (NR) Non-responders	Any Secukinumab 150mg	Placebo s.c. injection 300mg
Measure Participants	103	50	42	103	52
week 1	17.48 17%	8.00 7.8%	4.76 9.2%	5.83 2.3%	1.92 NaN
week 16	51.46 50%	72.00 69.9%	4.76 9.2%	36.89 14.3%	23.08 NaN
week 52	47.57 46.2%	68.00 66%	28.57 54.9%	44.66 17.3%	42.31 NaN

14. Other Pre-specified Outcome

Title	Number and Percentage of Patients With ACR50, ACR70 Response by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)
Description	Exploratory
Time Frame	up to 52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Group 1	Group 2	Group 3	Group 4	Group 5
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection (R) Responders	secukinumab 150 mg s.c. injection (NR) Non-responders	Any Secukinumab 150mg	Placebo s.c. injection 300mg
Measure Participants	103	50	42	103	52
ACR50 - week 1	2.91 2.8%	2.38 2.3%	.97 1.9%
ACR50 - week 16	28.16 27.3%	46.00 44.7%	4.76 9.2%	24.27 9.4%	5.77 NaN
ACR70 - week 16	17.48 17%	22.00 21.4%	10.68 20.5%	1.92 0.7%
ACR50 - week 52	32.04 31.1%	48.00 46.6%	14.29 27.5%	29.13 11.3%	17.31 NaN
ACR70 - week 52	21.36 20.7%	28.00 27.2%	4.76 9.2%	15.53 6%	5.77 NaN

15. Other Pre-specified Outcome

Title	Number and Percentage of Patients With Presence of Dactylitis by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)
Description	Exploratory
Time Frame	up to 52 weeks

Outcome Measure Data

Analysis Population Description

Dactylitis Subset The Dactylitis Subset comprised patients who had LDI ≥1 at baseline.

Arm/Group Title	Group 1	Group 2	Group 3	Group 4	Group 5
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection (R) Responders	secukinumab 150 mg s.c. injection (NR) Non-responders	Any Secukinumab 150mg	Placebo s.c. injection 300mg
Measure Participants	103	50	42	103	52
week 1	42.72 41.5%	42.00 40.8%	35.71 68.7%	40.78 15.8%	32.69 NaN
week 16	25.24 24.5%	24.00 23.3%	26.19 50.4%	22.33 8.7%	28.85 NaN
week 52	10.68 10.4%	6.00 5.8%	11.90 22.9%	7.77 3%	9.62 NaN

16. Other Pre-specified Outcome

Title	Number and Percentage of Patients With Presence of Enthesitis by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)
Description	Exploratory
Time Frame	up to 52 weeks

Outcome Measure Data

Analysis Population Description

Leeds Enthesitis Index (LEI) Subset: The LEI Subset comprised patients who had LEI ≥1 at baseline.

Arm/Group Title	Group 1	Group 2	Group 3	Group 4	Group 5
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection (R) Responders	secukinumab 150 mg s.c. injection (NR) Non-responders	Any Secukinumab 150mg	Placebo s.c. injection 300mg
Measure Participants	66	33	27	67	34
week 1	84.85 82.4%	66.67 64.7%	88.89 170.9%	77.61 30.1%	79.41 NaN
week 16	56.06 54.4%	24.24 23.5%	77.78 149.6%	52.24 20.2%	82.35 NaN
week 52	53.03 51.5%	36.36 35.3%	66.67 128.2%	53.73 20.8%	61.76 NaN

17. Other Pre-specified Outcome

Title	Number and Percentage of Patients With Minimal Disease Activity Response by Visit in Entire Treatment Period (up to Week 52) (Non-responder Imputation)
Description	Exploratory
Time Frame	up to 52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Group 1	Group 2	Group 3	Group 4	Group 5
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection (R) Responders	secukinumab 150 mg s.c. injection (NR) Non-responders	Any Secukinumab 150mg	Placebo s.c. injection 300mg
Measure Participants	103	50	42	103	52
week 1	0.97 0.9%
week 16	36.36 35.3%	69.70 67.7%	25.93 49.9%	44.78 17.4%	26.47 NaN
week 52	26.21 25.4%	42.00 40.8%	14.29 27.5%	26.21 10.2%	3.85 NaN

18. Other Pre-specified Outcome

Title	Number and Percentage of Patients With PASI75, PASI90 and PASI100 Response by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)
Description	Exploratory
Time Frame	up to 52 weeks

Outcome Measure Data

Analysis Population Description

Psoriasis subset The psoriasis subset comprises patients having Body Surface Area (BSA) >= 3% at baseline

Arm/Group Title	Group 1	Group 2	Group 3	Group 4	Group 5
Arm/Group Description	secukinumab 300mg s.c. injection	secukinumab 150 mg s.c. injection (R) Responders	secukinumab 150 mg s.c. injection (NR) Non-responders	Any Secukinumab 150mg	Placebo s.c. injection 300mg
Measure Participants	79	40	34	83	43
PASI75 - week 1	8.86 8.6%	7.5 7.3%	11.76 22.6%	8.43 3.3%	4.65 NaN
PASI90 - week 1	1.27 1.2%	2.94 2.9%	1.2 2.3%	1 0.4%
PASI100 - week 1	2.33 2.3%
PASI75 - week 16	64.56 62.7%	80.00 77.7%	38.24 73.5%	54.22 21%	16.28 NaN
PASI90 - week 16	49.37 47.9%	60.00 58.3%	17.65 33.9%	36.14 14%	9.30 NaN
PASI100 - week 16	25.32 24.6%	37.50 36.4%	18.07 34.8%	2.33 0.9%
PASI75 - week 52	67.09 65.1%	77.50 75.2%	52.94 101.8%	59.04 22.9%	53.49 NaN
PASI90- week 52	48.10 46.7%	67.50 65.5%	35.29 67.9%	46.99 18.2%	44.19 NaN
PASI100 - week 52	31.65 30.7%	55.00 53.4%	26.47 50.9%	37.35 14.5%	32.56 NaN

Adverse Events

Time Frame	Adverse events (AE) were collected from first dose of study treatment until end of study treatment up to maximum duration of 52 weeks plus 12 weeks follow up
Adverse Event Reporting Description	An AE is any untoward sign or symptom that occurs in >=5% of participants during study treatment. AEs were counted based on the last actual dose received prior to onset of the AE. The secukinumab 300mg group included patients who received secukinumab 300mg for the entire study and those who switched to secukinumab 300mg in Treatment Period 2
Arm/Group Title	Secukinumab 300mg		Secukinumab 150mg		Placebo
Arm/Group Description	Secukinumab 300mg		Secukinumab 150mg		Placebo
All Cause Mortality
	Secukinumab 300mg		Secukinumab 150mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/191 (0%)		0/103 (0%)		1/52 (1.9%)
Serious Adverse Events
	Secukinumab 300mg		Secukinumab 150mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/191 (7.9%)		4/103 (3.9%)		3/52 (5.8%)
Cardiac disorders
Atrial fibrillation	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Bradycardia	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Cardiac arrest	0/191 (0%)		0/103 (0%)		1/52 (1.9%)
Myocardial infarction	0/191 (0%)		1/103 (1%)		0/52 (0%)
Gastrointestinal disorders
Abdominal pain	0/191 (0%)		0/103 (0%)		1/52 (1.9%)
Diarrhoea	0/191 (0%)		0/103 (0%)		1/52 (1.9%)
Diverticular perforation	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Pancreatitis acute	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
General disorders
Asthenia	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Non-cardiac chest pain	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Infections and infestations
Atypical pneumonia	0/191 (0%)		0/103 (0%)		1/52 (1.9%)
Bronchitis	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Bursitis infective	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Cellulitis	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Diverticulitis	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Intestinal sepsis	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Meningitis aseptic	0/191 (0%)		1/103 (1%)		0/52 (0%)
Pneumonia	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Injury, poisoning and procedural complications
Contusion	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Foot fracture	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Lower limb fracture	0/191 (0%)		1/103 (1%)		0/52 (0%)
Metabolism and nutrition disorders
Dehydration	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Gout	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Musculoskeletal and connective tissue disorders
Arthritis	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Pubic pain	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Spondylitis	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Prostate cancer	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Nervous system disorders
Cerebral cyst	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Ischaemic stroke	0/191 (0%)		0/103 (0%)		1/52 (1.9%)
Seizure	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Syncope	1/191 (0.5%)		1/103 (1%)		0/52 (0%)
Product Issues
Device loosening	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Renal and urinary disorders
Acute kidney injury	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/191 (0.5%)		1/103 (1%)		0/52 (0%)
Dyspnoea	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Pulmonary thrombosis	0/191 (0%)		1/103 (1%)		0/52 (0%)
Skin and subcutaneous tissue disorders
Rash	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Vascular disorders
Deep vein thrombosis	1/191 (0.5%)		0/103 (0%)		0/52 (0%)
Thrombosis	0/191 (0%)		1/103 (1%)		0/52 (0%)
Other (Not Including Serious) Adverse Events
	Secukinumab 300mg		Secukinumab 150mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/191 (34.6%)		35/103 (34%)		12/52 (23.1%)
Gastrointestinal disorders
Diarrhoea	11/191 (5.8%)		7/103 (6.8%)		2/52 (3.8%)
Infections and infestations
Bronchitis	10/191 (5.2%)		1/103 (1%)		1/52 (1.9%)
Nasopharyngitis	6/191 (3.1%)		6/103 (5.8%)		1/52 (1.9%)
Sinusitis	8/191 (4.2%)		3/103 (2.9%)		4/52 (7.7%)
Upper respiratory tract infection	26/191 (13.6%)		6/103 (5.8%)		1/52 (1.9%)
Urinary tract infection	10/191 (5.2%)		5/103 (4.9%)		0/52 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/191 (4.7%)		3/103 (2.9%)		4/52 (7.7%)
Back pain	10/191 (5.2%)		8/103 (7.8%)		8/52 (15.4%)
Musculoskeletal pain	6/191 (3.1%)		1/103 (1%)		3/52 (5.8%)
Pain in extremity	3/191 (1.6%)		5/103 (4.9%)		3/52 (5.8%)
Psoriatic arthropathy	3/191 (1.6%)		6/103 (5.8%)		0/52 (0%)
Vascular disorders
Hypertension	8/191 (4.2%)		6/103 (5.8%)		0/52 (0%)

Limitations/Caveats

Period 2 (week 16 up to 52 weeks) contained only exploratory outcomes. AEs are presented cumulitively

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.