Trial Outcomes & Findings for Efficacy and Safety of Etanercept in Active RA Despite Methotrexate Therapy in Japan (NCT NCT00688103)

NCT ID: NCT00688103

Last Updated: 2015-10-01

Results Overview

EULAR good response was defined as reaching, at least, low decease activity by the disease activity score of 28 joints (DAS28) and its improvement by \> 1.2. DAS28 is a quantitative composite measure of disease activity for rheumatoid arthritis, and DAS28 \< 3.2 is regarded as low disease activity.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 151 participants
• Primary outcome timeframe: at 24 weeks
• Results posted on: 2015-10-01

Participant Flow

Participant milestones

Measure	ETN Alone Etanercept alone treatment group (25mg, twice/week, s.c.)	ETN+MTX Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)
Overall Study STARTED	74	77
Overall Study Actually Treated	71	76
Overall Study COMPLETED	44	64
Overall Study NOT COMPLETED	30	13

Reasons for withdrawal

Measure	ETN Alone Etanercept alone treatment group (25mg, twice/week, s.c.)	ETN+MTX Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)
Overall Study Adverse Event	4	1
Overall Study Lack of Efficacy	11	1
Overall Study Withdrawal by Subject	4	2
Overall Study complex reasons	11	9

Baseline Characteristics

Efficacy and Safety of Etanercept in Active RA Despite Methotrexate Therapy in Japan

Baseline characteristics by cohort

Measure	ETN Alone n=74 Participants Etanercept alone treatment group (25mg, twice/week, s.c.)	ETN+MTX n=77 Participants Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)	Total n=151 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	54 Participants n=93 Participants	58 Participants n=4 Participants	112 Participants n=27 Participants
Age, Categorical >=65 years	20 Participants n=93 Participants	19 Participants n=4 Participants	39 Participants n=27 Participants
Age, Continuous	58.1 years STANDARD_DEVIATION 12.6 • n=93 Participants	56.6 years STANDARD_DEVIATION 11.1 • n=4 Participants	57.3 years STANDARD_DEVIATION 10.2 • n=27 Participants
Sex: Female, Male Female	65 Participants n=93 Participants	62 Participants n=4 Participants	127 Participants n=27 Participants
Sex: Female, Male Male	9 Participants n=93 Participants	15 Participants n=4 Participants	24 Participants n=27 Participants
Region of Enrollment Japan	74 participants n=93 Participants	77 participants n=4 Participants	151 participants n=27 Participants

PRIMARY outcome

Timeframe: at 24 weeks

EULAR good response was defined as reaching, at least, low decease activity by the disease activity score of 28 joints (DAS28) and its improvement by > 1.2. DAS28 is a quantitative composite measure of disease activity for rheumatoid arthritis, and DAS28 < 3.2 is regarded as low disease activity.

Outcome measures

Measure	ETN Alone n=69 Participants Etanercept alone treatment group (25mg, twice/week, s.c.)	ETN+MTX n=73 Participants Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)
EULAR Good Response	33.3 percentage of responders	52.1 percentage of responders

PRIMARY outcome

Timeframe: at 24 weeks

ACR (American College of Rheumatology) 50 response is defined by the following definition of improvement: at least 50% improvement in tender and swollen joint counts and at least 50% improvement in 3 of the 5 remaining ACR-core set measures; patient and physician global assessments, pain, disability, and an acute phase reactant (erythrocyte sedimentation rate or C-reactive protein).

Outcome measures

Measure	ETN Alone n=69 Participants Etanercept alone treatment group (25mg, twice/week, s.c.)	ETN+MTX n=73 Participants Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)
ACR50 Response Rate	47.8 percentage of responders	64.4 percentage of responders

PRIMARY outcome

Timeframe: at 52 weeks

The van der Heijde-modifiedtotal Sharp score is the sum of scores for erosions and joint space narrowing. The minimum and maximum total scores are 0 and 448, respectively. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively.

Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet.

For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, <50% of the original joint space; 3=general, >50% of the original joint space or subluxation; 4=ankylosis.

Outcome measures

Measure	ETN Alone n=53 Participants Etanercept alone treatment group (25mg, twice/week, s.c.)	ETN+MTX n=68 Participants Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)
Radiographic Progression Defined by Change in Van Der Heijde-modified Total Sharp Score	3.6 units on a scale Standard Deviation 10.4	0.8 units on a scale Standard Deviation 6.4

Adverse Events

ETN Alone

Serious events: 2 serious events

Other events: 34 other events

Deaths: 0 deaths

ETN+MTX

Serious events: 9 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Measure	ETN Alone n=71 participants at risk Etanercept alone treatment group (25mg, twice/week, s.c.)	ETN+MTX n=76 participants at risk Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)
Musculoskeletal and connective tissue disorders bone fracture	2.8% 2/71 • Number of events 2	5.3% 4/76 • Number of events 4
Infections and infestations Herpes Zoster	0.00% 0/71	2.6% 2/76 • Number of events 2
Cardiac disorders congestive heart failure	0.00% 0/71	1.3% 1/76 • Number of events 1
Infections and infestations cellulitis	0.00% 0/71	1.3% 1/76 • Number of events 1
Nervous system disorders brain hemorrhage	0.00% 0/71	1.3% 1/76 • Number of events 1
Metabolism and nutrition disorders mammary carcinoma	0.00% 0/71	1.3% 1/76 • Number of events 1

Other adverse events

Measure	ETN Alone n=71 participants at risk Etanercept alone treatment group (25mg, twice/week, s.c.)	ETN+MTX n=76 participants at risk Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)
Infections and infestations upper airway viral infection	40.8% 29/71 • Number of events 55	43.4% 33/76 • Number of events 55
Gastrointestinal disorders gastroentelitis	9.9% 7/71 • Number of events 7	10.5% 8/76 • Number of events 8
General disorders injection site reaction	22.5% 16/71 • Number of events 16	11.8% 9/76 • Number of events 9
Skin and subcutaneous tissue disorders rash	26.8% 19/71 • Number of events 19	10.5% 8/76 • Number of events 8
Injury, poisoning and procedural complications mild injury	7.0% 5/71 • Number of events 5	5.3% 4/76 • Number of events 4
Nervous system disorders headache	5.6% 4/71 • Number of events 4	3.9% 3/76 • Number of events 3

Additional Information

Dr. Hideto Kameda

School of Medicine, Toho University

Phone: +81-3-3468-1251

Email: hideto.kameda@med.toho-u.ac.jp

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place