Trial Outcomes & Findings for Efficacy of Secukinumab Compared to Adalimumab in Patients With Psoriatic Arthritis (NCT NCT02745080)

Last Updated: 2021-01-27

Results Overview

Clinical response, failure to permanently discontinue study medication prematurely, and lack of need for rescue medication was required for a patient to achieve treatment success. The primary endpoint is the proportion of patients with monotherapy ACR20 response at Week 52 where monotherapy ACR20 response is defined as meeting the following 3 conditions: 1. achieving American College of Rheumatology 20 (ACR20) response 2. no permanent study treatment (secukinumab or adalimumab) discontinuation before or at Week 50 (the last dosing visit) 3. no use of conventional disease modifying anti-rheumatic drugs (also known as non-biologic DMARDs) cDMARDs (including Methotrexate (MTX)) after Week 36 (regardless of the starting time of taking cDMARDs)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

853 participants

Primary outcome timeframe

Week 52

Results posted on

2021-01-27

Participant Flow

This study was conducted at 161 centers in 26 countries worldwide: Australia, Bulgaria, Canada, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, India, Israel, Italy, South Korea, Latvia, Lithuania, The Netherlands, Poland, Portugal, Russia, Slovakia, Spain, UK and USA.

853 patients were randomized in a 1:1 ratio to receive secukinumab 300 mg (N=426) or adalimumab 40 mg (N=427); All randomized patients were analyzed for efficacy and safety.

Participant milestones

Participant milestones
Measure	Secukinumab 300 mg s.c. Secukinumab 300 mg administered at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 48.	Adalimumab 40 mg s.c. Adalimumab 40 mg administered at Baseline followed by dosing every 2 weeks until Week 50.
Overall Study STARTED	426	427
Overall Study COMPLETED	371	338
Overall Study NOT COMPLETED	55	89

Reasons for withdrawal

Reasons for withdrawal
Measure	Secukinumab 300 mg s.c. Secukinumab 300 mg administered at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 48.	Adalimumab 40 mg s.c. Adalimumab 40 mg administered at Baseline followed by dosing every 2 weeks until Week 50.
Overall Study Adverse Event	13	21
Overall Study Lack of Efficacy	11	23
Overall Study Lost to Follow-up	3	3
Overall Study Physician Decision	3	0
Overall Study Protocol Violation	3	1
Overall Study Withdrawal by Subject	22	41

Baseline Characteristics

Efficacy of Secukinumab Compared to Adalimumab in Patients With Psoriatic Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Secukinumab 300 mg s.c. n=426 Participants Secukinumab 300 mg administered at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 48.	Adalimumab 40 mg s.c. n=427 Participants Adalimumab 40 mg administered at Baseline followed by dosing every 2 weeks until Week 50.	Total n=853 Participants Total of all reporting groups
Age, Continuous	48.5 Years STANDARD_DEVIATION 12.38 • n=5 Participants	49.5 Years STANDARD_DEVIATION 12.44 • n=7 Participants	49.0 Years STANDARD_DEVIATION 12.41 • n=5 Participants
Sex: Female, Male Female	218 Participants n=5 Participants	198 Participants n=7 Participants	416 Participants n=5 Participants
Sex: Female, Male Male	208 Participants n=5 Participants	229 Participants n=7 Participants	437 Participants n=5 Participants
Race/Ethnicity, Customized Asian	16 Participants n=5 Participants	20 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	402 Participants n=5 Participants	391 Participants n=7 Participants	793 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 52

Population: Full Analysis Set (FAS)

Outcome measures

Outcome measures
Measure	Secukinumab 300 mg s.c. n=426 Participants Secukinumab 300 mg administered at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 48.	Adalimumab 40 mg s.c. n=427 Participants Adalimumab 40 mg administered at Baseline followed by dosing every 2 weeks until Week 50.
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Week 52	67.4 Percentage of Participants Interval 62.8 to 71.7	61.5 Percentage of Participants Interval 56.8 to 66.0

SECONDARY outcome

Timeframe: Week 52

Population: Psoriasis Subset of the Full Analysis Set (FAS)

The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents participants who achieved at least a 90 percent improvement from baseline in the PASI score.

Outcome measures

Outcome measures
Measure	Secukinumab 300 mg s.c. n=215 Participants Secukinumab 300 mg administered at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 48.	Adalimumab 40 mg s.c. n=202 Participants Adalimumab 40 mg administered at Baseline followed by dosing every 2 weeks until Week 50.
Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI)-90 Response at Week 52	65.4 Percentage of Participants Interval 58.8 to 71.5	43.2 Percentage of Participants Interval 36.5 to 50.2

SECONDARY outcome

Timeframe: Week 52

Population: Full Analysis Set (FAS)

Clinical response, failure to permanently discontinue study medication prematurely, and lack of need for rescue medication was required for a patient to achieve treatment success. The secondary endpoint is the proportion of patients with monotherapy ACR50 response at Week 52 where monotherapy ACR50 response is defined as meeting the following 3 conditions: 1. achieving American College of Rheumatology 50 (ACR50) response 2. no permanent study treatment (secukinumab or adalimumab) discontinuation before or at Week 52 3. no use of conventional disease modifying anti-rheumatic drugs (also known as non-biologic DMARDs) cDMARDs (including Methotrexate (MTX)) after Week 36 (regardless of the starting time of taking cDMARDs)

Outcome measures

Outcome measures
Measure	Secukinumab 300 mg s.c. n=426 Participants Secukinumab 300 mg administered at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 48.	Adalimumab 40 mg s.c. n=427 Participants Adalimumab 40 mg administered at Baseline followed by dosing every 2 weeks until Week 50.
Percentage of Participants Who Achieved an American College of Rheumatology 50% (ACR50) Response at Week 52	49.0 Percentage of Participants Interval 44.3 to 53.7	44.8 Percentage of Participants Interval 40.1 to 49.5

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full Analysis Set (FAS)

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

Outcome measures

Outcome measures
Measure	Secukinumab 300 mg s.c. n=426 Participants Secukinumab 300 mg administered at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 48.	Adalimumab 40 mg s.c. n=427 Participants Adalimumab 40 mg administered at Baseline followed by dosing every 2 weeks until Week 50.
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI Score) at Week 52	-0.58 Unit on a scale Standard Error 0.027	-0.56 Unit on a scale Standard Error 0.027

SECONDARY outcome

Timeframe: Week 52

Population: Enthesitis Subset (LEI) of the Full Analysis Set (FAS)

Enthesitis refers to inflammation of entheses, the site where ligaments or tendons insert into the bones. Resolution was defined as the absence of recorded enthesitis; conducted by the study assessor.

Outcome measures

Outcome measures
Measure	Secukinumab 300 mg s.c. n=234 Participants Secukinumab 300 mg administered at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 48.	Adalimumab 40 mg s.c. n=264 Participants Adalimumab 40 mg administered at Baseline followed by dosing every 2 weeks until Week 50.
Percentage of Participants Who Achieved Resolution of Enthesitis at Week 52	60.5 Percentage of Participants Interval 54.1 to 66.6	54.2 Percentage of Participants Interval 48.2 to 60.2

Adverse Events

AIN457 300 mg

Serious events: 37 serious events

Other events: 226 other events

Deaths: 1 deaths

Adalimumab 40 mg

Serious events: 36 serious events

Other events: 236 other events

Deaths: 0 deaths

Total

Serious events: 73 serious events

Other events: 462 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	AIN457 300 mg n=426 participants at risk Secukinumab 300 mg administered at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 48.	Adalimumab 40 mg n=427 participants at risk Adalimumab 40 mg administered at Baseline followed by dosing every 2 weeks until Week 50.	Total n=853 participants at risk Total
Gastrointestinal disorders Diarrhoea	7.5% 32/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	8.7% 37/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	8.1% 69/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.
General disorders Injection site reaction	0.94% 4/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	6.6% 28/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	3.8% 32/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.
Infections and infestations Bronchitis	3.8% 16/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	6.3% 27/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	5.0% 43/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.
Infections and infestations Nasopharyngitis	20.7% 88/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	19.7% 84/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	20.2% 172/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.
Infections and infestations Upper respiratory tract infection	9.9% 42/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	12.6% 54/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	11.3% 96/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.
Musculoskeletal and connective tissue disorders Arthralgia	6.8% 29/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	7.3% 31/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	7.0% 60/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.
Musculoskeletal and connective tissue disorders Back pain	4.0% 17/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	7.3% 31/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	5.6% 48/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.
Musculoskeletal and connective tissue disorders Psoriatic arthropathy	8.0% 34/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	8.9% 38/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	8.4% 72/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.
Nervous system disorders Headache	8.5% 36/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	7.7% 33/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	8.1% 69/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 24/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	3.3% 14/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	4.5% 38/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.9% 25/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	3.5% 15/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	4.7% 40/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.
Skin and subcutaneous tissue disorders Psoriasis	7.7% 33/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	8.0% 34/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	7.9% 67/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.
Vascular disorders Hypertension	6.3% 27/426 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	5.6% 24/427 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.	6.0% 51/853 • Treatment emergent adverse events were collected from first dose of study treatment until 12 Weeks (84 days) following the last administration of study treatment, an average of 68 weeks. Any sign or symptom that occurs during the study treatment plus the 30 days post-treatment.

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